The DOI matches its Crossref record; 87 of the 87 references it cites were found in a registry or an index; none of the 105 sources its claims cite is checked for support yet.
Principles and clinical implications of the brain-gut-enteric microbiota axis
Open accessAbstract
While bidirectional brain–gut interactions are well known mechanisms for the regulation of gut function in both healthy and diseased states, a role of the enteric flora—including both commensal and pathogenic organisms—in these interactions has only been recognized in the past few years. The brain can influence commensal organisms (enteric microbiota) indirectly, via changes in gastrointestinal motility and secretion, and intestinal permeability, or directly, via signaling molecules released into the gut lumen from cells in the lamina propria (enterochromaffin cells, neurons, immune cells). Communication from enteric microbiota to the host can occur via multiple mechanisms, including epithelial-cell, receptor-mediated signaling and, when intestinal permeability is increased, through direct stimulation of host cells in the lamina propria. Enterochromaffin cells are important bidirectional transducers that regulate communication between the gut lumen and the nervous system. Vagal, afferent innervation of enterochromaffin cells provides a direct pathway for enterochromaffin-cell signaling to neuronal circuits, which may have an important role in pain and immune-response modulation, control of background emotions and other homeostatic functions. Disruption of the bidirectional interactions between the enteric microbiota and the nervous system may be involved in the pathophysiology of acute and chronic gastrointestinal disease states, including functional and inflammatory bowel disorders.
Overview
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Written from the paper’s full text.
TL;DR
This review synthesizes evidence for bidirectional signaling between the CNS and the enteric microbiota—the "brain–gut–enteric microbiota axis"—and proposes enterochromaffin cells as key bidirectional transducers. It argues that disruption of these interactions may contribute to functional and inflammatory bowel disorders, though causative roles remain unproven.
Key findings
- The brain can influence commensal organisms indirectly (via ANS-mediated changes in motility, secretion, and intestinal permeability) and directly via signaling molecules (catecholamines, serotonin, dynorphin, cytokines) released into the gut lumen from neurons, immune cells, and enterochromaffin cells.
- Microbe-to-host signaling occurs via epithelial receptor-mediated mechanisms (e.g., Toll-like receptors) and, when permeability is increased, through direct stimulation of lamina propria cells; the autoinducer-3–QseC system in enterohemorrhagic *E. coli* is activated by host norepinephrine, enabling interkingdom signaling during stress.
- Enterochromaffin cells are positioned to act as bidirectional transducers: they secrete serotonin and peptides in response to luminal microbial factors and central stimuli, and vagal afferents expressing 5-HT3R lie in close proximity.
- Germ-free mice showed less intense inflammation-associated hyperalgesia than conventional mice, associated with increased interleukin-10 expression, reversed by anti-interleukin-10 antibody; the human gut harbors 400–1,000 bacterial species with ~10¹¹ bacterial cells per gram of colon contents.
- Two cited RCTs: 4-week *Bifidobacterium lactis* reduced abdominal distention and accelerated orocecal/colonic transit in IBS with constipation; 8-week *Bifidobacterium infantis* improved symptoms and normalized the plasma IL-10:IL-12 ratio.
Methods
- Narrative review (not a primary study) summarizing preclinical and clinical evidence on bidirectional nervous system–enteric microbiota interactions.
- Draws on animal models (rhesus monkeys, mice, rats, pigs), in vitro studies, and human clinical trials, including cited randomized controlled trials of probiotics in IBS.
- Organizes evidence into brain-to-microbiota signaling, microbe-to-gut-to-brain signaling, enterochromaffin cell transduction, vagal transmission, homeostatic functions, and clinical/therapeutic implications.
Limitations
- The paper states that evidence is "often sparse," that host-to-enteric bacteria signaling has been characterized in detail only for pathogenic organisms and only for some molecules (norepinephrine, dynorphins, cytokines), and that considerably more data are needed to establish a causative role for microbiota changes in IBS symptoms.
- The paper notes most studies of CNS influence on microbiota used luminal bacterial populations from stool samples, with biofilm-adjacent organisms less well documented.
- Evident from the text: this is a review without primary data or systematic search methodology, and several proposed mechanisms (e.g., enterochromaffin cell signaling to brain function, adrenergic receptors on epithelial brush border) are explicitly described as not yet studied in detail.
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Claims the paper makes
72 Not checked yet · 40 Own interpretation · 1 No basis given
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In the paper
“the mechanisms that underlie the observed effects are poorly understood.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Introduction
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In the paper
“The enteric microbiota can directly influence gut homeostasis by the regulation of bowel motility and modulation of intestinal pain, immune responses, and nutrient processing.8-10”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Introduction
What the sources say
- Not checked yetcites [8] Husebye, E., Hellstrom, P. M., Sundler, F., Chen, J. & Midtvedt, T. Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G368–G380 (2001). source
- Not checked yetcites [9] Rhee, S. H. et al. Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation. Proc. Natl Acad. Sci. USA 102, 13610–13615 (2005). source
- Not checked yetcites [10] Ait-Belgnaoui, A. et al. Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction. Gut 55, 1090–1094 (2006). source
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In the paper
“Enterochromaffin cells are important bidirectional transducers that regulate communication between the gut lumen and the nervous system.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Abstract
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In the paper
“while accelerated intestinal transit, with an increased number of giant, migrating contractions, is seen in many diarrheal states, including diarrhea-predominant IBS.22”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS-related changes in gut environment
What the sources say
- Not checked yetcites [22] Chey, W. Y. et al. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am. J. Gastroenterol. 96, 1499–1506 (2001). source
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In the paper
“Impaired intestinal transit caused by compromised, migrating motor complexes (a motor pattern characteristic of the fasting state of the gastrointestinal tract that is under parasympathetic control), is associated with bacterial overgrowth in the small intestine.20”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS-related changes in gut environment
What the sources say
- Not checked yetcites [20] Van Felius, I. D. et al. Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis. Neurogastroenterol. Motil. 15, 267–276 (2003). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Different types of psychological stressors modulate the composition and total biomass of the enteric microbiota in both adult15 and newborn animals.16”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Brain to enteric microbiota signaling
What the sources say
- Not checked yetcites [15] Schaedler, R. W. & Dubos, R. J. The fecal flora of various strains of mice. Its bearing on their susceptibility to endotoxin. J. Exp. Med. 115, 1149–1160 (1962). source
- Not checked yetcites [16] Bailey, M. T. & Coe, C. L. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev. Psychobiol. 35, 146–155 (1999). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In this case, the shedding of lactobacilli may have been related to the stress-induced acceleration of intestinal transit, since normal bacterial levels were restored 1 week after separation.16”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Brain to enteric microbiota signaling
What the sources say
- Not checked yetcites [16] Bailey, M. T. & Coe, C. L. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev. Psychobiol. 35, 146–155 (1999). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Although different types of psychological stressors, including early-life stress and sustained stress, have been recognized as risk factors or promoters of events that result in disease exacerbation in patients with ulcerative colitis2 and IBS,3”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Introduction
What the sources say
- Not checked yetcites [2] Levenstein, S. et al. Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am. J. Gastroenterol. 95, 1213–1220 (2000). source
- Not checked yetcites [3] Whitehead, W. E., Crowell, M. D., Robinson, J. C., Heller, B. R. & Schuster, M. M. Effects of stressful life events on bowel symptoms: subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. Gut 33, 825–830 (1992). source
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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
“The activation of any of these systems, either alone or in combination, might influence enteric microbiota both indirectly, via changes in their environment, and directly, via host–enteric microbiota signaling.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Brain to enteric microbiota signaling
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In the paper
“Both sympathetic and parasympathetic nervous systems, which are part of the ANS, have a prominent role in the modulation of gut functions, such as motility, secretion of acid, bicarbonates and mucus, intestinal-fluid handling and mucosal immune response (reviewed elsewhere1).”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS-related changes in gut environment
What the sources say
- Not checked yetcites [1] Mayer, E. A. The neurobiology of stress and gastrointestinal disease. Gut 47, 861–869 (2000). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 31
- Probably not a substantial claim. 13
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 brain can influence commensal organisms (enteric microbiota) indirectly, via changes in gastrointestinal motility and secretion, and intestinal permeability, or directly, via signaling molecules released into the gut lumen from cells in the lamina propria (enterochromaffin cells, neurons, immune cells).”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Abstract
