The DOI matches its Crossref record; 414 of the 421 references it cites were found in a registry or an index; none of the 237 sources its claims cite is checked for support yet.
Anxiety, Depression, and the Microbiome: A Role for Gut Peptides
Open accessAbstract
The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.
Overview
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Written from the paper’s full text.
TL;DR
This narrative review proposes that gut-derived peptides are key mediators of microbiota–gut–brain signaling in anxiety and depression. It synthesizes evidence that microbiota composition and microbial metabolites alter peptides such as NPY, PYY, PP, GLP-1, CCK, ghrelin, CRF, and oxytocin, with psychobiotics suggested as a future therapeutic route.
Key findings
- The gastrointestinal tract is described as the largest endocrine organ in mammals, with enteroendocrine cells representing no more than 1% of the total gut epithelium cell population and releasing more than 20 signaling molecules. The review argues these gut peptides can signal to the brain via immune cells, vagus nerve terminals, and the bloodstream.
- Microbiota manipulations are reported to alter gut peptides: germ-free mice, antibiotic-treated mice, and animals given probiotics or prebiotics show increases in NPY and PYY and increases in GLP-1; germ-free mice show decreased CCK and ghrelin; fasted germ-free mice show increased ghrelin; antibiotic treatment from adolescence decreases oxytocin without changing CRF; and *Lactobacillus reuteri* increases oxytocin.
- GLP-1 is reported to be rapidly degraded, with <10% of secreted GLP-1 reaching systemic circulation. The review notes that GLP-1 receptor agonists blunt anxiety-like behavior in diabetic mice, promote antidepressant-like effects in rodents, and a 4-week GLP-1 agonist treatment reverted cognitive deficits in patients with mood disorders without affecting metabolic parameters.
- PP is about 100 times more potent than NPY in activating Y4 receptors, and the review suggests PP/Y4 signaling may be an important gut–brain route in anxiety and depression. CCK levels are positively correlated with increased anxiety-like behavior in human and rodent studies, while ghrelin and CRF are discussed as modulators of stress, fear, and depressive-like phenotypes.
Methods
- Design: narrative review of the microbiota–gut–brain axis, focusing on gut peptides as signaling molecules in anxiety and depression.
- Data/sample: synthesis of preclinical animal studies, germ-free and antibiotic-treated rodent models, probiotic/prebiotic interventions, human cohort data, and human clinical trials cited in the reference list.
- Main analysis: thematic discussion of peptide families and systems—NPY/PYY/PP, GLP-1, CCK, ghrelin, CRF, and oxytocin—and their interactions with gut microbiota, immune signaling, vagal pathways, and psychobiotic strategies.
Limitations
- The paper states that mechanisms underlying enteroendocrine cell–microbiota interactions have yet to be fully resolved, that a direct link between the gut microbiota and ghrelin modulation remains absent, that more studies linking PYY changes and the gut microbiota are needed, and that additional studies are needed to demonstrate a functional role of the gut microbiota in the host oxytocin system.
- The paper states we are at very early stages of understanding microbiota–gut–brain communication.
- Evident from the text: this is a narrative review rather than a systematic review or meta-analysis; many findings are from animal models or correlative human data, and the review notes interspecies variability and contrasting results between humans and animals, so causal direction is often not established.
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Claims the paper makes
147 Not checked yet · 33 Own interpretation · 2 No basis given
In the paper
“It is now also becoming clear that the activity of EECs, which represent no more than 1% of the total gut epithelium cell population, is modulated by the gut microbiota [2][3][4].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Introduction
What the sources say
- Not checked yetcites [2][3][4]
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Enteric bacterial diversity and composition uniquely influence the release of gut peptides, including glucagon-like peptide (GLP-1), peptide YY (PYY), cholecystokinin (CCK), corticotropin-releasing factor (CRF), oxytocin, and ghrelin [1,[5][6][7].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Introduction
What the sources say
- Not checked yetcites [1,[5][6][7]
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication.”
- Also stated in: § Gut peptide receptor · hedged
“Following secretion, gut peptides diffuse throughout the lamina propria, which is occupied by a variety of immune cells, ultimately to reach the bloodstream, to stimulate sensory neurons and potentially to act on the vagus nerve, thereby creating an intersection for gut peptidergic signaling to the brain [111].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Abstract
What the sources say
- Not checked yetcites [111] Okano-Matsumoto, 2011, Electrophysiological evidence for distinct vagal pathways mediating CCK-evoked motor effects in the proximal versus distal stomach, J Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Gut peptide receptor · hedged
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For the peptides discussed in this review, beyond the role in satiety, they can be stimulated by bacterial products that come into contact with the gut epithelium [83,105,106].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut peptide receptor
What the sources say
- Not checked yetcites [83] Tolhurst, 2012, Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2, Diabetes source
- Not checked yetcites [105] Lin, 2012, Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms, PLOS ONE
- Not checked yetcites [106] Gao, 2009, Butyrate improves insulin sensitivity and increases energy expenditure in mice, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Recent data from human cohorts support preclinical findings suggesting that the modulation of the gut microbiota can influence brain function [49][50][51][52][53].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Introduction
What the sources say
- Not checked yetcites [49][50][51][52][53]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Psychobiotics, which target the gut microbiota to affect mental health for the better, may be one such innovative strategy (for review, see [54][55][56]).”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Introduction
What the sources say
- Not checked yetcites [54][55][56]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Of note, several of the same peptides and their receptors that are released into the gut are also widely expressed in the brain or signal to the brain, where these peptides play well-established roles in the neurobiology of anxiety and depression (for review, see [23,24]).”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Introduction
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Conversely, certain antibiotics, such as β-lactams and tetracyclines have potential antidepressant properties in rodents and humans [161,162].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [161] Ferreira Mello, 2013, Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration, J Psychiatr Res source
- Not checked yetcites [162] Miyaoka, 2012, Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study, Prog Neuropsychopharmacol Biol Psychiatry source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In mice that underwent chronic stress, reductions in the genus Bacteroides were identified [149].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [149] Bailey, 2011, Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation, Brain Behav Immun source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The functional role of the NPY family in gut-brain signaling is supported by the wide distribution of the 4 main NPY receptors in mammals (Y 1 ,Y 2 , Y 4 , and Y 5 receptor) (for a review, see”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Neuropeptide Y Family
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, Maes et al. [142,143] found in 2 different studies that lipopolysaccharide (LPS) produced by gut bacteria could increase immune responses in depressed patients.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [142] Maes, 2012, Increased IgA and IgM responses against gut commensals in chronic depression: Further evidence for increased bacterial translocation or leaky gut, J Affect Disord source
- Not checked yetcites [143] Maes, 2008, The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression, Neuro Endocrinol Lett
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“However, in depressive patients without IBS symptoms, the Firmicutes/Bacteroidetes ratio was inversely correlated with the microbiota composition profiled in patients with IBS [145-147].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [145] Jiang, 2015, Altered fecal microbiota composition in patients with major depressive disorder, Brain Behav Immun source
- Not checked yetcites [146] Naseribafrouei, 2014, Correlation between the human fecal microbiota and depression, Neurogastroenterol Motil source
- Not checked yetcites [147] Kelly, 2016, Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat, J Psychiatr Res source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Epidemiologic studies have suggested that some classes of antibiotics such as fluoroquinolones are associated with the development of depression and anxiety [163][164][165][166].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [163][164][165][166]
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, the manipulation of the gut microbiota may be a useful tool to decode the physiological role of the gut-brain axis in psychiatric disorders [167].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [167] Pinto-Sanchez, 2017, Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome, Gastroenterology source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The Y 4 receptor, which is mainly activated by peripheral PP, modulates anxiety and fear-related disorders in rodents [174,185,186].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [174] Tasan, 2009, Increased novelty-induced motor activity and reduced depression-like behavior in neuropeptide Y (NPY)-Y4 receptor knockout mice, Neuroscience source
- Not checked yetcites [185] Verma, 2016, Hunger promotes fear extinction by activation of an amygdala microcircuit, Neuropsychopharmacology source
- Not checked yetcites [186] Painsipp, 2008, Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4 receptor knockout mice, Genes Brain Behav source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For instance, PYY expression is upregulated in the ileum after treatment with prebiotic galacto-oligosaccharides (GOS) [202].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [202] Hong, 2016, Evaluation of prebiotic effects of high-purity galactooligosaccharides in vitro and in vivo, Food Technol Biotechnol source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, these gut peptides can activate their cognate receptors located in vagal afferents to signal to the brainstem [179,180].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Neuropeptide Y Family
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The expression of NPY in the hypothalamus (where NPY plays a major role in feeding behavior and stress response) is increased in adult, healthy, germ-free mice when compared with conventionally raised mice [116].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [116] Schéle, 2013, The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system, Endocrinology source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“PP is about 100 times more potent than NPY in Y 4 activation, suggesting that PP/Y 4 receptors can be an important route of gut-brain communication in the pathogenesis of anxiety and depression.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“There is abundant evidence that the central NPY system affects stress-related disorders such as anxiety and depression (for a review, see [181,182]).”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Following a meal, PP and PYY are released and inhibit gastric emptying via the targeting of receptors on the intestinal epithelium, as well as vagus nerve signaling [187][188][189].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [187][188][189]
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, PYY secretion is influenced by activation of FFA receptors by SCFA [85,[198][199][200].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [85,[198][199][200]
