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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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
“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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It may state two separate claims as one.
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.
- 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.
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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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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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- 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
“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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- 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.
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
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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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Items 401–500 of 999
What’s bugging your teen?—The microbiota and adolescent mental health
McVey Neufeld, K.-A., Luczynski, P., Seira Oriach, C., Dinan, T. G., & Cryan, J. F. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.005 · Cited by 56
“In the last decade, the concept of this axis has been extended to the “microbiota-gut-brain axis”, a reflection of our increased understanding of the importance of the trillions of bugs residing and working in the human gut (Rhee et al., 2009; Bercik, 2011; Cryan and O'Mahony, 2011).”
Hsiung, R.-T., Fang, W., LePage, B. A., Hsu, S.-A., Hsu, C., & Chou, J. (2020) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-020-09661-8 · Cited by 58
Gut microbiota in chronic pain: Novel insights into mechanisms and promising therapeutic strategies
Liu, L., Wu, Q. J., Chen, Y., Ren, H., Zhang, Q., Yang, H., Zhang, W., Ding, T., Wang, S., Zhang, Y., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.109685 · Cited by 57
Garofalo, C., Cristiani, C. M., Ilari, S., Passacatini, L. C., Malafoglia, V., Viglietto, G., Maiuolo, J., Oppedisano, F., Palma, E., Tomino, C., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11061701 · Cited by 68
The Brain–Gut–Microbiome Axis in Psychiatry
Jang, S.-H., Woo, Y. S., Lee, S.-Y., & Bahk, W. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197122 · Cited by 59
“It coordinates and integrates gastrointestinal function in addition to connecting the brain to peripheral functions [1].”
BackgroundAllen, R. G., Lafuse, W. P., Galley, J. D., Ali, M. M., Ahmer, B. M. M., & Bailey, M. T. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.11.002 · Cited by 55
Subramaniam, C. B., Bowen, J. M., Gladman, M. A., Lustberg, M. B., Mayo, S. J., & Wardill, H. R. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.07.002 · Cited by 59
The gut–brain axis in vertebrates: implications for food intake regulation
Blanco, A. M., Calo, J., & Soengas, J. L. (2021) · Journal of Experimental Biology · doi:10.1242/jeb.231571 · Cited by 60
Gut microbiota resilience in horse athletes following holidays out to pasture
Mach, N., Lansade, L., Bars‐Cortina, D., Dhorne‐Pollet, S., Foury, A., Moisan, M., & Ruet, A. (2021) · Scientific Reports · doi:10.1038/s41598-021-84497-y · Cited by 56
Role of the duodenal microbiota in functional dyspepsia
Brown, G., Hoedt, E. C., Keely, S., Shah, A., Walker, M. M., Holtmann, G., & Talley, N. J. (2022) · Neurogastroenterology & Motility · doi:10.1111/nmo.14372 · Cited by 58
Song, W., Zhang, M., Teng, L., Wang, Y., & Zhu, L. (2022) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001510 · Cited by 59
Diabetes-Related Dysfunction of the Small Intestine and the Colon: Focus on Motility
Horváth, V. J., Putz, Z., Izbéki, F., Körei, A. E., Gerő, L., Lengyel, C., Kempler, P., & Várkonyi, T. T. (2015) · Current Diabetes Reports · doi:10.1007/s11892-015-0672-8 · Cited by 57
Reframing the Teenage Wasteland: Adolescent Microbiota-Gut-Brain Axis
Neufeld, K. M., Luczynski, P., Dinan, T. G., & Cryan, J. F. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716635536 · Cited by 60
“In fact, the well-established gut-brain axis, or the bidirectional highway of communication connecting the gut and brain, has been recently extended to include the bacterial components of the intestinal lumen, leading to the now extended concept of a microbiota-gut-brain axis.(28-31) Mechanisms by which communication…”
BackgroundExploring the microbiome in health and disease
Scotti, E., Boué, S., Sasso, G. L., Zanetti, F., Belcastro, V., Poussin, C., Sierro, N., Battey, J. N. D., Gimalac, A., Ivanov, N. V., et al. (2017) · Toxicology Research and Application · doi:10.1177/2397847317741884 · Cited by 56
Resveratrol Modulates the Gut-Brain Axis: Focus on Glucagon-Like Peptide-1, 5-HT, and Gut Microbiota
Chung, J. Y., Jeong, J., & Song, J. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.588044 · Cited by 56
Microbiota-gut-brain axis and nutritional strategy under heat stress
Wen, C., Wei, S., Zong, X., Wang, Y., & Jin, M. (2021) · Animal nutrition · doi:10.1016/j.aninu.2021.09.008 · Cited by 56
“The disruption of the gutbrain axis may be involved in acute and chronic intestinal diseases (Mayer et al., 2014; Rhee et al., 2009).”