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
“In maternal separation-induced, postnatal stress, reduction in lactobacilli was associated with the appearance of stress-indicative behaviors, and affected animals were more susceptible than unstressed controls to opportunistic infection.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Brain to enteric microbiota signaling
What the sources say
- Not checked yetcites [16] Bailey, M. T. & Coe, C. L. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev. Psychobiol. 35, 146–155 (1999). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Vagal, afferent innervation of enterochromaffin cells provides a direct pathway for enterochromaffin-cell signaling to neuronal circuits, which may have an important role in pain and immune-response modulation, control of background emotions and other homeostatic functions.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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 role of the enteric microbiota in bidirectional gut–brain interactions in health and disease has received little attention until the past 5 years or so.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Introduction
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Both pre natal17 and postnatal stress16 were associated with transient reductions in the levels of the enteric microbiota in rhesus monkeys.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Brain to enteric microbiota signaling
What the sources say
- Not checked yetcites [17] Bailey, M. T. et al. Prenatal stress alters bacterial colonization of the gut in infant monkeys. J. Pediatr. Gastroenterol. Nutr. 38, 414–421 (2004). source
- Not checked yetcites [16] Bailey, M. T. & Coe, C. L. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev. Psychobiol. 35, 146–155 (1999). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In general, bacteria located in the biofilm seem to be less affected by environmental alterations, such as changes in intestinal transit rate and luminal contents, than luminal populations are, but seem to have increased involvement in bidirectional signaling with the host.19”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Brain to enteric microbiota signaling
What the sources say
- Not checked yetcites [19] Macfarlane, S. & Dillon, J. F. Microbial biofilms in the human gastrointestinal tract. J. Appl. Microbiol. 102, 1187–1196 (2007). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, several studies have demonstrated that stressful stimuli can enhance the permeability of the intestinal epithelium, which allows bacterial antigens to penetrate the gut epithelium and triggers an immune response in the intestinal mucosa.23-27”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS-related changes in gut environment
What the sources say
- Not checked yetcites [23] Kiliaan, A. J. et al. Stress stimulates transepithelial macromolecular uptake in rat jejunum. Am. J. Physiol. 275, G1037–G1044 (1998).
- Not checked yetcites [24] Groot, J. et al. Stress-induced decrease of the intestinal barrier function. The role of muscarinic receptor activation. Ann. NY Acad. Sci. 915, 237–246 (2000). source
- Not checked yetcites [25] Yates, D. A., Santos, J., Soderholm, J. D. & Perdue, M. H. Adaptation of stress-induced mucosal pathophysiology in rat colon involves opioid pathways. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G124–G128 (2001). source
- Not checked yetcites [26] Soderholm, J. D. et al. Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress. Am. J. Physiol. Gastrointest. Liver Physiol. 283, G1257–G1263 (2002). source
- Not checked yetcites [27] Jacob, C. et al. Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins. J. Biol. Chem. 280, 31936–31948 (2005). source
boosteddirect- 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
“The ANS also affects epithelial mechanisms involved in immune activation of the gut, either directly, through modulation of the response of the gut immune cells (for example, macrophages and mast cells) to luminal bacteria, or indirectly, through alteration of the access of luminal bacteria to gut immunocytes (Figure 2).”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS-related changes in gut environment
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In the paper
“Notably, most of the studies that have examined the influence of these systems on enteric microbiota have been performed on luminal bacterial populations from stool samples, whereas the influence of these systems on organisms contained in the biofilm adjacent to the intestinal mucosa are less well documented.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Brain to enteric microbiota signaling
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In the paper
“For example, serotonin secretion into the stomach lumen has been reported in response to an intrathecal injection into the cerebrospinal fluid (central injection) of TRP, an analog of thyrotropin-releasing hormone, which is a central mediator of the stress response to cold temperatures.31,32 This secretion is probably mediated by vagal activation of gastric enterochromaffin cells.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS modulation of gut–microbe signaling
What the sources say
- Not checked yetcites [31] Stephens, R. L. & Tache, Y. Intracisternal injection of a TRH analogue stimulates gastric luminal serotonin release in rats. Am. J. Physiol. 256, G377–G383 (1989).
- Not checked yetcites [32] Yang, H. et al. TRH analogue microinjected into specific medullary nuclei stimulates gastric serotonin secretion in rats. Am. J. Physiol. 262, G216–G222 (1992).
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, secretion of antimicrobial peptides, such as defensins, by Paneth cells has an important role in host defense mechanisms against inflammatory and infectious diseases of the gut.29”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS modulation of gut–microbe signaling
What the sources say
- Not checked yetcites [29] Salzman, N. H., Underwood, M. A. & Bevins, C. L. Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa. Semin. Immunol. 19, 70–83 (2007). source
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In the paper
“For example, Bifidobacterium bifidum and Lactobacillus acidophilus are able to promote motility, while Escherichia species can inhibit it.6”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Bidirectional signaling
What the sources say
- Not checked yetcites [6] Mazmanian, S. K. et al. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Several signaling molecules used by the host for neuronal and neuroendocrine signaling (for example, catecholamines, serotonin, dynorphin, and cytokines) are also likely to be secreted into the gut lumen by neurons, immune cells and enterochromaffin cells, and the CNS is likely to have an important role in the release of these molecules.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS modulation of gut–microbe signaling
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In the paper
“Similarly to eukaryotes, prokaryotes communicate with each other through hormones and hormone-like compounds. This pattern of mutual bacterial inter action is called quorum sensing.41”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Bidirectional signaling
What the sources say
- Not checked yetcites [41] Nealson, K. H., Platt, T. & Hastings, J. W. Cellular control of the synthesis and activity of the bacterial luminescent system. J. Bacteriol. 104, 313–322 (1970). source
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In the paper
“Autoinducer 3 binds to the bacterial membrane receptor QseC, which results in its autophosphorylation. QseC then phosphorylates its response regulator, QseB, to initiate a complex signaling cascade that activates the expression of bacterial genes associated with virulence and motility, including the gene that presides over flagellum development.34”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Bidirectional signaling
What the sources say
- Not checked yetcites [34] Hughes, D. T. & Sperandio, V. Inter-kingdom signalling: communication between bacteria and their hosts. Nat. Rev. Microbiol. 6, 111–120 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Stress-induced changes in permeability involve activation of glial and mast cells in the gut, overproduction of interferon-γ and changes in the morphology of the colonic epithelium via reduced expression of tight junction protein 2 (zona occludens 2) and by occlusion of important components of the intestinal tight junction.28”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS-related changes in gut environment
What the sources say
- Not checked yetcites [28] Demaude, J. et al. Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction. Gut 55, 655–661 (2006). source
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In the paper
“In vitro norepinephrine stimulates the growth of several strains of enteric pathogens (reviewed elsewhere34) and magnifies the virulent properties of Campylobacter jejuni.36”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > CNS modulation of gut–microbe signaling
What the sources say
- Not checked yetcites [34] Hughes, D. T. & Sperandio, V. Inter-kingdom signalling: communication between bacteria and their hosts. Nat. Rev. Microbiol. 6, 111–120 (2008). source
- Not checked yetcites [36] Cogan, T. A. et al. Norepinephrine increases the pathogenic potential of Campylobacter jejuni. Gut 56, 1060–1065 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, autoinducer 3 can stimulate nor epinephrine receptors on the surface of eukaryotic cells, and α-2 receptors are present on the brush border of human enterocytes.51”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Microbe–gut–brain signaling
What the sources say
- Not checked yetcites [51] Valet, P. et al. Characterization and distribution of alpha 2-adrenergic receptors in the human intestinal mucosa. J. Clin. Invest. 91, 2049–2055 (1993). 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
“Although the effects of enteric microbiota to host signaling on various gut functions, including motility, secretion and immune function, have been studied extensively in healthy and diseased states, the possible effect of such microbial signaling beyond the gastro intestinal tract and on the nervous system has received little attention.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Microbe–gut–brain signaling
hedged- Asserted: passes — The authors put it forward as true.