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A separate study in rodents demonstrated that bacterial proteins produced after nutrient-induced Esherichia coli growth may signal the CNS via increased plasma PYY [205].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [205] Breton, 2016, Gut commensal E. coli proteins activate host satiety pathways following nutrient-induced bacterial growth, Cell Metab source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Correlative evidence exists between PYY and the gut microbiota, where elevation in PYY in obese individuals was associated with changes in the gut microbiota [197].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [197] Liu, 2017, Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome, Front Microbiol
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“However, anxiety-or depression-like behaviors were unaffected in these animals [25].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [25] Fröhlich, 2016, Cognitive impairment by antibiotic-induced gut dysbiosis: analysis of gut microbiota-brain communication, Brain Behav Immun source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, depletion of NPY or PYY in mice prevents the anxiogenic and depressive-like behavior often promoted by colitis [210].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [210] Painsipp, 2011, Sex-dependent control of murine emotional-affective behaviour in health and colitis by peptide YY and neuropeptide Y, Br J Pharmacol source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, it is likely that gut microbiota contributes indirectly to NPY release and signaling to affect its homeostatic role in balancing the brain's response to stress in the brain.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Hong et al. [202] found an upregulation of intestinal PYY with the commensal bacteria Bifidobacterium bifidum in rats.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [202] Hong, 2016, Evaluation of prebiotic effects of high-purity galactooligosaccharides in vitro and in vivo, Food Technol Biotechnol source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Evidence of direct involvement interaction between the NPY system and the gut microbiota modulating behavior is lacking.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However, a study in humans showed that plasma PYY was unaffected after treatment with barley kernel bread, an indigestible carbohydrate source, and a mixture of the probiotics Bifidobacterium animalis, Lactobacillus reuteri, and Lacobacillus plantarum [206].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [206] Nilsson, 2016, Gut microbiota mediated benefits of barley kernel products on metabolism, gut hormones, and inflammatory markers as affected by co-ingestion of commercially available probiotics: a randomized controlled study in healthy subjects, Clin Nutr ESPEN source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, in a colitis disease model, it was found that an increase in the colonic synthesis of NPY was associated with decreased colonic Y 1 receptor expression [208,209].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [208] Chandrasekharan, 2008, Targeted deletion of neuropeptide Y (NPY) modulates experimental colitis, PLOS ONE source
- Not checked yetcites [209] Pang, 2010, Amelioration of dextran sulfate sodium-induced colitis by neuropeptide Y antisense oligodeoxynucleotide, Int J Colorectal Dis source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Germ-free mice usually present an anxiolytic phenotype behaviorally [214].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [214] Luczynski, 2016, Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior, Int J Neuropsychopharmacol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, plasma NPY levels decreased after the introduction of conventional intestinal microbiota in germ-free mice [217], a shift also observed by Sudo et al. [216] with the corticosterone levels after recolonization of germ-free mice.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [217] Husebye, 2001, Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats, Am J Physiol Gastrointest Liver Physiol source
- Not checked yetcites [216] Sudo, 2004, Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice, J Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, Schéle et al. [116] demonstrated the role of NPY in counteracting the increased plasma levels of corticosterone in germ-free rodents.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [116] Schéle, 2013, The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system, Endocrinology source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Following release into the bloodstream, GLP-1 is rapidly degraded, resulting in < 10% of secreted GLP-1 reaching systemic circulation as a result of enzymatic degradation [221].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > GLP-1
What the sources say
- Not checked yetcites [221] Holst, 2007, The physiology of glucagon-like peptide 1, Physiol Rev source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, it is likely that GLP-1 acts locally in a paracrine fashion in the intestine.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > GLP-1
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“It is particularly relevant that patients with diabetes are twice as likely to suffer from anxiety and depression than the general population [242,243].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Evidence suggests a key role for SCFA in modulating GLP-1 expression through the stimulation of FFA2 and FFA3 receptors in rodents [83,105,[257][258][259][260].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [83,105,[257][258][259][260]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Both human and rodents studies indicate a positive correlation of CCK levels and increased anxiety-like behavior [273-275].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [273] Del Boca, 2012, Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice, Neuroscience source
- Not checked yetcites [274] Rezayat, 2005, Cholecystokinin and GABA interaction in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety, Physiol Behav source
- Not checked yetcites [275] Desai, 2014, Neuropeptide Y attenuates anxiety- and depression-like effects of cholecystokinin-4 in mice, Neuroscience source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“plasma concentrations of CCK were not different in severely obese patients versus normal-weight individuals [292].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [292] Federico, 2016, Gastrointestinal hormones, intestinal microbiota and metabolic homeostasis in obese patients: effect of bariatric surgery, In Vivo
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The result was observed in glucose-tolerant volunteers, where the daily administration of Lactobacillus reuteri or the commercially available VSL#3 (a formulation with 8 strains of commensal bacteria, including different strains of Bifidobacterium and Lactobacillus) increased GLP-1 release into the blood, without a change in insulin sensitivity or body fat distribution [120, 124].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [120] Yadav, 2013, Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion, J Biol Chem source
- Not checked yetcites [124] Simon, 2015, Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose tolerant humans: a proof of concept, Diabetes Care source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“CCK signaling is also modulated by the gut microbiota.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mice lacking T-cell receptors, which develop inflammation on the colonic epithelium, have been associated with a decrease in the number of EEC cells specialized in secreting CCK [285].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [285] Rubin, 2000, Altered enteroendocrine cell expression in T cell receptor alpha chain knock-out mice, Microsc Res Tech source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, it is likely that attenuation of glucose fluctuations by GLP-1 is responsible for its neuroprotective effects, especially during plasma hyperglycemia.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In healthy volunteers, a mixture of barley kernel bread and Bifidobacterium animalis, Lactobacillus reuteri, and Lactobacillus plantarum increased levels of plasma of GLP-1 without affecting metabolic outcomes [206].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [206] Nilsson, 2016, Gut microbiota mediated benefits of barley kernel products on metabolism, gut hormones, and inflammatory markers as affected by co-ingestion of commercially available probiotics: a randomized controlled study in healthy subjects, Clin Nutr ESPEN source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Mice lacking endogenous ghrelin have a dampened circulating glucocorticoid response following an acute stressor due a deficit in the PVN response needed to stimulate ACTH from the pituitary [295,311].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [295] Spencer, 2012, Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress, Biol Psychiatry source
- Not checked yetcites [311] Spencer, 2015, Ghrelin's role in the hypothalamic-pituitary-adrenal axis stress response: implications for mood disorders, Biol Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Federico et al. [292] did not observe changes in the gut microbiota after obese patients underwent bariatric surgery.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [292] Federico, 2016, Gastrointestinal hormones, intestinal microbiota and metabolic homeostasis in obese patients: effect of bariatric surgery, In Vivo
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, ghrelin may regulate the network designed to enhance survival potential by increasing vigilance, fear, and controlling anxiety.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, germ-free mice have lower levels of plasma ghrelin under basal conditions than conventional mice [128,129].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“However, different stressors, such as social defeat and restraint stress in rodents, can increase long-term ghrelin levels in the stomach [309][310][311].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [309] Lutter, 2008, The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress, Nat Neurosci source
- Not checked yetcites [310] Patterson, 2010, Altered metabolic and neurochemical responses to chronic unpredictable stressors in ghrelin receptor-deficient mice, Eur J Neurosci source
- Not checked yetcites [311] Spencer, 2015, Ghrelin's role in the hypothalamic-pituitary-adrenal axis stress response: implications for mood disorders, Biol Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the regulatory role of ghrelin in the CNS may be affected by the gut microbiota via vagus nerve to the NTS.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Peripherally produced ghrelin exerts its appetite-inducing effects centrally after passing through the BBB [112, 302-304].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Ghrelin
What the sources say
- Not checked yetcites [112] Banks, 2002, Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure, J Pharmacol Exp Ther source
- Not checked yetcites [302] Schaeffer, 2013, Rapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons, Proc Natl Acad Sci U S A source
- Not checked yetcites [303] Cabral, 2013, Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid, Neuroscience source
- Not checked yetcites [304] Banks, 2008, The blood-brain barrier: connecting the gut and the brain, Regul Pept source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Ghrelin is a 28 amino-acid stomach-derived peptide known for its powerful physiological orexigenic and adipogenic effects, as well as for its contribution toward the stress response, anxiety, and depression [293][294][295][296][297].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Ghrelin
What the sources say
- Not checked yetcites [293] Kojima, 1999, Ghrelin is a growth-hormone-releasing acylated peptide from stomach, Nature source
- Not checked yetcites [294] Nakazato, 2001, A role for ghrelin in the central regulation of feeding., Nature source
- Not checked yetcites [295] Spencer, 2012, Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress, Biol Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Taken together, the results from this study show that circulating CCK may not be modulated by changes in the gut microbiome facilitated by alterations in energy metabolism.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [292] Federico, 2016, Gastrointestinal hormones, intestinal microbiota and metabolic homeostasis in obese patients: effect of bariatric surgery, In Vivo
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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None of the sources cited for this claim have been checked yet.
