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
AI snapshot
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.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
72 Not checked yet · 40 Own interpretation · 1 No basis given
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 mechanisms that underlie the observed effects are poorly understood.”
§ Principles and clinical implications of the brain–gut–enteric microbiota axis > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“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
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Interestingly, 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As 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.
- 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.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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”
Background
Cited by
Sorted by citations
Items 701–800 of 999
Young at Gut—Turning Back the Clock with the Gut Microbiome
Narasimhan, H., Ren, C. C., Deshpande, S., & Sylvia, K. E. (2021) · Microorganisms · doi:10.3390/microorganisms9030555 · Cited by 17
“The crosstalk between the complex system consisting of the nervous system (central, autonomic, and enteric), the gut microbiota, and the hypothalamic pituitary adrenal (HPA) axis is regulated by neuro-immuno-metabolic-endocrine mediators [44].”
BackgroundCould the Gut Microbiota Serve as a Therapeutic Target in Ischemic Stroke?
Zhang, J., Tang, Q., & Zhu, L. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/1391384 · Cited by 17
“Stroke directly affects the composition of the gut microbiota, by either indirectly changing the intestinal microenvironment or generating a large number of molecular signals [32, 128].”
BackgroundZhang, Y., Cong, D.-Y., Liu, P., Zhi, X.-Y., Shi, C.-C., Zhao, J.-J., & Zhang, H.-S. (2021) · Medicine · doi:10.1097/md.0000000000025854 · Cited by 19
“A number of the studies have established that the signal regulation system of the gastrointestinal tract and the brain is the only system in the body jointly controlled by CNS, ENS, and ANS.”
BackgroundIrritable bowel syndrome: When food is a pain in the gut
Hussein, H., Remoortel, S. V., & Boeckxstaens, G. E. (2024) · Immunological Reviews · doi:10.1111/imr.13374 · Cited by 16
“47,48 However, whether dysbiosis acts as a causative element in disease development or is merely a consequence of changes in diet or bowel transit remains unclear.”
Raj, K., Singh, S., Chib, S., & Mallan, S. (2022) · Current Pharmaceutical Design · doi:10.2174/1381612828666221003112300 · Cited by 16
Liu, N., Liu, H.-Q., Zheng, J., Zhu, M., Wu, L., Pan, H., & He, X. (2023) · The Journal of Microbiology · doi:10.1007/s12275-023-00069-x · Cited by 16
“Recently, the interaction among brain, gut, and microbiota had been highlighted in the physiological and pathological process of neuronal system, which exhibit profound effects on neurological development and disorders (Lynch & Pedersen, 2016; Rhee et al., 2009).”
BackgroundJing, X., Hong, F., Xie, Y., Xie, Y., Shi, F., Wang, R., Wang, L., Chen, Z., & Liu, X. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115796 · Cited by 16
Faecal Microbiota Transplantation Alleviates Ferroptosis after Ischaemic Stroke
Wei, J., Wang, G., Lai, M., Zhang, Y., Li, F., Wang, Y., & Tan, Y. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.01.021 · Cited by 16
“Furthermore, the gut microbiota is associ-46 ated with the development of the CNS and brain function (Rhee et al., 2009; Claesson et al., 2012; Mu et al., 2016; Du et al., 2021).”
BackgroundLi, Y., Li, J., & Dai, C. (2024) · mBio · doi:10.1128/mbio.01533-24 · Cited by 23
“SCFAs are also important mediators of signal transmission between bacteria and host cells such as intestinal endocrine cells, immune cells, and neurons (5, 7, 8).”
BackgroundQuan, R., Decraecker, L., Appeltans, I., Cuende‐Estévez, M., Remoortel, S. V., Aguilera‐Lizarraga, J., Wang, Z., Hicks, G. A., Wykosky, J., McLean, P. G., et al. (2024) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000003042 · Cited by 16
A clinical primer of the role of gut microbiome in health and disease
Yang, A. L., & Kashyap, P. (2015) · Tropical Gastroenterology · doi:10.7869/tg.238 · Cited by 16
Zhu, Y., Xiong, Y., Gu, Y., Li, Q., & Liu, Y. (2020) · Medical Science Monitor · doi:10.12659/msm.926039 · Cited by 17
“BGPs are critical neurotransmitters, which not only modulate gastrointestinal function [50,51] but also participate in the interaction between gut microbiota and brain-gut axis [52].”