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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
“Microbial signaling molecules could interact directly with afferent nerve terminals in situations where intestinal permeability is enhanced (for example, during inflammation or stress) or their signal could be relayed to neurons within the intestinal wall by ‘transducer cells’ in the epithelium.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Microbe–gut–brain signaling
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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
“That signaling molecules are released by the host into the lumen of the gastrointestinal tract during stress and that receptors and intercellular signaling mechanisms for these same molecules are present on certain luminal microbes34 strongly suggests that the nervous system can also directly modulate microbial behavior.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Bidirectional signaling
What the sources say
- Not checked yetcites [34] Hughes, D. T. & Sperandio, V. Inter-kingdom signalling: communication between bacteria and their hosts. Nat. Rev. Microbiol. 6, 111–120 (2008). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Enterochromaffin cells are distributed throughout the intestinal tract,52 and, like intestinal epithelial cells, those located in the intestinal mucosa are accessible to the enteric microbiota on the intestinal lumen side, and are in contact with afferent and efferent nerve terminals located on the lamina propria.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enterochromaffin cells as signal transducers
What the sources say
- Not checked yetcites [52] Walsh, J. H. & Mayer, E. A. Gastrointestinal peptide hormones and signal transduction. In Gastrointestinal Disease: Pathophysiology, Diagnosis, Management 5th edn (Eds Sleizenger, M. & Fordtran, J.) 18–44 (WB Saunders, Philadelphia, 1993).
plain- Asserted: passes — The authors put it forward as true.
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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
“Similar mechanisms could have a role in the patho physiology of alterations in bowel habits for patients with IBS.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Microbe–gut–brain signaling
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“Thus, whereas the bacterial adrenergic agonist autoinducer 3 may mediate inhibition of intestinal fluid secretion—and thus delay transit rate—by binding to α-2 receptors on epithelial cells, other microbial factors may stimulate serotonin release by enterochromaffin cells to enhance fluid secretion, and thus accelerate transit rate.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enterochromaffin cells as signal transducers
hedgedconditional- 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
“This increase in luminal fluid in turn stimulates bowel motility, which ultimately helps remove intestinal contents, including pathogenic bacteria.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enterochromaffin cells as signal transducers
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
“Interestingly, olfactory and taste receptors are expressed in enterochromaffin cells, and odorants present in the luminal environment (probably produced by the enteric microbiota) are also able to effect serotonin release by these cells.53”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enterochromaffin cells as signal transducers
What the sources say
- Not checked yetcites [53] Braun, T., Voland, P., Kunz, L., Prinz, C. & Gratzl, M. Enterochromaffin cells of the human gut: sensors for spices and odorants. Gastroenterology 132, 1890–1901 (2007). 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
“Nerve terminals of vagal afferents are located in close proximity to enterochromaffin cells, and these terminals express the serotonin-specific receptor 5-HT3R.67”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Vagal transmission of luminal signals
What the sources say
- Not checked yetcites [67] Raybould, H. E., Cooke, H. J. & Christofi, F. L. Sensory mechanisms: transmitters, modulators and reflexes. Neurogastroenterol. Motil. 16 (Suppl. 1), 60–63 (2004). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“A mechanism of this type might explain the reported upregulation of mucosal serotonin in a mouse model of postinfectious bowel dysfunction.66”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enterochromaffin cells as signal transducers
What the sources say
- Not checked yetcites [66] Wheatcroft, J. et al. Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction. Neurogastroenterol. Motil. 17, 863–870 (2005). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The cholera toxin, a secretory enterotoxin from Vibrio cholerae, is known to trigger intestinal-fluid secretion by binding to the GM1 ganglioside on the surface of enterochromaffin cells. This interaction results in serotonin-mediated activation of secretomotor reflexes.61”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enterochromaffin cells as signal transducers
What the sources say
- Not checked yetcites [61] Lencer, W. I. Microbes and microbial toxins: paradigms for microbial-mucosal toxins. V. Cholera: invasion of the intestinal epithelial barrier by a stably folded protein toxin. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G781–G786 (2001). source
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
“Inflammation-induced upregulation of serotonin signaling persists after the inflammation has receded, and, in this post inflammatory, upregulated state, microbe to entero chromaffin cell signaling may result in persistent symptoms of bowel dysfunction in human, post infectious IBS.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enterochromaffin cells as signal transducers
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The influence on the brain of stimuli such as cytokines and vagal signaling has been well characterized in animal models of inflammation, and the constellation of psychological symptoms associated with inflammation (fatigue, social withdrawal and loss of appetite) has been labeled the sickness behavior syndrome.72”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enteric microbiota and homeostatic functions
What the sources say
- Not checked yetcites [72] Watkins, L. R. & Maier, S. F. The pain of being sick: implications of immune-to-brain communication for understanding pain. Annu. Rev. Psychol. 51, 29–57 (2000). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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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
“As afferent nerves are not exposed to the luminal side of the intestine, under normal circumstances sensory neurons are indirectly activated by stimuli in the intestinal lumen via paracrine signaling, which is mediated by compounds such as serotonin, cholecystokinin, histamine, secretin, somatostatin, melatonin, uroguanylin, and corticotrophin-releasing factor, all of which can be released from ne”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Vagal transmission of luminal signals
What the sources say
- Not checked yetcites [68] Schonhoff, S. E., Giel-Moloney, M. & Leiter, A. B. Minireview: development and differentiation of gut endocrine cells. Endocrinology 145, 2639–2644 (2004). source
- Not checked yetcites [69] O'Hara, J. R., Ho, W., Linden, D. R., Mawe, G. M. & Sharkey, K. A. Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G998–G1007 (2004). source
plaindirect- Asserted: passes — The authors put it forward as true.
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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 discussed earlier, in the presence of increased intestinal permeability (caused, for instance, by stress or gut inflammation), access of various bacterial products and inflammatory mediators to nerve endings in the mucosa would be a plausible mechanism for microbe to brain communication.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enteric microbiota and homeostatic functions
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. 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
“Possible mechanisms underlying such changes include effects secondary to the production of gas and short-chain fatty acids by enteric microbiota, and direct enteric microbiota to host signaling.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Clinical impact of bidirectional signaling
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Evidence of activation of the afferent vagal system was reported, which suggests a possible vagus-mediated microbe to brain signaling pathway.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enteric microbiota and homeostatic functions
What the sources say
- Not checked yetcites [73] Lyte, M., Li, W., Opitz, N., Gaykema, R. P. & Goehler, L. E. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium. Physiol. Behav. 89, 350–357 (2006). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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, in healthy organisms, signaling via epithelial transducer cells, such as enterochromaffin cells, may be the predominant mechanism.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Enteric microbiota and homeostatic functions
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.