In the paper
“repeated injection of GHS receptor agonists into the amygdala increases stressor-inducing fear memory formation”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [296] Huang, 2017, Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents, Behav Brain Res source
- Not checked yetcites [315] Meyer, 2014, A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear, Mol Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“However, when acute stress reactions become more frequent, it can lead to the development of stress-related disorders, including anxiety and depression (for review, see [329,339]).”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“A negative correlation between Firmicutes and ghrelin levels was observed both in humans and rodents [322,323].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [322] Nilaweera, 2017, Whey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression, Am J Physiol Endocrinol Metab source
- Not checked yetcites [323] Tubbs, 2014, Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance, Diabetes source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, serum ghrelin levels are negatively correlated with the abundance of certain gut bacteria, including the commensal Bifidobacterium and Lactobacillus strains [318].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [318] Queipo-Ortuño, 2013, Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels, PLOS ONE source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, injection of ghrelin in healthy humans increased plasma glucocorticoids levels [326].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [326] Schmid, 2005, Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls, Neuropsychopharmacology source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Bethin et al. [338] found that immune activation induced by endotoxin produced a robust rise in plasma corticosterone in CRF or CRF 1 receptor knockout mice, comparable with wildtype mice.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > CRF
What the sources say
- Not checked yetcites [338] Bethin, 2000, Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation, Proc Natl. Acad Sci U S A source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, oligofructose does not change plasma ghrelin levels in obese rats fed a high fat/high sucrose diet [203].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [203] Cluny, 2015, Interactive effects of oligofructose and obesity predisposition on gut hormones and microbiota in diet-induced obese rats, Obesity source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Functional CRF 1 receptors are essential for the activation of the endocrine response to stress [169].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [169] Alexander, 2011, Guide to receptors and channels (GRAC), 5th edition, Br J Pharmacol source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“In addition, ingestion of conjugated linoleic acid induced changes in the gut microbiota, increasing Bacteroides/Prevotella species and ghrelin levels in the gastric mucosa of mice [319].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [319] Chaplin, 2015, Conjugated linoleic acid supplementation under a high-fat diet modulates stomach protein expression and intestinal microbiota in adult mice, PLOS ONE source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“CRF is a 41 amino-acid residue peptide that plays a key role in orchestrating the endocrine, behavioral, and GI responses to stress (for review, see [327][328][329]).”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > CRF
What the sources say
- Not checked yetcites [327] Vale, 1981, Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin, Science source
- Not checked yetcites [328] Turnbull, 1997, Corticotropin-releasing factor (CRF) and endocrine responses to stress: CRF receptors, binding protein, and related peptides, Proc Soc Exp Biol Med source
- Not checked yetcites [329] Aubry, 2013, CRF system and mood disorders, J Chem Neuroanat source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In addition, chronically elevated plasma ghrelin, associated with changes in the gut microbiota, can prevent anxiety-and depression-like behavior through ghrelin receptors [309].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [309] Lutter, 2008, The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress, Nat Neurosci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“CRF 1 overexpression results in an anxiogenic-and depressive-like profile in rodents and humans [342][343][344][345][346].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [342] Kasahara, 2007, Altered behavioural adaptation in mice with neural corticotrophin-releasing factor overexpression, Genes Brain Behav source
- Not checked yetcites [343] Timpl, 1998, Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1, Nat Genet source
- Not checked yetcites [344] Fernández Macedo, 2013, Effects of fluoxetine on CRF and CRF1 expression in rats exposed to the learned helplessness paradigm, Psychopharmacology (Berl) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“acute stress in mice induced the release of intestinal CRF independently of the HPA axis [131].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [131] Sun, 2013, Stress-induced corticotropin-releasing hormone-mediated NLRP6 inflammasome inhibition and transmissible enteritis in mice, Gastroenterology source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Infants of mothers with high self-reported stress and high levels of salivary cortisol during pregnancy had a significantly higher relative abundance of Proteobacteria and lower relative abundances of lactic acid bacteria (i.e., Lactobacillus, Lactoccus, Aerococcus) and Bifidobacteria [358].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [358] Zijlmans, 2015, Maternal prenatal stress is associated with the infant intestinal microbiota, Psychoneuroendocrinology source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Lactobacillus also suppressed plasma corticosterone and hypothalamic CRFexpressing cells in rats that underwent water-avoidance stress [356].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [356] Takada, 2016, Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut–brain interaction in human and animal models, Neurogastroenterol Motil source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these data support a role for the gut microbiota as a potential treatment intervention to blunt stress reactivity.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Interestingly, administration of Clostridium butyricum from the phylum Firmicutes can block increased CRF levels in patients before surgical procedures [361].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [361] Yang, 2016, Probiotics reduce psychological stress in patients before laryngeal cancer surgery, Asia Pac J Clin Oncol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Recently, a study has found that a single administration of CRF modified the gut microbiota in rats, with specific reductions in Lactobacillus [349].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [349] Murakami, 2017, Changes in intestinal motility and gut microbiota composition in a rat stress model, Digestion source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, such data indicate that CRF-mediated activation of the HPA axis depends on the gut microbiota.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Increased CRF concentration in the cerebrospinal fluid was also reported in depressive patients and victims of suicide [359,360].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, antidepressant treatment normalizes expression of CRF and CRF 1 receptors in association with remission of depression [329,344,346].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [329] Aubry, 2013, CRF system and mood disorders, J Chem Neuroanat source
- Not checked yetcites [344] Fernández Macedo, 2013, Effects of fluoxetine on CRF and CRF1 expression in rats exposed to the learned helplessness paradigm, Psychopharmacology (Berl) source
- Not checked yetcites [346] Stout, 2002, Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment, J Pharmacol Exp Ther source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Using a mixture of 8 bacterial strains, including Lactobacillus and Bifidobacterium, Abildgaard et al. [357] observed lowered hippocampal transcript levels of CRF receptors followed by marked reduction in depressive-like behavior in rats.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [357] Abildgaard, 2017, Probiotic treatment reduces depressive-like behaviour in rats independently of diet, Psychoneuroendocrinology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These effects in the HPA axis are normalized in recolonized germ-free mice [216].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [216] Sudo, 2004, Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice, J Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, the administration of oxytocin exerts an antidepressant-like effect in rodents [374-377]”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Oxytocin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [374] Cohen, 2010, Hippocampal microinfusion of oxytocin attenuates the behavioural response to stress by means of dynamic interplay with the glucocorticoid-catecholamine responses, J Neuroendocrinol source
- Not checked yetcites [375] Landgraf, 2003, Born to be anxious: neuroendocrine and genetic correlates of trait anxiety in HAB rats, Stress source
- Not checked yetcites [376] Slattery, 2010, Chronic icv oxytocin attenuates the pathological high anxiety state of selectively bred Wistar rats, Neuropharmacology source
- Not checked yetcites [377] Norman, 2010, Social interaction prevents the development of depressive-like behavior post nerve injury in mice: a potential role for oxytocin, Psychosom Med source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, gut microbiota depletion from early adolescence impacts oxytocin signaling, reducing both hypothalamic oxytocin and vasopressin levels in mice subjected to stress [21,379].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Oxytocin: Relevance to Anxiety and Depression
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, the effects observed above are dependent on vagal signaling, which blunted the effects of Lactobacillus on host plasma and hypothalamic oxytocin [132,133].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Oxytocin: Relevance to Anxiety and Depression