BackgroundImpact of intestinal disorders on central and peripheral nervous system diseases
El-Hakim, Y., Bake, S., Mani, K. K., & Sohrabji, F. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105627 · Cited by 54
Lactational Programming of Infant Behavioral Phenotype
Hinde, K. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4060-4_9 · Cited by 56
“Additionally along these pathways, commensal gut bacteria in fl uence neurobiological functioning and the HPA axis (Forsythe et al. 2010 ; Rhee et al. 2009 ) .”
BackgroundRole of fumaric acid in anti-inflammatory and analgesic activities of a Fumaria indica extracts
Shakya, A., Singh, G. K., Chatterjee, S. S., & Kumar, V. (2014) · Journal of Intercultural Ethnopharmacology · doi:10.5455/jice.20140912021115 · Cited by 54
The Gut and Nonmotor Symptoms in Parkinson's Disease
Klingelhoefer, L., & Reichmann, H. (2017) · International review of neurobiology · doi:10.1016/bs.irn.2017.05.027 · Cited by 53
Gut Microbiome and Modulation of CNS Function
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Comprehensive Physiology · doi:10.1002/cphy.c180031 · Cited by 53
“(103, 135) and functional gastrointestinal disorders, but in an expanding catalog of psychiatric and neurological conditions including mood and affect disorders, (31, 125), autism spectrum disorders (ASD) (31, 180), neurodegenerative disorders (142), multiple sclerosis (15), and chronic pain (3).”
Self-citationAlterations in gut microbiota are related to metabolite profiles in spinal cord injury
Jiang, J.-H., Ning, B., Kang, J.-N., Sun, Z.-F., Li, X., Zhang, X., Jin, Z., Zhang, C., Zhang, Y., Wang, H., et al. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.355769 · Cited by 54
“The bidirectional communication between the gut microbial system and the host central nervous system (CNS) is achieved through the microbe-gut-brain axis (MGBA), involving immune, endocrine, metabolic, and neural pathways (Rhee et al., 2009; Cryan and Dinan, 2012; Forsythe and Kunze, 2013; Janssen and Kersten, 2015; M…”
BackgroundFan, X., Zhang, Y., Song, Y., Zhao, Y., Xu, Y., Guo, F., Shao, M., Ma, X., Zhang, W., Wei, F., et al. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154656 · Cited by 53
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Guernier, V., Brennan, B., Yakob, L., Milinovich, G. J., Clements, A., & Magalhães, R. J. S. (2017) · BMC Infectious Diseases · doi:10.1186/s12879-016-2146-2 · Cited by 51
Making sense of gut feelings in the traumatic brain injury pathogenesis
Royes, L. F. F., & Gómez‐Pinilla, F. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.012 · Cited by 55
“The bidirectional communication between the central and the enteric nervous systems is crucial for modulation of gastrointestinal functions such as motility, secretion, blood flow, intestinal permeability, mucosal immune activity, and visceral sensation including pain (Rhee et al., 2009).”
BackgroundSalvo‐Romero, E., Stokes, P., Keogh, C. E., Brust‐Mascher, I., Hennessey, C., Knotts, T. A., Sladek, J. A., Rude, K. M., Swedek, M., Rabasa, G., et al. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00177.2020 · Cited by 56
Gut Microbiota‐Related Effects of Tanhuo Decoction in Acute Ischemic Stroke
Guo, Q., Jiang, X., Ni, C., Li, L., Chen, L., Wang, Y., Li, M., Wang, C., Gao, L. Q., Zhu, H., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5596924 · Cited by 54
“As gut microbiota participates in the bidirectional communication between the gut and the brain and modulates the hemostasis of hosts, the microbiota-gut-brain axis is fulfilled and plays an important role in brain injury, inflammation, and brain diseases [11, 21].”