In the paper
“In postinfectious IBS, major psychological stress around the time of gastroenteritis, trait anxiety, as well as extended duration of the infection, have been identified as risk factors for the persistence of symptoms.81”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Clinical impact of bidirectional signaling
What the sources say
- Not checked yetcites [81] Gwee, K. A. et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut 44, 400–406 (1999). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“One way to explain this resilience would be to consider the epithelium-associated biofilm as a permanent bacterial reservoir whose presence allows prompt reconstitution of the physiological microbiota profile in the gut lumen following a decline in luminal microbiota.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Clinical impact of bidirectional signaling
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.
- Rests on an assumption: The gastrointestinal system is surprisingly resilient to transient changes in enteric microbiota induced by antibiotic treatment, colonic lavage, or, possibly, by spikes in psychological stress.
In the paper
“This reduction in abdominal girth was associ ated with an acceleration of orocecal as well as colonic transit and with an overall improvement in symptoms.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Potential therapeutic implications
What the sources say
- Not checked yetcites [13] Agrawal, A. et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173-010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment. Pharmacol. Ther. (In press).
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- 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
“Inflammation-induced upregulation of the mucosal serotonin signaling system would be expected to enhance the ability of the enteric microbiota to modulate gut motility through activation of peristaltic and secretomotor reflexes.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Clinical impact of bidirectional signaling
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Evidence suggests that modification of the enteric microbiota by administration of antibiotics, probiotic bacteria or prebiotic substances (for example, certain fibers or lactulose) are beneficial in the treatment of IBD14 and improve some symptoms of IBS.12”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Potential therapeutic implications
What the sources say
- Not checked yetcites [14] Vanderpool, C., Yan, F. & Polk, D. B. Mechanisms of probiotic action: implications for therapeutic applications in inflammatory bowel diseases. Inflamm. Bowel Dis. 14, 1585–1596 (2008). source
- Not checked yetcites [12] Spiller, P. Review article: probiotics and prebiotics in irritable bowel syndrome (IBS). Aliment. Pharmacol. Ther. (2008).
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Little is known about the possible role of direct signaling by luminal microorganisms to the brain in healthy and diseased states.
“However, little is known about the possible role of direct signaling by luminal microorganisms to the brain in healthy and diseased states.”
The paper relies on this without support.
The gastrointestinal system is surprisingly resilient to transient changes in enteric microbiota induced by antibiotic treatment, colonic lavage, or, possibly, by spikes in psychological stress.
“Notably, despite the intriguing possibility of adverse clinical consequences of long-term functional disruption in the brain–gut–microbe axis, the gastro intestinal system is surprisingly resilient to transient changes in enteric microbiota induced by antibiotic treatment, colonic lavage, or, possibly, by spikes in psychological stress.”
Claims other papers make about this one
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The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Microbes can communicate with each other via metabolites, similar to those recognized by host cells and can thereby interact with gut ANS synapses (Rhee et al., 2009).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Rhee et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The size and quality of the intestinal mucus layer is believed to be mediated by sympathetic innervation where mucosal immune system modulation (Elenkov et al., 2000) and microbial composition and behavior alterations (commensal and pathogenic) were seen (Macfarlane and Dillon, 2007;Rhee et al., 2009)”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Rhee et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The concept of the microbiota-gut-brain axis thus emerged (Cryan and O'Mahony, 2011;De Palma et al., 2014;Rhee et al., 2009) based upon the rich historical legacy of the illustrious scientific figures discussed above, amongst many others.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Rhee et al., 2009
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Gut-brain communication can also be achieved through vagus nerve signaling (57).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [57]
In the citing paper
“By regulating gastrointestinal functions, e.g., motility, nutrient absorption, acid production and mucosal immunity, the brain shapes the gut habitat and therefore selects for a distinct microbial profile [62].”
In the citing paper
“There are evidence that the gut microbiota modulates the CNS via the ENS, the ANS, the HPA axis and vice versa [124,213]”
From Gut microbiota role in irritable bowel syndrome: New therapeutic strategies (2016) · cites this paper as [124]
In the citing paper
“Mounting evidence suggests that the gastrointestinal microbiota influences host behaviour via bi-directional communication through what has been coined the microbiota-gut-brain axis [17, 18, 20, 29, 50, 60, 71].”
From Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse (2020) · cites this paper as [60]
In the citing paper
“It has been also lately recognized that the gut-brain interactions might be essentially influenced by the gut microbiota (Borre et al., 2014;Grenham et al., 2011;Rhee et al., 2009).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Rhee et al., 2009
Citations
Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., & Gordon, J. I. (2007) · Nature · doi:10.1038/nature06244 · Cited by 6,091
Gut flora in health and disease
Guarner, F., & Malagelada, J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12489-0 · Cited by 3,480 · cited 1×
“Approximately 10 11 bacterial cells can be found per gram of colon contents”
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X., Kubo, C., & Koga, Y. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.063388 · Cited by 2,735 · cited 1×
“Inflammation-associated hyperalgesia induced by a variety of stimuli, including administration of proinflammatory cytokines, was less intense in germ-free mice than in conventional mice”
A microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340 · cited 1×
“The human gut harbors 400–1,000 different bacterial species”
Elenkov, I. J., Wilder, R. L., Chrousos, G. P., & Vizi, E. S. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01470-4 · Cited by 2,252
Gershon, M. D., & Tack, J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2006.11.002 · Cited by 1,563
O’Mahony, L., McCarthy, J., Kelly, P., Hurley, G., Luo, F., Chen, K., O’Sullivan, G. C., Kiely, B., Collins, J. K., Shanahan, F., et al. (2005) · Gastroenterology · doi:10.1053/j.gastro.2004.11.050 · Cited by 1,448
Cellular Control of the Synthesis and Activity of the Bacterial Luminescent System
Nealson, K. H., Platt, T., & Hastings, J. W. (1970) · Journal of Bacteriology · doi:10.1128/jb.104.1.313-322.1970 · Cited by 1,301 · cited 1×
“This pattern of mutual bacterial interaction is called quorum sensing”
Kassinen, A., Krogius-Kurikka, L., Mäkivuokko, H., Rinttilä, T., Paulin, L., Corander, J., Malinen, E., Apajalahti, J., & Palva, A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.04.005 · Cited by 1,002 · cited 1×
“A departure from the physiological balance of the enteric microbiota has been suggested as a factor in the pathophysiology of IBS, a condition in which abnormal gastrointestinal motility and secretion is implicated as a cause of alterations in bowel habits”
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Cited by
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Items 601–700 of 999
The Gut Microbiota–Brain Axis Expands Neurologic Function: A Nervous Rapport
Bauer, K. C., Rees, T., & Finlay, B. B. (2019) · BioEssays · doi:10.1002/bies.201800268 · Cited by 26
Gut Microbiota between Environment and Genetic Background in Familial Mediterranean Fever (FMF)
Ciaula, A. D., Stella, A., Bonfrate, L., Wang, D. Q. ‐., & Portincasa, P. (2020) · Genes · doi:10.3390/genes11091041 · Cited by 25
Radiation-induced multi-organ injury
Molinar‐Inglis, O., DiCarlo, A. L., Lapinskas, P. J., Rios, C. I., Satyamitra, M. M., Silverman, T., Winters, T. A., & Cassatt, D. R. (2024) · International Journal of Radiation Biology · doi:10.1080/09553002.2023.2295298 · Cited by 26
“A bidirectional ‘gut-brain axis’ has been described, where enteric microbiota interact with GI epithelium, sending signals to the brain to affect gut function and overall health (Rhee et al. 2009).”