BackgroundHaddad, H. W., Mallepalli, N. R., Scheinuk, J. E., Bhargava, P., Cornett, E. M., Urits, I., & Kaye, A. D. (2021) · Pain and Therapy · doi:10.1007/s40122-021-00266-9 · Cited by 17
Microbiota links to neural dynamics supporting threat processing
Hall, C. V., Harrison, B. J., Iyer, K. K., Savage, H. S., Zakrzewski, M., Simms, L. A., Radford‐Smith, G. L., Moran, R., & Cocchi, L. (2021) · Human Brain Mapping · doi:10.1002/hbm.25682 · Cited by 14
Chen, B., Zhu, S., Du, L., He, H., Kim, J. J., & Dai, N. (2017) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2017.1342141 · Cited by 16
“Enteric microbiota can modulate gut motility and secretion, which in turn, likely influence the balance of enteric microbiota [30].”
BackgroundHypoxia: A cause of acute renal failure and alteration of gastrointestinal microbial ecology
Nandi, D., Samanta, A., Patra, A., Mandal, S., Roy, S., Das, K., & Kar, S. (2018) · Saudi Journal of Kidney Diseases and Transplantation · doi:10.4103/1319-2442.239653 · Cited by 16
Granata, L., Gildawie, K. R., Ismail, N., Brenhouse, H. C., & Kopec, A. M. (2022) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2022.101143 · Cited by 15
“The gut microbiome modulates central nervous system functioning through the gut-brain axis (Cryan and O’Mahony, 2011; Rhee et al., 2009).”
BackgroundKetogenic Diet and Gut Microbiota: Exploring New Perspectives on Cognition and Mood
Jiang, Y., Chen, Y., Chen, Y., Gong, X., Chen, Z., & Zhang, X. (2025) · Foods · doi:10.3390/foods14071215 · Cited by 15
“This axis involves the nervous, endocrine, and immune systems [11,12]. this pathway, the gut This axis involves the nervous, endocrine, and immune systems [11,12]. microbiota influences brain function, regulates neurotransmitter production Through this pathway, the gut microbiota in fl uences brain…”
Hajare, S., & Kulkarni, Y. A. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149975 · Cited by 18
Parois, S. P., Duttlinger, A. W., Richert, B. T., Lindemann, S. R., Johnson, J. S., & Marchant, J. N. (2020) · Frontiers in Veterinary Science · doi:10.3389/fvets.2020.00140 · Cited by 16
“We now know that the microbiome and the brain communicate bi-directionally via multiple suggested mechanisms, known collectively as the microbiome-gut-brain axis (24, 25).”
BackgroundSun, W., Dang, Y., Dai, L., Liu, C., Wang, J., Guo, Y., Fan, B., Kong, J., Zhou, B., Ma, X., et al. (2023) · Aquatic Toxicology · doi:10.1016/j.aquatox.2023.106585 · Cited by 15
Sen, P., Prandovszky, E., Honkanen, J. K., Chen, O., Yolken, R. H., & Suvisaari, J. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.10.024 · Cited by 15
Pediatric migraine is characterized by traits of ecological and metabolic dysbiosis and inflammation
Papetti, L., CHIERICO, F. D., Frattale, I., Toto, F., Scanu, M., Mortera, S. L., Rapisarda, F., Michele, M. D., Monte, G., Ursitti, F., et al. (2024) · The Journal of Headache and Pain · doi:10.1186/s10194-024-01871-7 · Cited by 14
“The bidirectional communication between brain and gut is commonly referred as microbiome-gut-brain (MGB) axis [55, 63].”