Backgroundvan de Wouw, M., Walsh, C. J., Vigano, G. M. D., Lyte, J. M., Boehme, M., Gual‐Grau, A., Crispie, F., Walsh, A. M., Clarke, G. A., Dinan, T. G., et al. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.07.004 · Cited by 59
“…communication between the gastrointestinal microbiota and the brain, the microbiota-gutbrain axis may be playing a role in some of the symptoms of ASD (Rhee et al., 2009; Collins et al., 2012; Cryan and Dinan, 2012; Mayer et al., 2014; Foster et al., 2017; Cryan et al., 2019; Sherwin et al., 2019).”
BackgroundThe Gut-Brain-Immune Axis in Autism Spectrum Disorders: A State-of-Art Report
Puricelli, C., Rolla, R., Gigliotti, C. L., Boggio, E. M., Beltrami, E., Dianzani, U., & Keller, R. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.755171 · Cited by 64
“All these tasks are accomplished in concert with the autonomic, enteric, and neuroendocrine systems, with a contribution coming also from the hypothalamus-pituitaryadrenal axis (41, 42) (Figure 1).”
BackgroundCarloni, S., & Rescigno, M. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00955-3 · Cited by 57
Wang, Y., Lv, M., Wang, T., Sun, J., Wang, Y., Xia, M., Jiang, Y., Zhou, X., & Wan, J. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.112166 · Cited by 53
Eshraghi, R. S., Davies, C., Iyengar, R., Perez, L., Mittal, R., & Eshraghi, A. A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm10010027 · Cited by 58
“These bidirectional interactions occur via a complex integrated signaling pathway between the CNS, enteric nervous system (ENS), autonomic nervous system (ANS), and hypothalamic-pituitary-adrenal (HPA) axis [12].”
BackgroundMicrobes Tickling Your Tummy: the Importance of the Gut-Brain Axis in Parkinson’s Disease
Perez‐Pardo, P., Hartog, M., Garssen, J., & Kraneveld, A. D. (2017) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-017-0129-2 · Cited by 53
Montanari, M., Imbriani, P., Bonsi, P., Martella, G., & Peppe, A. (2023) · Biomedicines · doi:10.3390/biomedicines11061560 · Cited by 51
“The bidirectional communication between the gut and the brain implies a vital role for the gut microbiome through regulating host metabolism and immune and vascular systems [19].”
Wang, L., Wang, Z., Lan, Y., Tuo, Y., Ma, S., & Liu, X. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c03568 · Cited by 54
Cluny, N. L., Reimer, R. A., & Sharkey, K. A. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.01.004 · Cited by 51
Integrative Therapies in Anxiety Treatment with Special Emphasis on the Gut Microbiome.
Schnorr, S. L., & Bachner, H. A. (2016) · PubMed · Cited by 53
Blasco, G., Moreno‐Navarrete, J. M., Rivero, M., Pérez‐Brocal, V., Garre‐Olmo, J., Puig, J., Daunis‐i‐Estadella, P., Biarnés, C., Gich, J., Fernández‐Aranda, F., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00133 · Cited by 51
“Alterations in gut microbiom e could affect human brain health by producing systemic and/or CNS inflammation; stimula te dysfunctional responses of the adaptive immune system; exert neurotoxicity; and/or stimulate afferent neurons of the enteric nervous system [1].”
BackgroundFakhri, S., Yarmohammadi, A., Yarmohammadi, M., Farzaei, M. H., & Echeverría, J. (2021) · Marine Drugs · doi:10.3390/md19030165 · Cited by 52
“ANS synapses are the places that sense the microbial metabolites as the tools of communication of microbiota with each other [33].”
BackgroundThe chemistry of gut microbiome in health and diseases
Lau, A., Tan, L. T., Mutalib, N. A., Wong, S. H., Letchumanan, V., & Lee, L. (2021) · Progress In Microbes & Molecular Biology · doi:10.36877/pmmb.a0000175 · Cited by 55
“In recent years, there are increasing studies supporting this bi-directional relationship between the brain and the gut([215,216]).”