BackgroundThe Interactome Hypothesis of Depression
Cocchi, M., Gabrielli, F., Tonello, L., & Pregnolato, M. (2010) · NeuroQuantology · doi:10.14704/nq.2010.8.4.318 · Cited by 24
“Serotonin appears to be a central physiological mediator of the braingut connection (Rhee, 2009).”
BackgroundColombetti, G., & Zavala, E. (2019) · Biology & Philosophy · doi:10.1007/s10539-019-9699-6 · Cited by 33
“In addition, interactions between brain, gastrointestinal tract, and gut microbiota appear to be mediated by other bodily systems—such as the enteric nervous system and the immune system (Rhee et al. 2009; Konturek et al. 2011; Lyte et al. 2011).”
BackgroundValent, D., Arroyo, L., Fàbrega, E., Font‐i‐Furnols, M., Rodrı́guez-Palmero, M., Moreno-Muñoz, J. A., Tibau, J., & Bassols, A. (2020) · Beneficial Microbes · doi:10.3920/bm2019.0197 · Cited by 24
Redondo-Flórez, L., Fernández‐Lucas, J., & Clemente‐Suárez, V. J. (2020) · Nutrients · doi:10.3390/nu12123644 · Cited by 26
Metabolic Profiling in Bipolar Disorder Patients During Depressive Episodes
Ren, Y., Bao, S., Jia, Y., Sun, X., Cao, X.-X., Bai, X., Tian, J., & Yang, H. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.569612 · Cited by 25
“Some studies found that there is a biphasic signal transduction system in the brain and gut microbiota, which is named the microbiota-gut-brain axis (36).”
BackgroundStress and the Role of the Gut–Brain Axis in the Pathogenesis of Schizophrenia: A Literature Review
Vafadari, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189747 · Cited by 25
“Stress-related psychiatric symptoms, such as stressful behaviors, and gastrointestinal disorders, such as irritable bowel syndrome, show the significant importance of the pathophysiology of the brain–gut axis [44,46,47].”
BackgroundAlterations of the gut microbiota in patients with schizophrenia
Li, Z., Tao, X., Wang, D., Pu, J., Liu, Y., Gui, S., Zhong, X., Yang, D., Zhou, H., Tao, W., et al. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1366311 · Cited by 26
“The MGB establishes a bidirectional communication system between the central nervous system and gut microbiota, mediated by neural, immune, and endocrine pathways, thereby exerting in fl uences on brain function (14, 15).”
BackgroundAutism and Gut–Brain Axis: Role of Probiotics
Chidambaram, S. B., Tuladhar, S., Bhat, A., Mahalakshmi, A. M., Ray, B., Essa, M. M., Bishir, M., Bolla, S. R., Nanjaiah, N. D., Guillemin, G. J., et al. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-30402-7_21 · Cited by 23
Kiełbik, P., & Witkowska‐Piłaszewicz, O. (2024) · Animals · doi:10.3390/ani14142048 · Cited by 27
“The gut–brain axis is composed of immunological, metabolic, endocrinological, and neuronal mediators [48].”
BackgroundBaj, A., Bistoletti, M., Bosi, A., Moro, E., Giaroni, C., & Crema, F. (2019) · Toxins · doi:10.3390/toxins11080449 · Cited by 23
“Indeed, it is well established that the stress-induced activation of the hypothalamic–pituitary adrenal (HPA) axis, via the hormonal cascade represented by corticotrophin-releasing factor (CRF), adenocorticotrophin hormone (ACTH), and cortisol, has an important role in the regulation of several functions of the brain–…”
BackgroundKamiński, M., Skonieczna‐Żydecka, K., Łoniewski, I., Koulaouzidis, A., & Marlicz, W. M. (2019) · Gastroenterology Review · doi:10.5114/pg.2019.86747 · Cited by 24
“Possible involvement of microbiota in chronic constipation Gut microbiota affect the structure and function of the central nervous system due to interactions with enterochromaffin cells and vagal afferent nerve pathways [52, 53].”
BackgroundAltered physiology of gastrointestinal vagal afferents following neurotrauma
Blanke, E. N., Holmes, G. M., & Besecker, E. M. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.290883 · Cited by 26
“The bidirectional pathway or the microbiota-gut-brain axis (Rhee et al., 2009; Bercik, 2011; Cryan and O’Mahony, 2011; Cryan and Dinan, 2012; Burokas et al., 2015; Mayer et al., 2015) is emerging as a critical communication line between the GI microbiome and brain (Sherwin et al., 2018) via the VN,…”
BackgroundAssessment of the gut bacterial microbiome and metabolome of girls and women with Rett Syndrome
Thapa, S., Venkatachalam, A., Khan, N., Naqvi, M., Balderas, M. A., Runge, J. K., Haag, A. M., Hoch, K. M., Glaze, D. G., Luna, R. A., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0251231 · Cited by 23
Sinagra, E., Pellegatta, G., Guarnotta, V., Maida, M. F., Rossi, F., Conoscenti, G., Pallio, S., Alloro, R., Raimondo, D., Pace, F., et al. (2021) · Life · doi:10.3390/life11070715 · Cited by 23
“It leads to a persistently stimulation of proinflammatory condition and macrophage/monocyte infiltration in the gut [3].”
BackgroundZhang, S., Qian, Y., Li, Q., Xu, X., Li, X., Wang, C., Cai, H., Zhu, J., & Yu, Y. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.750704 · Cited by 24
“Based on a review of the literature (Rhee et al., 2009; Dinan and Cryan, 2017; Martin et al., 2018; Cryan et al., 2019), 33 brain-related metabolic pathways (Supplementary Table 1) were selected and 5http://www.genome.jp/kegg/ Frontiers in Neuroscience | www.frontiersin.org 4 October 2021 | Volume…”
BackgroundAn anxious relationship between Autism Spectrum Disorder and Gut Microbiota: A tangled chemistry?
Vellingiri, B., Aishwarya, S. Y., Jancy, S. B., Abhishek, G. S., Babu, H. W. S., Vijayakumar, P., Narayanasamy, A., Mariappan, S., Sangeetha, R., Gopalakrishnan, A. V., et al. (2022) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2022.03.003 · Cited by 23
Gut dysmotility in children with neurological impairment: the nutritional management
Corsello, A., Scatigno, L., Govoni, A., Zuccotti, G., Gottrand, F., Romano, C., & Verduci, E. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1200101 · Cited by 26
“The gut-brain axis modulates GI motility, gastric secretion, blood flow, gut barrier integrity, immune response, and visceral sensations (7, 8).”
BackgroundOptimizing the Gut Microbiota for Individualized Performance Development in Elite Athletes
Nolte, S., Krüger, K., Lenz, C., & Zentgraf, K. (2023) · Biology · doi:10.3390/biology12121491 · Cited by 28
“The connection between the enteric nervous system and the gut mainly goes through the vagus nerve [144], hormones [145], and microbial metabolites [146,147].”
BackgroundBuckley, M. M., & O’Malley, D. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00112 · Cited by 23
“Communication between the gastrointestinal (GI) tract and the brain, or the “gut-brain axis” utilizes endocrine (Gareau et al., 2008; Rhee et al., 2009) and immune mediators (Öhman et al.”