BackgroundJiang, J., Xie, H., Cao, S., Xu, X., Zhou, J., Liu, Q., Ding, C., & Liu, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1547365 · Cited by 17
Serrano-Contreras, J. I., García‐Pérez, I., Meléndez-Camargo, M. E., & Zepeda, L. G. (2016) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2016.01.044 · Cited by 15
Al-Orf, N., El-Ansary, A. K., Bjørklund, G., Moubayed, N., Bhat, R. S., & Bacha, A. G. B. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0284-5 · Cited by 15
Indrio, F., Dargenio, V. N., Giordano, P., & Francavilla, R. (2019) · Advances in experimental medicine and biology · doi:10.1007/5584_2018_315 · Cited by 15
Gut microbiome in neuropsychiatric disorders
Granados, D. M. M., Villasana‐Salazar, B., Coan, A. C., Rizzi, L., Balthazar, M. L. F., Godoi, A. B., do Canto, A. M., da Rosa, D. C., Silva, L. S., Tacla, R., et al. (2022) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x-anp-2021-0052 · Cited by 17
The relationship between primary headache and constipation in children and adolescents
Park, M., Choi, M.-G., & You, S. J. (2015) · Korean Journal of Pediatrics · doi:10.3345/kjp.2015.58.2.60 · Cited by 15
Pathogenesis and management of diabetic gastroparesis: An updated clinically oriented review
Uppaluri, S., Jain, M. A., Ali, H., Shingala, J., Amin, D., Ajwani, T., Fatima, I., Patel, N., Kaka, N., Sethi, Y., et al. (2024) · Diabetes & Metabolic Syndrome: Clinical Research & Reviews · doi:10.1016/j.dsx.2024.102994 · Cited by 14
Microbiota in anorexia nervosa: potential for treatment
Landini, L., Dadson, P., Gallo, F., Honka, M., & Cena, H. (2022) · Nutrition Research Reviews · doi:10.1017/s0954422422000130 · Cited by 16
The effect of fecal microbiota transplantation on stroke outcomes: A systematic review
Pasokh, A., Farzipour, M., Mahmoudi, J., & Sadigh‐Eteghad, S. (2022) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2022.106727 · Cited by 15
Linking Puberty and the Gut Microbiome to the Pathogenesis of Neurodegenerative Disorders
Esposito, P., & Ismail, N. (2022) · Microorganisms · doi:10.3390/microorganisms10112163 · Cited by 14
Reutov, V. P., & Sorokina, E. G. (2022) · BIOPHYSICS · doi:10.1134/s0006350922060197 · Cited by 14
Klimkaitė, L., Liveikis, T., Kaspute, G., Armalytė, J., & Aldonytė, R. (2023) · Future Microbiology · doi:10.2217/fmb-2022-0258 · Cited by 16
Fernandes, A. M., Calduch-Giner, J. À., Pereira, G. D. V., Gonçalves, A. T., Dias, J. P., Johansen, J., Silva, T. S., Naya-Català, F., Piazzon, M. C., Sitjà‐Bobadilla, A., et al. (2024) · Animals · doi:10.3390/ani14152166 · Cited by 14
“Another key actor in the regulation of lipid metabolism is the gut microbiota, as it can modulate a wide range of host physiological processes from intermediary metabolism to cognitive function [82–84].”
BackgroundSingh, I., Anand, S., Gowda, D. J., Kamath, A., & Singh, A. K. (2024) · Biogerontology · doi:10.1007/s10522-024-10128-4 · Cited by 15
“The efferent neural pathways, which are connected to the endogenous pathways responsible for pain modulation, are collectively referred to as the "emotional motor system" (Rhee et al. 2009).”
BackgroundThe gut microbiome and the brain
Rykalo, N. A., Riehl, L., & Kress, M. (2024) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0000000000000717 · Cited by 16
“1) by impacting the host’s carbohydrate, lipid, and energy homeostasis [2,3,16,24–33].”