BackgroundLucarini, E., Pilato, V. D., Parisio, C., Micheli, L., Toti, A., Pacini, A., Bartolucci, G., Baldi, S., Niccolai, E., Amedei, A., et al. (2021) · Pain · doi:10.1097/j.pain.0000000000002438 · Cited by 55
“The brain, by the autonomic nervous system and the hypothalamic–pituitary–adrenal axis, influences intestinal functions and gut microbial composition.(77) On the other hand, microbiota alterations can influence brain structure and function either developmentally or in response to acute”
BackgroundXu, M., Zhou, E. Y., & Shi, H. (2025) · Cells · doi:10.3390/cells14050384 · Cited by 58
“Ultimately, these interactions help to regulate gut and CNS functions, including appetite and satiety, nutrient metabolism, energy homeostasis, immune responses, mood, and behavior [3,7,9,11,69,121].”
Healthy Gut, Healthy Brain: The Gut Microbiome in Neurodegenerative Disorders
Chandra, S., Alam, M. T., Dey, J., Sasidharan, B. C. P., Ray, U., Srivastava, A. K., Gandhi, S., & Tripathi, P. P. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200413091101 · Cited by 50
Animal Models in Biomedical Research
Maurer, K. J., & Quimby, F. W. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-409527-4.00034-1 · Cited by 51
Chen, H., Shen, J., Li, H., Zheng, X., Kang, D., Xu, Y., Chen, C., Guo, H., Xie, L. Y., Wang, G., et al. (2018) · Journal of Ginseng Research · doi:10.1016/j.jgr.2018.09.002 · Cited by 49
The gut microbiome: implications for neurogenesis and neurological diseases
Zhou, F., Liu, C., Yang, S., & Wang, L. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.315227 · Cited by 52
“…gut microbiota and the host brain; this communication occurs via the microbiota-gut-brain axis, which involves immunological, endocrine, neurological, and metabolic signaling pathways (Rhee et al., 2009; Cryan and Dinan, 2012; Janssen and Kersten, 2015; Mayer et al., 2015; Baizabal-Carvallo, 2021).”
Bamola, V. D., Dubey, D., Samanta, P., Kedia, S., Ahuja, V., Madempudi, R. S., Neelamraju, J., & Chaudhry, R. (2022) · Anaerobe · doi:10.1016/j.anaerobe.2022.102652 · Cited by 56
An Introductory Guide to Organizational Neuroscience
Murray, M. M., & Antonakis, J. (2018) · Organizational Research Methods · doi:10.1177/1094428118802621 · Cited by 51
Challenge and Prospect of Traditional Chinese Medicine in Depression Treatment
Zhang, Y., & Cheng, Y. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00190 · Cited by 51
Yan, R., Ho, C., & Zhang, X. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202000187 · Cited by 49
Past, Present, and Future of Gastrointestinal Microbiota Research in Cats
Lyu, Y., Su, C., Verbrugghe, A., de Wiele, T. V., Martinez-Caja, A. M., & Hesta, M. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01661 · Cited by 55
The intestinal microbiome of infants and the use of probiotics
Indrio, F., & Neu, J. (2011) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e3283444ccb · Cited by 48
“The brain can influence commensal organisms via changes in gastrointestinal motility, 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).(2) Enteric microbiota communication occurs via…”
The Controversial Role of Food Allergy in Infantile Colic: Evidence and Clinical Management
Nocerino, R., Pezzella, V., Cosenza, L., Amoroso, A., Scala, C. D., Amato, F., Iacono, G., & Canani, R. B. (2015) · Nutrients · doi:10.3390/nu7032015 · Cited by 49
Parvaneh, M., Karimi, G., Jamaluddin, R., Ng, M. H., Ibrahim, Z., & Ismaila, M. S. (2018) · Clinical Interventions in Aging · doi:10.2147/cia.s169223 · Cited by 48
“In this regard, beneficial microbes stimulate endocrine cells which are located in the gut and improve the immune system.(46) Since stem cells in the bone marrow generate T cell precursors, the immune system interacts with these pathways.”
Fuloria, S., Mehta, J., Talukdar, M. P., Sekar, M., Gan, S. H., Subramaniyan, V., Rani, N. N. I. M., Begum, M. Y., Chidambaram, K., Nordin, R. B., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.950913 · Cited by 57
“To date, it has been confirmed that there is a bi-directional link or connection between the intestine and the brain involving neurological, metabolic, hormonal and immunological signaling pathways where its alteration can bring altered behavior in these systems (Rhee et al., 2009).”