BackgroundNeijat, M., Shirley, R. B., Welsher, A., Barton, J., Thiery, P., & Kiarie, E. G. (2019) · Poultry Science · doi:10.3382/ps/pez080 · Cited by 24
Forsyth, A., Raslan, K., Lyashenko, C., Bona, S., Snow, M., Khor, B., Herrman, E., Ortiz, S., Choi, D., Maier, T., et al. (2019) · Human Microbiome Journal · doi:10.1016/j.humic.2019.100066 · Cited by 23
O’Connor, K. M., Lucking, E. F., Cryan, J. F., & O’Halloran, K. D. (2020) · The Journal of Physiology · doi:10.1113/jp280279 · Cited by 23
“Whereas the influence of the gut microbiota on the brain and behaviour is well recognised (Dinan & Cryan, 2017), there is emerging evidence that the gut microbiota may also serve as a major player in homeostatic neurocontrol systems critical for life, through a bidirectional pathway termed the microbiota–gut–brain axi…”
BackgroundPhytonutrients and their neuroprotective role in brain disorders
Adhikary, K., Ganguly, K., Sarkar, R., Abubakar, M., Banerjee, P., & Karak, P. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1607330 · Cited by 26
Microbiota Involvement in the Gut–Brain Axis
Indrio, F., Riezzo, G., Raimondi, F., Mauro, A. D., & Francavilla, R. (2013) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/01.mpg.0000441927.20931.d6 · Cited by 22
“The gut–brain interaction is a complex bidirectional communication system that exists between the central nervous system (CNS) and the GI tract (20).”
BackgroundA review of functional gastrointestinal disorders: A primer for mental health professionals
Chandran, S., Prakrithi, S., Mathur, S., Kishor, M. R., & Rao, T. S. (2018) · Archives of Mental Health · doi:10.4103/amh.amh_25_18 · Cited by 21
Chait, Y. A., Mottawea, W., Tompkins, T. A., & Hammami, R. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110182 · Cited by 22
Parkinson’s Disease: A Prionopathy?
Vascellari, S., & Manzin, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158022 · Cited by 26
Aberrant Gut-To-Brain Signaling in Irritable Bowel Syndrome - The Role of Bile Acids
Dhonnabháín, R. N., Xiao, Q., & O’Malley, D. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.745190 · Cited by 25
Li, C., Ye, F., Xu, C.-X., Jiang, N., Chang, Q., Liu, X., & Pan, R. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.02.008 · Cited by 29
Phage Interactions with the Nervous System in Health and Disease
Jędrusiak, A., Fortuna, W., Majewska, J., Górski, A., & Jończyk‐Matysiak, E. (2023) · Cells · doi:10.3390/cells12131720 · Cited by 25
Effects of Peanuts and Pistachios on Gut Microbiota and Metabolic Syndrome: A Review
Campos, S. B., Filho, J. G. D. O., Salgaço, M. K., Jesus, M. H. D., & Egea, M. B. (2023) · Foods · doi:10.3390/foods12244440 · Cited by 22
Park, S. J., Kim, K. W., & Lee, E. J. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00994 · Cited by 27
“This understanding led to the expansion of the concept of the microbiota-gut-brain axis (Rhee et al., 2009; Bercik, 2011; Collins et al., 2012; Cryan et al., 2019).”
A future perspective on neurodegenerative diseases: nasopharyngeal and gut microbiota
Khan, F., & Oloketuyi, S. F. (2016) · Journal of Applied Microbiology · doi:10.1111/jam.13327 · Cited by 22
Gan, W. C., Smith, L. D., Luca, E., & Harnett, J. (2018) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2018.08.016 · Cited by 23
Adak, A., Ghosh, K., & Mondal, K. C. (2014) · PubMed · Cited by 22
Lv, K., Fan, Y., Xu, L., & Xu, M. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i20.3607 · Cited by 22
Mast Cells, Astrocytes, Arachidonic Acid: Do They Play a Role in Depression?
Traina, G., & Cocchi, M. (2020) · Applied Sciences · doi:10.3390/app10103455 · Cited by 20
Fu, K., Zhang, D., Song, Y., Xu, M., Wu, R., Xiong, X., Liu, X., Wu, L., Guo, Y., Zhou, Y. L., et al. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/2251679 · Cited by 21
“Several signal molecules (such as catecholamines, serotonin, dynorphin, and cytokines) used by the host for nerve and neuroendocrine signal transduction may also be secreted into the intestinal lumen by neurons, immune cells, and enterochromaffin cells for the gut-brain bidirectional communication [12].”
BackgroundYoshioka, T., Ohashi, M., Matsumoto, K., Omata, T., Hamano, T., Yamazaki, M., Kimiki, S., Okano, K., Kobayashi, R., Yamada, D., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.993132 · Cited by 21
Lee, A., Lee, J. Y., Jung, S.-W., Shin, S. Y., Ryu, H. S., Jang, S.-H., Kwon, J. G., & Kim, Y. S. (2023) · Korean Journal of Gastroenterology · doi:10.4166/kjg.2023.028 · Cited by 26
Gut Microbiota Modulation of Short Bowel Syndrome and the Gut–Brain Axis
Carter, J., Bettag, J., Morfin, S., Manithody, C., Nagarapu, A., Jain, A., Nazzal, H., Prem, S., Unes, M., McHale, M., et al. (2023) · Nutrients · doi:10.3390/nu15112581 · Cited by 21
“These are postulated to occur as a result of reduced expression of tight junction protein 2 (zona occludens 2) and by components of the intestinal tight junction modulation [52].”
BackgroundEvaluation of antibiotic-induced behavioral changes in mice
Kwon, H., Mohammed, A. E., Eltom, K. H., Albrahim, J. S., & Alburae, N. A. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113015 · Cited by 21
Donovan, H. S., Thomas, T. H., Campbell, G. B., Boisen, M. M., Rosenblum, L., Edwards, R. P., Bovbjerg, D. H., & Horn, C. C. (2016) · Supportive Care in Cancer · doi:10.1007/s00520-015-3071-4 · Cited by 23
“, diarrhea, constipation, and cramping) [5].”
Collyer, R., Clancy, A., & Borody, T. (2020) · Medicine in Microecology · doi:10.1016/j.medmic.2020.100029 · Cited by 19
Woloszynek, S., Pastor, S. J., Mell, J. C., Nandi, N., Sokhansanj, B. A., & ROSEN, G. L. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.01.003 · Cited by 20
Associations Between the Gut Microbiota and Internalizing Behaviors in Preschool Children
van de Wouw, M., Wang, Y., Workentine, M. L., Vaghef‐Mehrabany, E., Dewey, D., Reimer, R. A., Tomfohr‐Madsen, L. M., & Giesbrecht, G. F. (2021) · Psychosomatic Medicine · doi:10.1097/psy.0000000000001026 · Cited by 23
Reinold, J., Farahpour, F., Schoerding, A.-K., Fehring, C., Dolff, S., Konik, M., Korth, J., van Baal, L., Buer, J., Witzke, O., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.848650 · Cited by 20
Impairment of the gut health in Danio rerio exposed to triclocarban
Yan, Z., Du, J., Zhang, T., Sun, Q., Sun, B., Zhang, Y., & Li, S. (2022) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2022.155025 · Cited by 20
The role and molecular mechanism of gut microbiota in Graves’ orbitopathy
Li, Y., Luo, B., Tong, B., Xie, Z., Cao, J., Bai, X., Peng, Y., Wu, Y., Wang, W., & Qi, X. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01902-7 · Cited by 20
Gastrointestinal Microbiome and Multiple Health Outcomes: Umbrella Review
Chang, C., Yuan, X., Zhang, X., Chen, X., & Li, K. (2022) · Nutrients · doi:10.3390/nu14183726 · Cited by 22
Uncovering the core principles of the gut-lung axis to enhance innate immunity in the chicken
Saint-Martin, V., Quéré, P., Trapp, S., & Guabiraba, R. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.956670 · Cited by 22
“Emerging evidence in humans and mice suggests that the immunoregulatory function of the GM also pertains to distal organ sites including the airways and the brain (10, 11).”