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Allen et al. [52] found that healthy individuals fed Bifidobacterium longum had attenuated levels of cortisol and reduced subjective anxiety in response to the socially evaluated cold stress pressor test.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [52] Allen, 2016, Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers, Transl Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In a separate investigation, participants consumed a fermented milk product containing Lactobacillus casei selfreported the same as the control subjects [49].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [49] Benton, 2007, Impact of consuming a milk drink containing a probiotic on mood and cognition, Eur J Clin Nutr source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, the quality of the diet (i.e., a typical Western diet rich in fat and protein) drastically reduces Bifidobacteria and butyrate-producing bacteria [386, 387]”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [386] Brinkworth, 2009, Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo, Am J Clin Nutr source
- Not checked yetcites [387] Russell, 2011, High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health, Am J Clin Nutr source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, when only participants whose baseline mood scores were lower (indicative of an antidepressive state), probiotic supplementation resulted in significantly more of this group of participants selfscoring as happy rather than depressed compared with placebo [49].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [49] Benton, 2007, Impact of consuming a milk drink containing a probiotic on mood and cognition, Eur J Clin Nutr source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For example, changes in diet even for a short duration (24 h) can drastically alter the composition of the gut microbiota [385].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [385] David, 2014, Diet rapidly and reproducibly alters the human gut microbiome, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“whereas a Mediterranean diet, which is thought of as a healthy diet, shows significant increases in SCFAs [43].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [43] De Filippis, 2016, High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome, Gut source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, the probiotic Lactobacillus rhamnosus failed to alter mood, anxiety, and stress-related measures when subjects faced a socially evaluated cold pressor test [392]”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [392] Kelly, 2017, Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects, Brain Behav Immun source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As suggested here, peptides released by specialized cells in the gut participate in gut-to-brain communication.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Conclusion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“indicating that this probiotic may reduce limbic reactivity.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [167] Pinto-Sanchez, 2017, Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome, Gastroenterology source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Moreover, a recent paper described that commensal bacteria are able to produce G-protein-coupled receptor agonists to regulate the GI tract physiology, including metabolic hormones and glucose homeostasis [4].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Targeting Gut Peptides
What the sources say
- Not checked yetcites [4] Cohen, 2017, Commensal bacteria make GPCR ligands that mimic human signalling molecules, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In recent studies investigating patients with depression and anxiety, a mixture of the probiotics Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum found a significant decrease in depression scores [393]”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [393] Akkasheh, 2016, Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial, Nutrition source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nevertheless, the dynamic changes in peptides and respective receptor expression in the gut and brain of rodents and humans with altered microbiota attests to a profound role of the gut bacteria on peptides.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Conclusion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the diverse pathways by which the gut can signal the brain, the endocrine system seems to play an important role, as it is capable of modulating not only other endocrine functions, but also the neural and immune systems.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Schmidt et al. [391] found that Bimuno galactooligosaccharides intake decreased attentional vigilance to negative versus positive information.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [391] Schmidt, 2015, Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers, Psychopharmacology (Berl) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 22
- It may state two separate claims as one. 73
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Nevertheless, a direct link between the gut microbiota and the modulation of ghrelin remains absent.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Alterations in the gut microbiota may influence conditions such as obesity, allergies, autoimmune disorders, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and psychiatric disorders [8][9][10][11][12][13].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Introduction
What the sources say
- Not checked yetcites [8][9][10][11][12][13]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota.”
- Also stated in: § Introduction · plain
“Enteric bacterial diversity and composition uniquely influence the release of gut peptides, including glucagon-like peptide (GLP-1), peptide YY (PYY), cholecystokinin (CCK), corticotropin-releasing factor (CRF), oxytocin, and ghrelin [1,[5][6][7].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Abstract
What the sources say
- Not checked yetcites [1,[5][6][7]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Introduction · plain
In the paper
“The more than 20 signaling molecules released from specialized enteroendocrine cells (EECs) in the GI tract have significant endocrine and metabolic functions and are able to communicate with the brain [1].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Introduction
What the sources say
- Not checked yetcites [1] Dockray, 2014, Gastrointestinal hormones and the dialogue between gut and brain, J Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microbiotagut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
In the paper
“Following secretion, gut peptides diffuse throughout the lamina propria, which is occupied by a variety of immune cells, ultimately to reach the bloodstream, to stimulate sensory neurons and potentially to act on the vagus nerve, thereby creating an intersection for gut peptidergic signaling to the brain [111].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut peptide receptor
What the sources say
- Not checked yetcites [111] Okano-Matsumoto, 2011, Electrophysiological evidence for distinct vagal pathways mediating CCK-evoked motor effects in the proximal versus distal stomach, J Physiol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Owing to the wide expression of peptides and their receptors in both brain and gut, in addition to their facilitated transit into the bloodstream, it seems reasonable to assume that these peptides can act beyond their primary signaling function, suggesting a possible role (most likely indirect) of the gut peptides in neuropsychiatric disorders [5].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut peptide receptor
What the sources say
- Not checked yetcites [5] Latorre, 2016, Enteroendocrine cells: a review of their role in brain-gut communication, Neurogastroenterol Motil source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Owing to their privileged location in the GI tract, it is possible that those peptides may be influenced by changes in the gut microbiota and modulate (directly or indirectly) upstream signaling to the brain.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut peptide receptor
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“In a complementary manner, the blood-brain barrier (BBB) selectively facilitates the transport of some peptides in the blood-to-brain direction, suggesting a direct pathway for some gut peptides that are not quickly degraded after their release [112][113][114][115].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut peptide receptor
What the sources say
- Not checked yetcites [112][113][114][115]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The dynamic profile of gut peptides, including their direct link with mood disorders, and their broad role in the gut suggests that the microbiota-gut peptide-brain communication axis can be a target for psychobiotics to prevent and treat such disorders (Table 1).”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut peptide receptor
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Depression and anxiety are often accompanied by changes in colonic motility, which, in turn, alters the composition and stability of the gut microbiota, as well as the colonic physiology and morphology [137-140].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [137] Bailey, 1999, Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys, Dev Psychobiol source
- Not checked yetcites [138] Park, 2013, Altered colonic function and microbiota profile in a mouse model of chronic depression, Neurogastroenterol Motil source
- Not checked yetcites [139] Rodes, 2011, Transit time affects the community stability of LactobacillusBifidobacterium species in an in vitro model of human colonic microbiotia, Artif Cells Blood Substit Immobil Biotechnol source
- Not checked yetcites [140] O'Malley, 2010, Distinct alterations in colonic morphology and physiology in two rat models of enhanced stress-induced anxiety and depression-like behaviour, Stress source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“SCFA act on G-protein-coupled receptors [free fatty acid (FFA) receptors] located along the GI tract to regulate energy homeostasis via the stimulation of leptin production in adipocytes, and the secretion of gut peptides from colonic EECs [84][85][86][87].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota
What the sources say
- Not checked yetcites [84][85][86][87]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Since the expression of these gut-derived peptides is likely to be modulated by changes in the gut microbiota, it has been proposed that these peptide hormones may have an important role in gut-brain communication [21,[25][26][27].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Introduction