BackgroundPavlidou, E., Fasoulas, A., Mantzorou, M., & Giaginis, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415898 · Cited by 51
“The two-way connection that exists between the microbiota in the stomach and the organs throughout the body is mediated in healthy people by a few different pathways [7].”
BackgroundSaint-Martin, V., Guillory, V., Chollot, M., Fleurot, I., Kut, E., Roesch, F., Caballero, I., Helloin, E., Chambellon, É., Ferguson, B. J., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-06815-0 · Cited by 54
“Theperiphery,includingtheliver,adiposetissue, lungs,andbrain,isparticularlysensitivetoSCFAsandothermicrobial metabolites,leadingtothecoiningoftermssuchas “ gut-lungaxis ” and “ gut-brain axis ” 7,8 .”
The Link between Gut Dysbiosis Caused by a High-Fat Diet and Hearing Loss
Kociszewska, D., Chan, J., Thorne, P. R., & Vlajkovic, S. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413177 · Cited by 51
Implications of gut microbiota dysbiosis and metabolic changes in prion disease
Yang, D., Zhao, D., Shah, S. Z. A., Wu, W., Lai, M., Zhang, X., Li, J., Guan, Z., Zhao, H., Li, W., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104704 · Cited by 46
Potential of gut microbiome for detection of autism spectrum disorder
Wu, T., Wang, H., Lu, W., Zhai, Q., Zhang, Q., Yuan, W., Gu, Z., Zhao, J., Zhang, H., & Chen, W. (2020) · Microbial Pathogenesis · doi:10.1016/j.micpath.2020.104568 · Cited by 46
The Brain-Gut Axis: A Target for Treating Stress-Related Disorders
Scott, L. V., Clarke, G. A., & Dinan, T. G. (2013) · Modern trends in psychiatry · doi:10.1159/000343971 · Cited by 46
Manco, M. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00109 · Cited by 48
“The humans’ internal ecosystem (“human microbiome”) seems to intrude and modify significantly this bidirectional communication starting very early in the life so much to led some to suggest that the brain–gut axis may be more accurately termed “the brain–gut–microbiota axis” (Rhee et al., 2009).”
BackgroundGeorge, A. K., Behera, J., Homme, R. P., Tyagi, N., Tyagi, S. C., & Singh, M. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02357-2 · Cited by 44
Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma
D’Alessandro, G., Lauro, C., Quaglio, D., Ghirga, F., Botta, B., Trettel, F., & Limatola, C. (2021) · Cancers · doi:10.3390/cancers13112810 · Cited by 47
Alverdy, J. C., & Luo, J. N. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00322 · Cited by 47
“A complex molecular dialog is developing as these two living organisms interact, exchange signals, and behave as one multi-cellular system (Rhee et al., 2009).”
Cossu, G., Carta, M. G., Contu, F., Mela, Q., Demelia, L., Elli, L., & Dell’Osso, B. M. (2017) · International Review of Psychiatry · doi:10.1080/09540261.2017.1314952 · Cited by 46
Huang, L., Ma, Z., Ze, X., Zhao, X., Zhang, M., Lv, X., Zheng, Y., & Liu, H. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1189008 · Cited by 46
“…could damage the barrier function by downregulating expression of tight junction proteins, thus decreasing the intestinal mucosal barrier and blood-brain barrier, thus improving the harmful components accessed to periphery, thus increasing inflammation (Rhee et al., 2009; Maqsood and Stone, 2016).”
BackgroundResultHanai, A., Ishiguro, H., Sozu, T., Tsuda, M., Arai, H., Mitani, A., & Tsuboyama, T. (2015) · Breast Cancer Research and Treatment · doi:10.1007/s10549-015-3652-4 · Cited by 44
“study, increases in physical activity or SM skills may stimulate physical functioning, such as the volume of stool, reduce the occurrence of severe depressive symptoms, and promote emotional well-being [32, 36, 37].”
BackgroundFukuda, S., Miyauchi, T., Fujita, M., Oda, Y., Todani, M., Kawamura, Y., Kaneda, K., & Tsuruta, R. (2016) · Journal of Intensive Care · doi:10.1186/s40560-016-0156-1 · Cited by 44
“In terms of the relationship between central nervous and enteral nervous system, the brain–gut–microbiota axis has been a focus of numerous studies because of its potential functional roles [18–21, 29].”