BackgroundThe Brain, the Eating Plate, and the Gut Microbiome: Partners in Migraine Pathogenesis
Gazerani, P., Papetti, L., Dalkara, T., Cook, C. L., Webster, C., & Bai, J. (2024) · Nutrients · doi:10.3390/nu16142222 · Cited by 22
“…initiation of the Human Microbiome Project in 2007 [42,43], the microbiome–gut–brain (MGB) axis, a bidirectional communication network between the gut and the brain [44], has been a central focus in understanding the mechanisms of neurocognitive and psychological effects of gut–brain communication.”
BackgroundBioethics and the Hypothesis of Extended Health
Morar, N., & Skorburg, J. A. (2018) · Kennedy Institute of Ethics journal · doi:10.1353/ken.2018.0020 · Cited by 23
Jarras, H., Bourque, M., Poirier, A.-A., Morissette, M., Coulombe, K., Paolo, T. D., & Soulet, D. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12782 · Cited by 20
Bidirectional regulation of the brain–gut–microbiota axis following traumatic brain injury
You, X., Niu, L., Fu, J., Ge, S., Shi, J., Zhang, Y., & Zhuang, P. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00088 · Cited by 23
Tamayo, M., Agustí, A., Molina-Mendoza, G. V., Rossini, V., Francés‐Cuesta, C., Tolosa-Enguís, V., & Sanz, Y. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.12.028 · Cited by 20
Biological role of zonulin: a biomarker of increased intestinal permeability syndrome
Хавкин, А. И., Богданова, Н. М., & Новикова, В. П. (2021) · Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) · doi:10.21508/1027-4065-2021-66-1-31-38 · Cited by 22
Blecharz‐Klin, K., Świerczyńska, M., Piechal, A., Wawer, A., Joniec‐Maciejak, I., Pyrzanowska, J., Wojnar, E., Zawistowska‐Deniziak, A., Sulima-Celińska, A., Młocicki, D., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010330 · Cited by 22
Gastrointestinal Changes and Alzheimer's Disease
Sohrabi, M., Sahu, B., Kaur, H., Hasler, W. A., Prakash, A. K., & Combs, C. K. (2022) · Current Alzheimer Research · doi:10.2174/1567205019666220617121255 · Cited by 18
Viral Gastroenteritis: Sickness Symptoms and Behavioral Responses
Hellysaz, A., Neijd, M., Vesikari, T., Svensson, L., & Hagbom, M. (2023) · mBio · doi:10.1128/mbio.03567-22 · Cited by 22
“The gut-brain axis is a bidirectional communication between the central and the enteric nervous systems (CNS and ENS, respectively) (25), which provide the means to main-”
BackgroundGut microbiota, a hidden protagonist of traditional Chinese medicine for acute ischemic stroke
Gao, L., Xia, X., Shuai, Y., Zhang, H., Jin, W., Zhang, X., & Zhang, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1164150 · Cited by 20
“Disorders of the gut microbiota can also damage the gut mucosal barrier, leading to the spread of harmful toxins and bacteria into the peripheral organs, causing infections and even sepsis (Crapser et al., 2016; Roubalová et al., 2020).”
BackgroundJacobs, J. P., Sauk, J. S., Ahdoot, A., Liang, F., Katzka, W. R., Ryu, H. J., Khandadash, A., Lagishetty, V., Labus, J. S., Naliboff, B. D., et al. (2023) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izad185 · Cited by 20
Self-citationDu, J., Hu, Y., Li, Z., Zhou, J., Xiang, F., Zheng, H., & Xiao, H. (2023) · Environmental Toxicology and Chemistry · doi:10.1002/etc.5767 · Cited by 21
“The gut bacterial community is a key node of the brain – gut axis (Rhee et al., 2009).”
BackgroundProbiotic and microbiota engineering for practical applications
Moon, T. S. (2024) · Current Opinion in Food Science · doi:10.1016/j.cofs.2024.101130 · Cited by 19
Good girl goes bad: Understanding how gut commensals cause disease
Dey, P. (2024) · Microbial Pathogenesis · doi:10.1016/j.micpath.2024.106617 · Cited by 19
Jin, K., Chen, B., Han, S., Dong, J., Cheng, S., Qin, B. Y., & Lü, J. (2024) · Research · doi:10.34133/research.0384 · Cited by 21
Ruggles, A., & Benakis, C. (2024) · Cells · doi:10.3390/cells13100803 · Cited by 19
“Signaling from the brain can modulate the immune response in the gut, intestinal permeability, and bacterial–host interactions [161].”
BackgroundRoles of the gut microbiota in human neurodevelopment and adult brain disorders
Mallick, R., Basak, S., Das, R. K., Banerjee, A., Paul, S., Pathak, S., & Duttaroy, A. K. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1446700 · Cited by 54
Zhang, C., Liu, Y., Chen, S., Qiao, Y., Zheng, Y., Xu, M., Wang, Z., Hou, J., Wang, J., & Fan, H. (2019) · Viruses · doi:10.3390/v11060518 · Cited by 19
“Nervous and immune system exert critical control over microbiota composition [10,49].”
BackgroundCorrelation between Gut Microbiota and Six Facets of Neuroticism in Korean Adults
Park, E., Yun, K. E., Kim, M.-H., Kim, J., Chang, Y., Ryu, S., Kim, H., Kim, H., & Jung, S. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11121246 · Cited by 20
“Recently, the importance of the gut microbiome in human health has been in the spotlight [11].”
BackgroundEarly-life stress and the gut microbiome: A comprehensive population-based investigation
Mulder, R. H., Kraaij, R., Schuurmans, I. K., Francés‐Cuesta, C., Sanz, Y., Medina‐Gómez, C., Duijts, L., Rivadeneira, F., Tiemeier, H. W., Jaddoe, V. W. V., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.02.024 · Cited by 20
“The gastrointestinal system is encompassed by the enteric nervous system, which communicates with the central nervous system (Breit et al., 2018; Rhee et al., 2009).”
BackgroundHan, J. H., Rey, F. E., & Denu, J. M. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110521 · Cited by 21
“Although we did not directly assess gut microbiome composition in this study, it is well documented that diet modulates microbial composition and function (11, 113, 114) and elevated dietary choline can enrich TMA-producing bacteria (115, 116).”
Zhao, L., Geng, Z., Wang, Y., Wen, J., & Liu, D. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47100842 · Cited by 18
“Emerging evidence shows that disruptions in the gut–brain axis are associated with the pathogenesis of various diseases [96], including IBD, multiple sclerosis (MS), and ASD [97].”
Wang, Y., Zhang, J., Deji, C., Fan, J., Miao, X., Li, S. C., Zeng, X., & Guan, F. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24963 · Cited by 18
“Thus, as a potent psychostimulant, METH could modulate the gut microbiome profiles directly by impairing gut epithelial integrity (Rhee et al., 2009) or indirectly through the neuroendocrine or vagus nerve systems.”