Jiao, F., Zhou, L., & Wu, Z. (2024) · Neurological Sciences · doi:10.1007/s10072-024-07878-x · Cited by 13
Gut Microbiome and Autism: Recent Advances and Future Perspectives
Liu, J., Zhang, M., & Kong, X. (2016) · North American Journal of Medicine and Science · Cited by 14
Fecal microbiota in the female prairie vole (Microtus ochrogaster)
Curtis, J. T., Assefa, S., Francis, A., & Köhler, G. A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0190648 · Cited by 15
Effect of gut microbes on olfactory behavior of Drosophila melanogaster larva
Slankster-Schmierer, E., Lee, C., Hess, K. M., Odell, S. R., & Mathew, D. (2019) · BIOS · doi:10.1893/0005-3155-90.4.227 · Cited by 14
“A wealth of recent articles highlight the bidirectional communication between the gut microbiota and the brain (Aziz and Thompson, 1998; Bercik et al., 2012; Cryan and Dinan, 2012; Konturek et al., 2004; Mayer, 2011; O’Mahony et al., 2009; Rhee et al., 2009).”
BackgroundShi, J., Yin, Q., Zhang, L., Wu, Y. H., Yi, P., Guo, M., Li, H., Yuan, L., Wang, Z., Zhuang, P., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.898360 · Cited by 14
“Intestinal microbes regulate brain homeostasis through multiple pathways, among which intestinal barrierinflammation is one of the main pathways (Rogers et al., 2016).”
BackgroundFrom brain-body function to conscious interactions
Signorelli, C. M., Boïls, J. D., Tagliazucchi, E., Jarraya, B., & Deco, G. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104833 · Cited by 19
Creus-Cuadros, A., Tresserra‐Rimbau, A., Quifer‐Rada, P., Martínez‐González, M. Á., Corella, D., Salas‐Salvadó, J., Fitó, M., Estruch, R., Gómez‐Gracia, E., Lapetra, J., et al. (2016) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2016.11.003 · Cited by 14
Almansa, C., Agrawal, A. K., & Houghton, L. A. (2012) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.12.9 · Cited by 14
Chronic stress, gut microbiota, and immunity: interconnections and implications for health
Jia, H., Guo, X., Wei, Y., Can, C., He, N., Zhang, H., Yang, X., Wu, H., Liu, W., & Ma, D. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-025-05376-y · Cited by 14
“The microbiota-gut-brain axis has been postulated as recent studies have acknowledged the pivotal role of microbiota in brain-gut communication [207–210].”
Nous Sommes Tous des Bacteries: Implications for medicine, pharmacology and public health
Triggle, D. J. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.08.005 · Cited by 13
“Increasing evidence documents an important role of the gut microbiota in this axis [81,82].”
BackgroundLin, G., Li, S., Huang, J., Gao, D., & Lü, J. (2021) · Fish Physiology and Biochemistry · doi:10.1007/s10695-021-01011-x · Cited by 13
High cholesterol diet, oxysterols and their impact on the gut–brain axis
Poli, G., Iaia, N., Leoni, V., & Biasi, F. (2022) · Redox Experimental Medicine · doi:10.1530/rem-22-0003 · Cited by 16
Gernone, F., Uva, A., Silvestrino, M., Cavalera, M. A., & Zatelli, A. (2022) · Biology · doi:10.3390/biology11091290 · Cited by 13
Wang, R., Sun, Y., Wang, M., Li, H., Liu, S., & Liu, Z. (2023) · Phytotherapy Research · doi:10.1002/ptr.7947 · Cited by 14
“…and cytokines, rapidly increasing intestinal permeability, damaging the host's antibacterial function, destroying the intestinal barrier, promoting the displacement and transmission of symbiotic bacteria, and ultimately aggravating the outcome of a stroke (Rhee et al., 2009; Stanley et al., 2016).”
BackgroundVasilev, G., Miteva, D., Gulinac, M., Chervenkov, L., Kitanova, M., & Velikova, T. V. (2024) · Gastroenterology Insights · doi:10.3390/gastroent15030041 · Cited by 14
“However, it has been shown that exposure to environmental pollutants can lead to systemic consequences, including changes in brain functions and behavior [57–59].”