Gut Microbiota and Neurologic Diseases and Injuries
Patterson, T. T., & Grandhi, R. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-2385-4_6 · Cited by 46
Bai, J., Bruner, D. W., Fedirko, V., Beitler, J. J., Zhou, C., Gu, J., Zhao, H., Lin, I., Chico, C. E., Higgins, K. A., et al. (2020) · Cancers · doi:10.3390/cancers12092531 · Cited by 44
“According to the microbiome–gut–brain axis model [12], the gut microbiome may regulate the development of the PNS cluster through neural, immune, metabolic, and hormonal pathways [13,14].”
BackgroundWang, F., Fei, M., Hu, W., Wang, X., Liu, S., Zeng, Y., Zhang, J., Lv, Y., Niu, J., Meng, X., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.821654 · Cited by 47
Petakh, P., Duve, K. V., Oksenych, V., Behzadi, P., & Kamyshnyi, O. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1394953 · Cited by 50
Vinke, P. C., Aidy, S. E., & van Dijk, G. (2017) · Frontiers in Nutrition · doi:10.3389/fnut.2017.00034 · Cited by 43
Witt, S. T., Bednarska, O., Keita, Å. V., Icenhour, A., Jones, M. P., Elsenbruch, S., Söderholm, J. D., Engström, M., Mayer, E. A., & Walter, S. (2018) · NeuroImage Clinical · doi:10.1016/j.nicl.2018.11.012 · Cited by 45
“…between the brain and the gut previously reported in preclinical studies are mediated by multiple communication channels, including spinal and vagal afferents, and the two branches of the autonomic nervous system (Cryan and Dinan, 2012; Mayer et al., 2006; Mayer et al., 2015b; Rhee et al., 2009).”
BackgroundSelf-citationPrebiotic oligosaccharides from dragon fruits alter gut motility in mice
Khuituan, P., K-da, S., Bannob, K., Hayeeawaema, F., Peerakietkhajorn, S., Tipbunjong, C., Wichienchot, S., & Charoenphandhu, N. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108821 · Cited by 45
Progress on traditional Chinese medicine in treatment of ischemic stroke via the gut-brain axis
Zhai, Z., Su, P., Ma, L.-Y., Yang, H., Wang, T., Fei, Z.-G., Zhang, Y., Wang, Y., Ma, K., Han, B.-B., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114056 · Cited by 44
Stress in the microbiome-immune crosstalk
Beurel, E. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2327409 · Cited by 48
“125,126 Although modulation of the microbiota affects both cognition and mood, 106,116,127–132 the mechanisms whereby the gut microbiota promotes depression remains to be fully understood.”
BackgroundNobutani, K., Sawada, D., Fujiwara, S., Kuwano, Y., Nishida, K., Nakayama, J., Kutsumi, H., Azuma, T., & Rokutan, K. (2016) · Journal of Applied Microbiology · doi:10.1111/jam.13329 · Cited by 42
“A bidirectional interaction between the intestinal microbiota and the host central nervous system (CNS) is frequently observed under stressful conditions (Rhee et al. 2009).”
BackgroundSzőke, H., Kovács, Z., Bókkon, I., Vagedes, J., Erdöfi-Szabó, A., Hegyi, G., Sterner, M.-G., Kiss, Á., & Kapócs, G. (2020) · Reviews in the Neurosciences · doi:10.1515/revneuro-2019-0095 · Cited by 44
Luo, M., Zhuang, X., Tian, Z., & Xiong, L. (2021) · BMC Gastroenterology · doi:10.1186/s12876-020-01577-5 · Cited by 45
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“Introduction In the human gastrointestinal tract, there are up to 1×10(12) bacterial cells per gram of colonic content, and gut microflora is constituted by 400-1,000 species of bacteria.(1,2) Balanced intestinal microflora plays a direct impact on maintaining the gut homeostasis such as regulating bowel motility, mod…”
BackgroundSelf-citationCastanedo-Vazquez, D., Bosque-Varela, P., Sainz-Pelayo, A., & Riancho, J. (2019) · Journal of Neurology · doi:10.1007/s00415-018-8919-3 · Cited by 41
Monocyte mobilisation, microbiota & mental illness
van de Wouw, M., Boehme, M., Dinan, T. G., & Cryan, J. F. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.07.019 · Cited by 41
Tomova, A., Šoltýs, K., Repiská, G., Pálková, L., Filcikova, D., Minárik, G., Turna, J., Prochotska, K., Babinská, K., & Ostatníková, D. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112745 · Cited by 46
Raval, U., Harary, J. M., Zeng, E., & Pasinetti, G. M. (2020) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2020.1775585 · Cited by 45
“Conversely, the brain communicates directly with the GM by releasing signaling molecules into the gut lumen and indirectly by altering gastric motility, secretion, and intestinal permeability [53].”