BackgroundCabral, G. F., Schaan, A. P., Cavalcante, G. C., Sena-dos-Santos, C., de Souza, T. P., Port’s, N. M. D. S., Pinheiro, J. A. D. S., Ribeiro‐dos‐Santos, Â., & Vidal, A. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189839 · Cited by 18
Sun, Q., Ho, C., Zhang, X., Liu, Y., Zhang, R., & Wu, Z. (2022) · Food & Function · doi:10.1039/d1fo02716f · Cited by 19
Michels, M., Jesus, G. F. A., Abatti, M. R., Córneo, E. D. S., Cucker, L., Borges, H. D. M., Matos, N. D. S., Rocha, L. B., Dias, R., Simon, C. S., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02906-3 · Cited by 21
“The literature reports a series of evidence that the intestinal microbiota communicate with the central nervous system (CNS) through the gut–brain axis, possibly through neural, endocrine and immune pathways [14], where interactions in gut–brain axis are associated with intestinal inflammation, chronic abdominal pain…”
BackgroundKrela‐Kaźmierczak, I., Zakerska‐Banaszak, O., Skrzypczak-Zielińska, M., Łykowska‐Szuber, L., Szymczak‐Tomczak, A., Zawada, A. E., Rychter, A. M., Ratajczak, A. E., Skoracka, K., Skrzypczak, D., et al. (2022) · Nutrients · doi:10.3390/nu14122520 · Cited by 18
The cloacal microbiome of a cavity-nesting raptor, the lesser kestrel (Falco naumanni)
Costanzo, A., Ambrosini, R., Franzetti, A., Romanò, A., Cecere, J. G., Morganti, M., Rubolini, D., & Gandolfi, I. (2022) · PeerJ · doi:10.7717/peerj.13927 · Cited by 18
Kumar, H. S., Wisner, A. S., Refsnider, J. M., Martyniuk, C. J., & Zubcevic, J. A. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1186645 · Cited by 20
Zhou, C., Chen, Y., Xue, S., Shi, Q., Guo, L., Yu, H., Xue, F., Cai, M., Wang, H., & Peng, Z. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14287 · Cited by 17
Lou, H., Liu, X., & Liu, P. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1143827 · Cited by 20
“The gut microbiota regulates brain development and function through neurological, neuroimmune and neuroendocrine pathways, and conversely, the brain interacts with microbes through these pathways (Rhee et al., 2009).”
BackgroundImpact of Enteric Nervous Cells on Irritable Bowel Syndrome: Potential Treatment Options
Pastras, P., Aggeletopoulou, I., & Triantos, C. K. (2024) · Microorganisms · doi:10.3390/microorganisms12102036 · Cited by 18
“The ENS has been referred to as the “second brain” by researchers such as Furness and Stebbing because it can manage most aspects of digestion and gut defense independently of conscious sensation, allowing the CNS to focus on higher cognitive functions [33,44].”
BackgroundThe human gastrointestinal microbiota—An unexplored frontier for pharmaceutical discovery
Roeselers, G., Bouwman, J., Venema, K., & Montijn, R. C. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.09.007 · Cited by 18
Cheng, M., & Pan, T. (2016) · Pharmaceutical Biology · doi:10.1080/13880209.2016.1253109 · Cited by 18
“Gut microbiota and probiotics secrete signalling molecules that can regulate important functional mechanisms involved in brain activity, the mucosal immune system, and enterochromaffin cell-mediated vagal activation (Rhee et al. 2009; Cryan & Dinan 2012; Nicholson et al. 2012; Tillisch et al. 2013).”
BackgroundReese, A. T., & Carmody, R. N. (2018) · Applied and Environmental Microbiology · doi:10.1128/aem.02246-18 · Cited by 19
“The gut microbiota plays a crucial role in colonization resistance (186), it modulates the immune system (4), and it produces or alters host production of signaling molecules, with effects on organs as distant as the brain (187, 188).”
BackgroundIsaiah, S., Loots, D. T., Solomons, R., van der Kuip, M., van Furth, A. M., & Mason, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00296 · Cited by 20
Treating the Metabolic Syndrome by Fecal Transplantation—Current Status
Malnick, S. D. H., Fisher, D. L., Somin, M., & Neuman, M. G. (2021) · Biology · doi:10.3390/biology10050447 · Cited by 18
“Furthermore, bi-directional gut–brain interactions have an important effect on several aspects of the functioning of the GI tract [37].”
BackgroundHomolak, J., Perhoč, A. B., Knezović, A., Barilar, J. O., Koç, F., Stanton, C., Ross, R. P., & Šalković‐Petrišić, M. (2021) · Neuroendocrinology · doi:10.1159/000519988 · Cited by 19
Cerroni, R., Pietrucci, D., Teofani, A., Chillemi, G., Liguori, C., Pierantozzi, M., Unida, V., Selmani, S., Mercuri, N. B., & Stefani, A. (2022) · Brain Sciences · doi:10.3390/brainsci12060739 · Cited by 18
“The concept of “gut–brain axis”, a bidirectional channel of influence and communication between the brain and the enteric nervous system (ENS), was first introduced in the late 2000s [1].”
BackgroundMaity, C., Adak, A., Pathak, T. K., Pati, B. R., & Mondal, K. C. (2012) · Journal of Microbiology Immunology and Infection · doi:10.1016/j.jmii.2011.12.002 · Cited by 17
Immunity orchestrates a bridge in gut-brain axis of neurodegenerative diseases
Cheng, Y., Chen, C., & Zhang, F. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101857 · Cited by 19
Hu, W., Li, P., Zeng, N., & Tan, S. (2023) · Scientific Reports · doi:10.1038/s41598-023-27459-w · Cited by 19
Gut microbiota of Parkinson’s disease in an appendectomy cohort: a preliminary study
Nakahara, K., Nakane, S., Ishii, K., Ikeda, T., & Ando, Y. (2023) · Scientific Reports · doi:10.1038/s41598-023-29219-2 · Cited by 18
Minding the gut: extending embodied cognition and perception to the gut complex
Boem, F., Greslehner, G. P., Konsman, J. P., & Chiu, L. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1172783 · Cited by 17
Tănăsescu, R., & Constantinescu, C. S. (2014) · Current topics in behavioral neurosciences · doi:10.1007/7854_2014_361 · Cited by 19
On the estimation of metabolic profiles in metagenomics
Aßhauer, K. P., & Meinicke, P. (2013) · DROPS (Schloss Dagstuhl – Leibniz Center for Informatics) · doi:10.4230/oasics.gcb.2013.1 · Cited by 17
Metadata
- Authors
- Rhee, S. H., Pothoulakis, C., & Mayer, E. A.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Mayer, Emeran A.
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2009-05
- Volume
- 6
- Issue
- 5
- Pages
- 306-314
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC3817714
- OpenAlex
- W2076087096
- Semantic Scholar
- 8d46dbee61595ddb88b690b9979d376a39c691fe
- Cited by
- 1,342
- References
- 87
- Citations by year
- 2026: 66 · 2025: 107 · 2024: 112 · 2023: 130 · 2022: 122 · 2021: 127 · 2020: 114 · 2019: 90 · 2018: 84 · 2017: 94 · 2016: 77 · 2015: 48 · 2014: 55 · 2013: 45 · 2012: 33
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK033506, P01 DK-33506, R01 DK072471, R01 DK 48351, R01DK048351, R01-DK47343, P50DK064539, P-50DK64539, R01DK047343, R01DK060729)
- National Center for Complementary and Integrative Health (R24AT002681)
- 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 › Neurology › Vagus Nerve Stimulation Research
- Keywords
- gut-brain axis, gut microbiota, enteric microbiota, two-way communication, central nervous system, enterochromaffin cells, intestinal permeability, lamina propria, gastrointestinal motility, gastrointestinal secretion, functional bowel disorders, inflammatory bowel disease
- MeSH terms
- Brain, Humans, Intestines, Inflammatory Bowel Diseases, Enteric Nervous System
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).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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