What the sources say
- Not checked yetcites [21,[25][26][27]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the altered gut microbiota and its effects on host metabolic phenotype during psychiatric illness remains unknown, these observations highlight the potential association of the gut microbiota with host depression and anxiety.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Likewise, in IBS, a disease linked to alterations in the immune system [144], a correlation was found between gut microbiota composition and brain volumes in patients with IBS with early life trauma, suggesting a shift in the Firmicutes/Bacteroidetes ratio, with Firmicutes increased and Bacteriodetes decreased [53].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [53] Labus, 2017, Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome, Microbiome source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Antidepressants are well known to have antimicrobial effects, modulating the pathophysiology of the anxiety and depression by reshaping not only brain biochemistry, but also the gut microbiota [159,160].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [159] Lieb, 2004, The immunostimulating and antimicrobial properties of lithium and antidepressants, J Infect source
- Not checked yetcites [160] Munoz-Bellido, 2000, Antimicrobial activity of psychotropic drugs. Selective serotonin reuptake inhibitors, Int J Antimicrob Agents source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“NPY is the most abundant peptide in the brain and is expressed from the medullary brainstem to the cerebral cortex (for review, see [175]).”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Neuropeptide Y Family
What the sources say
- Not checked yetcites [175] Kask, 2002, The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y, Neurosci Biobehav Rev source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both PYY and PP are able to cross the BBB by transmembrane diffusion and bind cognate receptors located in the area postrema [115,178].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Neuropeptide Y Family
What the sources say
- Not checked yetcites [115] Nonaka, 2003, Characterization of blood-brain barrier permeability to PYY3-36 in the mouse, J Pharmacol Exp Ther source
- Not checked yetcites [178] Dumont, 2007, Distribution of peripherally injected peptide YY ([125I] PYY (3-36)) and pancreatic polypeptide ([125I] hPP) in the CNS: enrichment in the area postrema, J Mol Neurosci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Stress-related disorders can also alter the intestinal barrier, triggering a Bleaky gut^, which could allow a microbiota-driven proinflammatory response through the translocation of certain bacterial products from the gut [141-143].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [141] Kelly, 2015, Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders, Front Cell Neurosci source
- Not checked yetcites [142] Maes, 2012, Increased IgA and IgM responses against gut commensals in chronic depression: Further evidence for increased bacterial translocation or leaky gut, J Affect Disord source
- Not checked yetcites [143] Maes, 2008, The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression, Neuro Endocrinol Lett
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Stressed mice also have been shown to have greater populations of the genus Clostridium, which agrees with the gut microbiota profile in maternally separated rodents [149-151].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [149] Bailey, 2011, Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation, Brain Behav Immun source
- Not checked yetcites [150] De Palma, 2015, Microbiota and host determinants of behavioural phenotype in maternally separated mice, Nat Commun source
- Not checked yetcites [151] O'Mahony, 2011, Strain differences in the neurochemical response to chronic restraint stress in the rat: relevance to depression, Pharmacol Biochem Behav source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Yu et al. [148] found that depressive-like rats had the relative Stomach Small intestine Colon abundances of Bacteroidetes significantly increased, whereas that of Firmicutes was markedly decreased.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > The Gut Microbiota in Anxiety and Depression
What the sources say
- Not checked yetcites [148] Yu, 2017, Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics, J. Pharm Biomed Anal source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although plasma PYY is increased after oligofructose treatment in healthy rats [202,203], oligofructose did not alter plasma PYY levels in obese mice [204].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [202] Hong, 2016, Evaluation of prebiotic effects of high-purity galactooligosaccharides in vitro and in vivo, Food Technol Biotechnol source
- Not checked yetcites [203] Cluny, 2015, Interactive effects of oligofructose and obesity predisposition on gut hormones and microbiota in diet-induced obese rats, Obesity source
- Not checked yetcites [204] Steensels, 2017, Supplementation of oligofructose, but not sucralose, decreases high-fat diet induced body weight gain in mice independent of gustducin-mediated gut hormone release, Mol Nutr Food Res source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“By activating Y 4 receptors in the gut, PP reduces intestinal motor activity and facilitates nutrient absorption, an effect likewise exerted by PYY [24,188,190].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [24] Holzer, 2012, Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis, Neuropeptides source
- Not checked yetcites [188] Fujimiya, 2000, Peptidergic regulation of gastrointestinal motility in rodents, Peptides source
- Not checked yetcites [190] Tough, 2006, Y(4) receptors mediate the inhibitory responses of pancreatic polypeptide in human and mouse colon mucosa, J Pharmacol Exp Ther source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the gut microbiota was not investigated in these studies, the results strongly suggest a potential role for gut-brain communication through Y 4 signaling.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, Schéle et al. [116] found that administration of leptin reduced NPY expression in germ-free mice but not in conventionally raised mice, suggesting that the gut microbiota may decrease leptin sensitivity, effects that are dependent on vagal signaling [192].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [116] Schéle, 2013, The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system, Endocrinology source
- Not checked yetcites [192] De Lartigue, 2010, EGR1 is a target for cooperative interactions between cholecystokinin and leptin, and inhibition by ghrelin, in vagal afferent neurons, Endocrinology source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, the SCFA butyrate can increase the expression of receptors that sense microbial compounds (Toll-like receptors), which, in turn, increases the expression of PYY [201].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [201] Larraufie, 2017, TLR ligands and butyrate increase Pyy expression through two distinct but inter-regulated pathways, Cell Microbiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given the importance of microbiota-generated SCFAs such as butyrate, the role of the SCFA in mediating PYY expression through immune cells could be an important link in microbial-host communication and PYY signaling.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite the interspecies variability, the contrasting results found in humans and animals could be owing to the selective spectrum of bacteria that can modulate PYY expression.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Recently, it was shown that the depletion of the gut microbiota in adult mice upregulated NPY expression within the amygdala and hypothalamus, followed by cognitive deficits [25], an effect also observed in rats housed in environmental enrichment [213].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [25] Fröhlich, 2016, Cognitive impairment by antibiotic-induced gut dysbiosis: analysis of gut microbiota-brain communication, Brain Behav Immun source
- Not checked yetcites [213] Lach, 2016, Short-term enriched environment exposure facilitates fear extinction in adult rats: the NPY-Y1 receptor modulation., Neuropeptides source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, circulating levels of plasma PYY and NPY are also enhanced in patients with IBD, suggesting that the epithelial levels of NPY and PYY are exhausted by excessive release of these peptides from EECs and intestinal neurons [173].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [173] El-Salhy, 2016, The role of the neuropeptide Y (NPY) family in the pathophysiology of inflammatory bowel disease (IBD), Neuropeptides source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In the brain, GLP-1 is present in the NTS and the olfactory bulb [5,224].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > GLP-1
What the sources say
- Not checked yetcites [5] Latorre, 2016, Enteroendocrine cells: a review of their role in brain-gut communication, Neurogastroenterol Motil source
- Not checked yetcites [224] Vrang, 2010, Preproglucagon derived peptides GLP-1, GLP-2 and oxyntomodulin in the CNS: role of peripherally secreted and centrally produced peptides, Prog Neurobiol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For this, Rajpal et al. [207] investigated selective spectrum antibiotics and found that only an alteration of Gramnegative bacteria (which, in turn, increased the population of Firmicutes) improved metabolic aspects, including PYY, in rodents.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [207] Rajpal, 2015, Selective spectrum antibiotic modulation of the gut microbiome in obesity and diabetes rodent models, PLOS ONE source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, in addition to the literature mentioned above, this indicates that NPY, PYY, and PP somehow participate in the reciprocal interaction between the brain, the gut, and the immune system, therefore warranting investigation of their pathophysiological implications within the context of the microbiota-gut-brain axis.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
In the paper