BackgroundKraeuter, A.-K., Phillips, R., & Sarnyai, Z. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00799 · Cited by 43
Mao, S., Huang, C.-P., Lan, H., Lau, H.-G., Chiang, C., & Chen, Y. (2022) · Journal of Dental Sciences · doi:10.1016/j.jds.2022.07.001 · Cited by 43
“The establishment of the gutebrain axis connected gastrointestinal microbiota with cognition decline, suggesting a possible association between bacteria and AD development.(18,19) Bacterial products such as LPS and short chain fatty acids (SCFA) can modulate the peripheral and central nervous systems and act as a pote…”
BackgroundZhu, X., Hu, J., Deng, S., Tan, Y., Qiu, C., Zhang, M., Ni, X., Lu, H., Wang, Z., Li, L., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.687757 · Cited by 40
Chronic Intestinal Inflammation Suppresses Brain Activity by Inducing Neuroinflammation in Mice
Mitchell, J., Kim, S. J., Howe, C. S., Lee, S., Her, J. Y., Patel, M., Kim, G., Lee, J., Im, E., & Rhee, S. H. (2021) · American Journal Of Pathology · doi:10.1016/j.ajpath.2021.09.006 · Cited by 42
Self-citationWegh, C. A. M., Benninga, M. A., & Tabbers, M. M. (2018) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001054 · Cited by 40
Patterson, T. T., Nicholson, S. E., Wallace, D. J., Hawryluk, G. W. J., & Grandhi, R. (2018) · Shock · doi:10.1097/shk.0000000000001278 · Cited by 42
“Through a variety of mechanisms, the gut microbes are able to regulate bowel motility, modulate intestinal pain, affect immune activity, and contribute to nutrient production and processing (13).”
BackgroundRedweik, G. A. J., Daniels, K. M., Severin, A. J., Lyte, M., & Mellata, M. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.03064 · Cited by 40
“Thus, increases in these IgA may decrease risks for APEC infection by interfering with APEC translocation into the bloodstream at mucosal surfaces like the lung via connections between the gut-lung axis (Samuelson et al., 2015).”
BackgroundZhang, T., Han, Y., Wang, J., Hou, D., Deng, H., Deng, Y. L., & Song, Z. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00176 · Cited by 38
Haimov, I., Magzal, F., Tamir, S., Lalzar, M., Asraf, K., Milman, U., Agmon, M., & Shochat, T. (2022) · Nature and Science of Sleep · doi:10.2147/nss.s377114 · Cited by 43
“Perturbation of these systems results in alterations in the stress response and overall behavior.(30) Findings have shown that gut microbiota modulates stressrelated mental illness, ie, depression and anxiety.”
BackgroundHomer, B., Judd, J., Dehcheshmeh, M. M., Ebrahimie, E., & Trott, D. J. (2023) · Animals · doi:10.3390/ani13091458 · Cited by 39
Yassin, L. K., Skrabulyte-Barbulescu, J., Alshamsi, S. H., Saeed, S., Alkuwaiti, S. H., Almazrouei, S., Alnuaimi, A., BaniYas, S., Aldhaheri, D., Alderei, M., et al. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1667448 · Cited by 48
Marco, M. L., Cunningham, M., Bischoff, S. C., Clarke, G. A., Delzenne, N. M., Lewis, J., Meisel, M., Merenstein, D. J., O’Toole, P. W., Staudacher, H. M., et al. (2026) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-026-01176-x · Cited by 50
Sellers, R. S., & Morton, D. G. (2013) · Toxicologic Pathology · doi:10.1177/0192623313505930 · Cited by 44
“Signaling from both the submuco- sal and the myenteric plexi are important in gut motility, although the myenteric plexi have a greater role in motility than the submucosal plexi, which have a greater role in colonic secretion and absorption (Kunze and Furness 1999; Nezami and Srinivasan 2010; Sarna and Shi 2006).”
BackgroundInfluential
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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