BackgroundBessette, C., Henry, G., Sekkal, S., Benoit, B., Bruno, J., Meugnier, E., Ferrier, L., Théodorou, V., Léonil, J., & Plaisancié, P. (2016) · Journal of Functional Foods · doi:10.1016/j.jff.2016.09.007 · Cited by 13
Traditional Chinese Medicine in Emergency Treatment Mechanism and Application
Yu, M., Michelena, T. M., Cai, F., Lou, X., Li, S., & Zhang, R. (2020) · Open Access Emergency Medicine · doi:10.2147/oaem.s244110 · Cited by 13
Brain Volume Loss, Astrocyte Reduction, and Inflammation in Anorexia Nervosa
Seitz, J., Trinh, S., Kogel, V., & Beyer, C. (2021) · Advances in neurobiology · doi:10.1007/978-3-030-77375-5_12 · Cited by 15
Progesterone: A Neuroprotective Steroid of the Intestine
Stegemann, L. N., Neufeld, P. M., Hecking, I., Vorgerd, M., Matschke, V., Stahlke, S., & Theiß, C. (2023) · Cells · doi:10.3390/cells12081206 · Cited by 12
“Still, a similar neuroprotective potential of progesterone in the CNS was postulated based on experimental animal models [58].”
BackgroundInfluentialVijayakumar, P., & Praveen, S. (2017) · Frontiers in Pediatrics · doi:10.3389/fped.2016.00136 · Cited by 13
“Psychological stressors have been reported to modulate infant gut microbiome (47).”
BackgroundSchauss, E., Horn, G., Ellmo, F. I., Reeves, T. J., Zettler, H. R., Bartelli, D., Cogdal, P., & West, S. L. (2019) · Journal of Mental Health Counseling · doi:10.17744/mehc.41.3.04 · Cited by 13
Saniotis, A., Grantham, J. P., Kumaratilake, J., & Henneberg, M. (2020) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2019.00101 · Cited by 14
“CNS and EGM Communication The ability for the EGM to communicate with the human brain via the gut-brain-enteric-microbiota-axis (GBEMA) in order to maintain symbiotic homeostasis is a crucial aspect of neurohormonal regulation and plays a pivotal role in human cognition (Rhee et al., 2009; Mayer, 2011; Carabotti et al…”
BackgroundDual real-time in vivo monitoring system of the brain-gut axis
Nishimura, Y., Fukuda, Y., Okonogi, T., Yoshikawa, S., Karasuyama, H., Osakabe, N., Ikegaya, Y., Sasaki, T., & Adachi, T. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.01.090 · Cited by 13
Fraga‐Silva, T. F. D. C., Mimura, L. A. N., de Oliveira, L. R. C., de Toledo, J. H. D. S., Borim, P. A., Zorzella-Pezavento, S. F. G., Alonso, D. P., Ribolla, P. E. M., de Oliveira, C. A. F., da Fonseca, D. M., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-79102-7 · Cited by 13
Li, C., Ye, F., Xu, C.-X., Chang, Q., Liu, X., & Pan, R. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.115349 · Cited by 13
The effect of microbiome composition on impulsive and violent behavior: A systematic review
Langmajerová, M., Roubalová, R., Šebela, A., & Vevera, J. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.114266 · Cited by 15
Intestinal crosstalk between bile acids and microbiota in irritable bowel syndrome
Deng, X., Xiao, L., Luo, M., Xie, P., & Xiong, L. (2023) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16159 · Cited by 16
Coker, J. (2023) · Faculty Reviews · doi:10.12703/r/12-27 · Cited by 12
“These interactions are well documented and have shown that the gut microbiome helps to maintain brain chemistry and cognition while the nervous system modulates the GI tract in multiple ways, thereby sustaining the gut microbiome 69,70 .”