“GLP-1, an incretin hormone, is a 30 amino-acid peptide derived from t he post-translational processing of preproglucagon, which is involved in the neural regulation of food intake, body weight, the modulation of the hypothalamic-pituitary-adrenal (HPA) axis, and overall response to stress via activation of the GLP-1 receptor (for review, see [220][221][222][223]).”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > GLP-1
What the sources say
- Not checked yetcites [220][221][222][223]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Finally, NPY and PYY are also antimicrobial peptides, influencing the composition and function of the gut microbiota [219].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Microbiota and the NPY, PYY, and PP: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [219] El Karim, 2008, Antimicrobial activity of neuropeptides against a range of micro-organisms from skin, oral, respiratory and gastrointestinal tract sites, J Neuroimmunol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As the NTS projects GLP-1 neurons directly to the paraventricular nucleus of the hypothalamus, it is plausible to affirm that GLP-1 restricts feeding behavior, which is dependent of the vagal pathway [230][231][232].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > GLP-1
What the sources say
- Not checked yetcites [230][231][232]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, anxiety-like behavior in diabetic mice was blunted by a GLP-1 receptor agonist [247, 248], whereas in nondiabetic animals, the impact of a GLP-1 receptor agonist was less clear in reducing anxiety-like behavior [249-251].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [247] Komsuoglu Celikyurt, 2014, Exenatide treatment exerts anxiolytic- and antidepressant-like effects and reverses neuropathy in a mouse model of type-2 diabetes, Med Sci Monit Basic Res source
- Not checked yetcites [248] Sharma, 2015, Glucagon-like peptide-1 (GLP-1) receptor agonist prevents development of tolerance to anti-anxiety effect of ethanol and withdrawal-induced anxiety in rats, Metab Brain Dis source
- Not checked yetcites [249] Kinzig, 2003, CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors, J Neurosci source
- Not checked yetcites [250] Krass, 2015, GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment, Acta Neuropsychiatr source
- Not checked yetcites [251] Möller, 2002, Anxiogenic-like action of centrally administered glucagon-like peptide-1 in a punished drinking test, Prog Neuropsychopharmacol Biol Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, vagal afferent neurons express the GLP-1 receptor, activation of which induces firing of the respective vagal afferent neurons and most likely stimulation of NTS [228,229].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > GLP-1
What the sources say
- Not checked yetcites [228] Kakei, 2002, Glucagon-like peptide-1 evokes action potentials and increases cytosolic Ca2+ in rat nodose ganglion neurons, Auton Neurosci source
- Not checked yetcites [229] Katsurada, 2014, Endogenous GLP-1 acts on paraventricular nucleus to suppress feeding: projection from nucleus tractus solitarius and activation of corticotropin-releasing hormone, nesfatin-1 and oxytocin neurons, Biochem Biophys Res Commun source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the NTS, GLP-1 fibers directly innervate hypophysiotrophic CRF neurons in the paraventricular nucleus (PVN), where GLP-1 activates the HPA axis response [225].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > GLP-1
What the sources say
- Not checked yetcites [225] Rinaman, 1999, Interoceptive stress activates glucagon-like peptide-1 neurons that project to the hypothalamus, Am J Physiol
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“GLP-1 levels in the lymph were found to be higher, lasting longer than in the bloodstream, supporting a plausible model where GLP-1 does reach the brain given its transport via the lymph [233].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > GLP-1
What the sources say
- Not checked yetcites [233] D'Alessio, 2007, Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph system, Am J Physiol Regul Integr Comp Physiol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The densities of CCK cells are reduced in IBD, which may lower the levels of gastric secretion, such as bicarbonate, pancreatic enzymes, and bile salts, resulting in the development of IBS [283,284].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [283] Hsu, 2016, Gut-derived cholecystokinin contributes to visceral hypersensitivity via nerve growth factor-dependent neurite outgrowth, J Gastroenterol Hepatol source
- Not checked yetcites [284] El-Salhy, 2015, Reduction in duodenal endocrine cells in irritable bowel syndrome is associated with stem cell abnormalities, World J Gastroenterol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As CCK has been reported to have anti-inflammatory effects, reduced expression of CCK in the gut may have an impact on gut inflammatory diseases, with subsequent consequences in IBD or IBS comorbidity.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, systemic administration of CCK-8 elevated the levels of brain-derived neurotrophic factor in the rat hippocampus, suggesting a neuroplasticity-related effect mediated by CCK [276].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [276] Tirassa, 2007, CCK-8 induces NGF and BDNF synthesis and modulates TrkA and TrkB expression in the rat hippocampus and septum: effects on kindling development, Neurochem Int source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, vagotomy in mice attenuates the effects of CCK on gastric emptying, whereas the administration of LPS abolishes CCK-induced inhibition of food intake [281,282].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [281] de La Serre, 2015, Chronic exposure to low dose bacterial lipopolysaccharide inhibits leptin signaling in vagal afferent neurons, Physiol Behav source
- Not checked yetcites [282] Bauer, 2016, Regulation of energy balance by a gut–brain axis and involvement of the gut microbiota, Cell Mol Life Sci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, a GLP-1 receptor agonist was able to reverse LPS-induced depressive-like behavior without directly affecting inflammatory cytokines [256].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [256] Ventorp, 2017, Exendin-4 treatment improves LPS-induced depressive-like behavior without affecting pro-inflammatory cytokines, J Parkinsons Dis source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In patients with mood disorders and the presence of cognitive deficits, it was found that 4-week treatment with a GLP-1 agonist reverted the cognitive deficits without affecting metabolic parameters, suggesting GLP-1 target offers beneficial effects in some symptoms that can be overrepresented in psychiatric disorders [267].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [267] Mansur, 2017, Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: a pilot, open-label study, J Affect Disord source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, chronic systemic stimulation of GLP-1 receptors promoted antidepressant-like effects in rodents, coupled with increasing hippocampal neurogenesis, suggesting plasticity-related effects could underpin such effects [252][253][254][255].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [252][253][254][255]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, the localization of GLP-1 and the GLP-1 receptors in the gut-brain axis underscores the importance of the microbiota in the modulatory role for GLP-1 in the central regulation of energy homeostasis, which may influence depression and anxiety associated with metabolic dysfunctions.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and GLP-1: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CCK is the first peptide released postprandially to reduce food intake in both obese and lean individuals, remaining in the bloodstream for about 3 h [277, 278].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [277] Mishra, 2016, Obesity: an overview of possible role(s) of gut hormones, lipid sensing and gut microbiota, Metabolism source
- Not checked yetcites [278] Rehfeld, 2001, The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33, J Clin Endocrinol Metab
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor type 1a and was first discovered for its stimulation of growth hormone secretion from the pituitary [293].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Ghrelin
What the sources say
- Not checked yetcites [293] Kojima, 1999, Ghrelin is a growth-hormone-releasing acylated peptide from stomach, Nature source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Ghrelin crosses the BBB via active transport and direct diffusion, making the ghrelinergic system ideally placed to play an important role in the stress response [112,297,302].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [112] Banks, 2002, Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure, J Pharmacol Exp Ther source
- Not checked yetcites [297] Schellekens, 2012, Ghrelin signalling and obesity: at the interface of stress, mood and food reward, Pharmacol Ther source
- Not checked yetcites [302] Schaeffer, 2013, Rapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons, Proc Natl Acad Sci U S A source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The importance of the microbiota in the modulatory role for CCK in the central regulation of energy homeostasis may influence depression and anxiety associated with obesity and represent a potential target in this specific aspect of emotionality.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CCK: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“antagonists of GHS receptor administered during repeated stressors prevented fear memory formation, as well as anxiety and depression-like phenotypes in mice [296,315].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [296] Huang, 2017, Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents, Behav Brain Res source
- Not checked yetcites [315] Meyer, 2014, A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear, Mol Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nevertheless, it appears that in addition to its effects on feeding, ghrelin enhances the release of NPY onto GABAergic nerve terminals adjacent to CRH neurons, disinhibiting these neurons and stimulating CRF release into the pituitary-hypophyseal portal circulation, driving increased ACTH secretion from the pituitary [28,308].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Ghrelin
What the sources say
- Not checked yetcites [28] Cowley, 2003, The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis, Neuron source