BackgroundTang, C., Liu, H., Zou, H., Su, M., Yin, H., Sun, M., Zhao, Y., Guo, J., Lai, X., Xue, X., et al. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2023.11.029 · Cited by 12
Käver, L., Voelz, C., Specht, H. E., Thelen, A. C., Keller, L., Dahmen, B., Andreani, N. A., Tenbrock, K., Biemann, R., Borucki, K., et al. (2024) · Nutrients · doi:10.3390/nu16111596 · Cited by 12
“The connection between psychiatric disorders and the gastrointestinal tract is regulated by the gut–brain axis [38,86], which favours bidirectional communication between the central nervous system (brain and spinal cord) and the enteric nervous system, including gut bacteria and their metabolites…”
BackgroundThakur, P., Baraskar, K., Shrivastava, V. K., & Medhi, B. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149176 · Cited by 12
Liu, S., Liu, J., Xiang, J., Yan, R., Li, S., Fan, Q., Lu, L., Wu, J., Xue, Y., Fu, T., et al. (2024) · American Journal Of Pathology · doi:10.1016/j.ajpath.2024.11.010 · Cited by 13
Antibiotics-induced dysbiosis impacts dendritic morphology of adult mouse cortical interneurons
Nakhal, M. M., Mydeen, A. B., Yassin, L. K., Almazrouei, R., Alkamali, R., Alsulaimi, M., Elsaleh, R. I., BaniYas, S., Houqani, S. A., Al-Marzooq, F. I., et al. (2025) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2025.1557961 · Cited by 12
“The concept of the MGBA emerged from extensive research conducted over the past three decades, which has clearly demonstrated a direct connection between the gut and the brain (Rhee et al., 2009; Cryan and O’Mahony, 2011; De Palma et al., 2014; Cryan et al., 2019; Nakhal et al., 2024).”
The Role of Probiotics in Modulating the Gut Microbiome in Alzheimer’s Disease: A Review
Dong, Y., Wu, X., Zhang, Y., Hu, A., Zhou, Q., Yue, X., Liu, Z., & Li, M. (2025) · Foods · doi:10.3390/foods14091531 · Cited by 15
“Intestinal products, such as microbiome-derived metabolites, hormones, and neuroactive molecules, can regulate the ENS, CNS, neuroendocrine system, and immune system [81,82].”
Kim, Y., & Pritts, T. A. (2017) · Springer eBooks · doi:10.1007/978-3-319-48687-1_5 · Cited by 12
Nishida, K., Sawada, D., Yasui, T., Kuwano, Y., & Rokutan, K. (2021) · Journal of Functional Foods · doi:10.1016/j.jff.2021.104426 · Cited by 12
Kim, S., Zhang, W., Pak, V. M., Aqua, J. K., Hertzberg, V., Spahr, C. M., Slavich, G. M., & Bai, J. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-047281 · Cited by 12
Neuropathy in COVID-19 associated with dysbiosis-related inflammation
Aktaş, B., & Aslım, B. (2021) · TURKISH JOURNAL OF BIOLOGY · doi:10.3906/biy-2105-53 · Cited by 12
“…in the gut microbial composition, increased intestinal permeability and activated immune response may lead to systemic inflammation and impact the blood-brain barrier, and eventually induce neural injury and neurodegeneration with neuroinflammation (Rhee et al., 2009; Heiss and Olofsson 2019).”
BackgroundInfluentialRichardson, B. N., Noh, H. I., Webster, C., Zhang, W., Kim, S., Yang, I. H., & Bai, J. (2023) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2022.0182 · Cited by 12
Ikuta, K., Joho, D., Kakeyama, M., & Matsumoto, M. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1164809 · Cited by 13
“Recent studies have revealed that intestinal microbiota affects the gut-brain axis, which influences bidirectional signaling between the gastrointestinal tract and the brain via the nervous system and neurotransmitters, a concept termed as the “microbiota-gutbrain axis” (16).”
BackgroundEffects of interactions between intestinal microbiota and intestinal macrophages on health.