- Not checked yetcites [308] Arvat, 2001, Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone, J Clin Endocrinol Metab
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, mice lacking growth hormone secretagogue (GHS) receptors are more susceptible to stress and exhibit anxiety-and depressive-like behavior [309,312].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [309] Lutter, 2008, The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress, Nat Neurosci source
- Not checked yetcites [312] Walker, 2015, The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis, Mol Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“However, after a period of fasting, germ-free mice have higher plasma ghrelin concentrations than conventionally colonized mice, which could reflect a direct effect of fasting and not the microbiota profile on ghrelin release [121].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [121] Khosravi, 2015, Helicobacter pylori infection can affect energy modulating hormones and body weight in germ free mice, Sci Rep source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The use of dietary capsaicin was shown to increase the Firmicutes/Bacteroidetes ratio, which was associated with decreased plasma ghrelin levels and an increase in butyrate [325].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [325] Kang, 2016, Healthy subjects differentially respond to dietary capsaicin correlating with specific gut enterotypes, J Clin Endocrinol Metab source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Ghrelin has also been shown to decrease in response to the prebiotic supplementation inulin and oligofructose uniquely in obese and lean rodents, with obese rats showing attenuated ghrelin levels [117, 122, 127].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [117] Parnell, 2012, Prebiotic fibres dose-dependently increase satiety hormones and alter Bacteroidetes and Firmicutes in lean and obese JCR:LA-cp rats, Br J Nutr source
- Not checked yetcites [122] Cani, 2004, Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats, Br J Nutr source
- Not checked yetcites [127] Cani, 2005, Oligofructose promotes satiety in rats fed a high-fat diet: involvement of glucagon-like peptide-1, Obes Res source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Then, ACTH passes into systemic circulation to cause the release of cortisol (in humans) or corticosterone (in rodents) from the adrenal glands [328,330].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > CRF
What the sources say
- Not checked yetcites [328] Turnbull, 1997, Corticotropin-releasing factor (CRF) and endocrine responses to stress: CRF receptors, binding protein, and related peptides, Proc Soc Exp Biol Med source
- Not checked yetcites [330] Tsatsanis, 2007, The corticotropin-releasing factor (CRF) family of peptides as local modulators of adrenal function, Cell Mol Life Sci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since the gut microbiota strongly affects the immune system, intestinal diseases where the gut microbiota is changed, such as IBS and IBD, may induce the expression of inflammatory cells, which, in turn, can increase expression of glucocorticoids but not CRF.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > CRF
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The gut microbiota strongly affects the immune system.
None of the sources cited for this claim have been checked yet.
In the paper
“In humans, the relationship between the gut microbiota and ghrelin levels seems to mirror that in rodents where the relative abundance of bacterial taxa such as Bacteroides was negatively correlated with plasma ghrelin, which, in obese patients, was increased [130,197,292].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [130] Glintborg, 2006, Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls, Eur J Endocrinol source
- Not checked yetcites [197] Liu, 2017, Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome, Front Microbiol
- Not checked yetcites [292] Federico, 2016, Gastrointestinal hormones, intestinal microbiota and metabolic homeostasis in obese patients: effect of bariatric surgery, In Vivo
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Interestingly, plasma ghrelin did not return to levels found in normal weight individuals after obese patients underwent bariatric surgery, despite a postoperative increase of Lactobacillus and Streptococcus [292].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [292] Federico, 2016, Gastrointestinal hormones, intestinal microbiota and metabolic homeostasis in obese patients: effect of bariatric surgery, In Vivo
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, the SCFA butyrate, as well as physical exercise, reduce serum ghrelin levels through involvement of FFA3 receptor [105, 318].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Ghrelin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [105] Lin, 2012, Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms, PLOS ONE
- Not checked yetcites [318] Queipo-Ortuño, 2013, Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels, PLOS ONE source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CRFbinding protein is thought to play an inhibitory role in which it binds CRF to prevent the activation of CRF receptors [336].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > CRF
What the sources say
- Not checked yetcites [336] Seasholtz, 2002, Corticotropin-releasing hormone-binding protein: Biochemistry and function from fishes to mammals, J Endocrinol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Interestingly, the depletion of the gut microbiota via antibiotic treatment in mice from weaning onward does not alter hypothalamic mRNA CRF expression in adulthood, even when mice underwent acute restraint stress [21], suggesting gut microbiota-mediated CRF signaling may occur during early life.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [21] Desbonnet, 2015, Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour, Brain Behav Immun source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Sun et al. [131] also observed changes in gut microbiota composition, which was reverted with a probiotic supplement.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [131] Sun, 2013, Stress-induced corticotropin-releasing hormone-mediated NLRP6 inflammasome inhibition and transmissible enteritis in mice, Gastroenterology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Whereas the absence of CRF 1 receptors impairs basal and stress-induced HPA axis response and induces an anxiolytic-and antidepressant-like effect [329, 340, 341]”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [329] Aubry, 2013, CRF system and mood disorders, J Chem Neuroanat source
- Not checked yetcites [340] Habib, 2000, Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates, Proc Natl Acad Sci U S A source
- Not checked yetcites [341] Smith, 1998, Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development, Neuron source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Prenatal stress induced depressive-like behavior in adulthood mice, which led to a long-lasting change of the enteric microbiota composition associated with an exaggerated HPA axis response to stress [353][354][355].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [353] Jašarević, 2015, Alterations in the vaginal microbiome by maternal stress are associated with metabolic reprogramming of the offspring gut and brain, Endocrinology source
- Not checked yetcites [354] Golubeva, 2015, Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood, Psychoneuroendocrinology source
- Not checked yetcites [355] Abe, 2007, Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis, Neurosci Res source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Germ-free rodents have increased hypothalamic CRF gene expression, as well as circulating levels of ACTH and corticosterone to acute restraint stress in adulthood [27,216].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [27] Crumeyrolle-Arias, 2014, Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats, Psychoneuroendocrinology source
- Not checked yetcites [216] Sudo, 2004, Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice, J Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The central administration of CRF in rodents induces depressive and anxiolytic-like behavior, which was followed by changes in the intestinal microbial community [138].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [138] Park, 2013, Altered colonic function and microbiota profile in a mouse model of chronic depression, Neurogastroenterol Motil source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Early-life stress such as maternal separation results in changes in the gut microbiota followed by an increase in stress reactivity, including a decrease in Lactobacillus in adult mice [137].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [137] Bailey, 1999, Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys, Dev Psychobiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In yet another study, healthy participants who ingested Lactobacillus helveticus and Bifidobacterium longum showed less self-reported negative mood and decreased urinary cortisol [50,390].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Towards a New Class of Psychiatric Treatments
What the sources say
- Not checked yetcites [50] Messaoudi, 2011, Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers, Gut Microbes source
- Not checked yetcites [390] Messaoudi, 2010, Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects, Br J Nutr source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Oleoylethanolamide, a product of fat absorption, which has antidepressant-like and neuroimmune properties [380,381], excites vagal afferent neurons and stimulates both axonal and somatodendritic oxytocin secretion [382][383][384].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Oxytocin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [382] Gaetani, 2010, The fat-induced satiety factor oleoylethanolamide suppresses feeding through central release of oxytocin, J Neurosci source
- Not checked yetcites [383] Romano, 2013, The satiety signal oleoylethanolamide stimulates oxytocin neurosecretion from rat hypothalamic neurons, Peptides source
- Not checked yetcites [384] Wang, 2005, Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1, J Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These patients also presented a reduced degree of anxiety before surgery, suggesting an interesting effect of probiotics in mediating CRF expression to modulate stress reactivity.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and CRF: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [361] Yang, 2016, Probiotics reduce psychological stress in patients before laryngeal cancer surgery, Asia Pac J Clin Oncol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nonetheless, plasticity in the oxytocin system is likely a protective coping mechanism in response to stress shaped by the gut microbiota during the early life stage, mainly through maternal exchange, which can contribute to depressive phenotypes when offspring become adults.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Oxytocin: Relevance to Anxiety and Depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although oxytocin facilitates parturition and lactation in females, decreased oxytocin levels have been linked with depression (not only postpartum depression) and maternal neglect [362,363].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Oxytocin
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“There is little evidence that oxytocin is modulated by gut bacteria, although gut microbiota seems to influence oxytocin in the brain [21,26].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Oxytocin
What the sources say
- Not checked yetcites [21] Desbonnet, 2015, Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour, Brain Behav Immun source
- Not checked yetcites [26] Buffington, 2016, Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring, Cell source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“whereas lowered oxytocin levels observed in nonweaned rats induces a depressive-like phenotype, which correlates positively with changes in the gut bacterial taxa [378].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Oxytocin: Relevance to Anxiety and Depression
What the sources say
- Not checked yetcites [378] Farshim, 2016, Maternal weaning modulates emotional behavior and regulates the gut-brain axis, Sci Rep source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, microbiota-derived metabolites might be able directly to modify gut-peptide receptors, displaying gut-peptide mimicry.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“antimicrobials such as bacteriocins may help gain terrain over neighbor competitors.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Targeting Gut Peptides
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: The nature of bacteria that occupy overlapping niches is to compete for the same nutrients.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The generation of specialized psychobiotics to modify gut hormone secretion from EECs may represent feasible and therapeutic microbiota-based strategies for the treatment of depression and anxiety disorders.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is significant anatomical and functional overlap of peptides released in the gut and brain, suggesting that these peptides exert common downstream effects on neural systems involved in mental health.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Conclusion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, the manipulation of gut peptides via psychobiotics may represent a promising opportunity to target mental disorders from the site of the GI tract.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Targeting Gut Peptides
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“There are major challenges associated with the development of peptide therapeutics, including limited peptide stability, a short duration of action, and the ability to cross the BBB [394,395].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Targeting Gut Peptides
What the sources say
- Not checked yetcites [394] Rafferty, 2016, Peptide therapeutics and the pharmaceutical industry: barriers encountered translating from the laboratory to patients, Curr Med Chem source
- Not checked yetcites [395] Yin, 2017, Protein based therapeutic delivery agents: contemporary developments and challenges, Biomaterials source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, there is already strong evidence to support the influence of the enteric microbiome on brain function in health and disease, suggesting the gut microbiome plays a crucial role in normal brain development, as well as modulation of host physiological systems important in stress-related disorders.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Conclusion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since stress can alter the gut microbiota composition, it is not surprising that there is interaction between oxytocin and the gut microbiome.”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Gut Microbiota and Oxytocin: Relevance to Anxiety and Depression
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Stress can alter the gut microbiota composition.
None of the sources cited for this claim have been checked yet.
In the paper
“Bacteriocins are ribosomally synthesized peptides that are produced by bacteria to eliminate neighboring cells through toxic and immune functions, while protecting itself and its progeny [399-402].”
§ Anxiety, Depression, and the Microbiome: A Role for Gut Peptides > Psychobiotics: Targeting Gut Peptides
What the sources say
- Not checked yetcites [399] Walsh, 2015, In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project's reference genome database, BMC Microbiol source
- Not checked yetcites [400] Zheng, 2015, Thinking outside the brain for cognitive improvement: Is peripheral immunomodulation on the way?, Neuropharmacology source
- Not checked yetcites [401] Kommineni, 2015, Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract, Nature source
- Not checked yetcites [402] Corr, 2007, Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118, Proc Natl Acad Sci U S A source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Some patients are resistant to the therapeutic effects of conventional pharmacological therapies.
“Conversely, some patients are resistant to the therapeutic effects of conventional pharmacological therapies.”
The paper relies on this without support.
Alterations in gut microbiota cause changes in gut peptide release that are sufficient to affect brain function and behavior.
“Evidence of direct involvement interaction between the NPY system and the gut microbiota modulating behavior is lacking.”
The paper relies on this without support.
The gut microbiota strongly affects the immune system.
“Since the gut microbiota strongly affects the immune system”
The paper relies on this without support.
Stress can alter the gut microbiota composition.
“Since stress can alter the gut microbiota composition”
The paper relies on this without support.
The nature of bacteria that occupy overlapping niches is to compete for the same nutrients.
“Since the nature of bacteria that occupy overlapping niches is to compete for the same nutrients”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Disturbances in the composition of the microbiome have been linked to anxiety (Lach et al., 2018;Leclercq et al., 2016) and treatments aimed at normalising these disturbances using specific probiotics have been proposed (Yang, Wei, Ju, & Chen, 2019).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Lach et al., 2018
Citations
Cites
A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
Ghrelin is a growth-hormone-releasing acylated peptide from stomach
Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., & Kangawa, K. (1999) · Nature · doi:10.1038/45230 · Cited by 8,479
Human gut microbiome viewed across age and geography
Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Dominguez-Bello, M. G., Contreras, M., Magris, M., Hidalgo, G., Baldassano, R. N., Anokhin, A. P., et al. (2012) · Nature · doi:10.1038/nature11053 · Cited by 7,815
The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell Homeostasis
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413
Dominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774
Host-gut microbiota metabolic interactions
Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012) · Science · doi:10.1126/science.1223813 · Cited by 4,760
Vale, W., Spiess, J., Rivier, C., & Rivier, J. (1981) · Science · doi:10.1126/science.6267699 · Cited by 3,965
The Prevalence of Comorbid Depression in Adults With Diabetes
Anderson, R. J., Freedland, K. E., Clouse, R. E., & Lustman, P. J. (2001) · Diabetes Care · doi:10.2337/diacare.24.6.1069 · Cited by 3,926
Cited by
Sorted by citations
The gut microbiome as a modulator of healthy ageing
Ghosh, T. S., Shanahan, F., & O’Toole, P. W. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00605-x · Cited by 817
A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders
Sorboni, S. G., Moghaddam, H. S., Esfehani, R. J., & Soleimanpour, S. (2022) · Clinical Microbiology Reviews · doi:10.1128/cmr.00338-20 · Cited by 586
The Microbiota–Gut–Brain Axis in Psychiatric Disorders
Góralczyk-Bińkowska, A., Szmajda‐Krygier, D., & Kozłowska, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911245 · Cited by 569
Antibiotics, gut microbiota, and Alzheimer’s disease
Angelucci, F., Cechova, K., Amlerova, J., & Hort, J. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1494-4 · Cited by 454
Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health
Berding, K., Vlckova, K., Marx, W., Schellekens, H., Stanton, C., Clarke, G., Jacka, F., Dinan, T. G., & Cryan, J. F. (2021) · Advances in Nutrition · doi:10.1093/advances/nmaa181 · Cited by 451
Self-citation
Metadata
- Authors
- Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Cryan, John F.
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 15
- Issue
- 1
- Pages
- 36-59
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC5794698
- OpenAlex
- W2769787189
- Semantic Scholar
- be5e28f3ea23394eef9edebbb176acf8dd5b68ff
- Cited by
- 573
- References
- 421
- Citations by year
- 2026: 34 · 2025: 59 · 2024: 74 · 2023: 97 · 2022: 82 · 2021: 91 · 2020: 76 · 2019: 38 · 2018: 19
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science Foundation Ireland (SFI/12/RC/, 12/RC/2273, 12/RC/, SFI/12/RC/2273.)
- APC Microbiome Institute (SFI/12/RC/2273)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- gut microbiota, gut-brain axis, anxiety, depression, gut peptides, gastrointestinal hormones, neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, ghrelin, vagus nerve, stress-related psychiatric disorders
- MeSH terms
- Gastrointestinal Microbiome, Anxiety, Brain, Cholecystokinin, Corticotropin-Releasing Hormone, Depression, Endocrine System, Humans, Neuropeptide Y, Oxytocin, Peptide Hormones, Glucagon-Like Peptide 1, Ghrelin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
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