Nakata, K., Yamamoto, M., Inagawa, H., & Soma, G. (2013) · PubMed · Cited by 12
Psychobiotics; A Promise for Neurodevelopmental Therapy
Daliri, E. B., & Oh, D. (2016) · Journal of Probiotics & Health · doi:10.4172/2329-8901.1000146 · Cited by 12
“Many CNS disorders are associated with dysbiosis in the gut resulting in gastrointestinal disturbance [22].”
BackgroundStressing Out about Cancer Immunotherapy.
He, X.-Y., Ng, D., Aelst, L. V., & Egeblad, M. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.013 · Cited by 12
Mulak, A. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2020.1701437 · Cited by 13
Banerjee, A., Pradhan, L. K., Sahoo, P. K., Jena, K. K., Chauhan, N. R., Chauhan, S., & Das, S. K. (2021) · Archives of Microbiology · doi:10.1007/s00203-021-02276-9 · Cited by 13
Gastrointestinal motility disorders in patients with anorexia nervosa – a review of the literature
Weterle-Smolińska, K. A., Banasiuk, M., Dziekiewicz, M., Ciastoń, M., Jagielska, G., & Banaszkiewicz, A. (2015) · Psychiatria Polska · doi:10.12740/pp/35482 · Cited by 12
Clostridioides difficile and neurological disorders: new perspectives
Biazzo, M., Allegra, M., & Deidda, G. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.946601 · Cited by 11
“…01 frontiersin.org (SCFAs), and the primary and secondary bile acid (BAs) pathways; (ii) the vagus nerve acts as communication pathway (Rhee et al., 2009; Grenham et al., 2011); (iii) moreover, bacteria themselves are able to synthesize and then regulate the level of many…”
BackgroundThe link between gut microbiota and multiple sclerosis from the perspective of barrier function
Ren, J., Niu, Z., Wang, J., Guo, J., Hao, H.-J., Gao, F., Liu, R., & Wang, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1652796 · Cited by 13
The Microbiome–Neurodegeneration Interface: Mechanisms, Evidence, and Future Directions
Böckels, L., Alexa, D., Antal, D. C., Gațcan, C., Alecu, C., Kacani, K., Cretu, R. A., Piseru, E.-A., Bîlcu, R. V., & Cuciureanu, D. I. (2026) · Cells · doi:10.3390/cells15020135 · Cited by 13
Lu, G., Zhang, S., Wang, R., Zhang, Z., Wang, W., Wen, Q., Zhang, F., & Li, P. (2023) · Nutrients · doi:10.3390/nu15173704 · Cited by 11
Periodontal disease and risk of Alzheimer's disease: A two‐sample Mendelian randomization
Hu, C., Li, H., Huang, L., Wang, R., Wang, Z., Ma, R., Chang, B., Li, S., Li, H., & Li, G. (2024) · Brain and Behavior · doi:10.1002/brb3.3486 · Cited by 12
“The gut-brain axis has revealed an association between the gut microbiota and cognitive decline, suggesting a possible involvement of bacteria in AD pathogenesis (Lyte et al., 2006; Rhee et al., 2009).”
BackgroundSex differences in the performance of cognitive tasks in a murine model of metabolic syndrome
Espinosa‐García, C., Fuentes‐Venado, C. E., Guerra‐Araiza, C., Segura-Uribe, J. J., Chávez‐Gutiérrez, E., Farfán‐García, E. D., Estrada-Cruz, N. A., & Pinto‐Almazán, R. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14751 · Cited by 10
“Some mechanisms proposed are neuroinflammation caused by activation of pro-inflammatory milieu, changes on the concentration of neurotransmitters and short-chain fatty acids and overproduction of glucocorticoids in the gut-brain axis (Agustíet al., 2018; Rhee et al., 2009).”
BackgroundMarchi, F. D., Collo, A., Scognamiglio, A., Cavaletto, M., Cionci, N. B., Biroli, G., Gioia, D. D., Riso, S., & Mazzini, L. (2021) · Nutrition · doi:10.1016/j.nut.2021.111525 · Cited by 11
Bai, X., Batallé, G., Balboni, G., & Pol, O. (2022) · Antioxidants · doi:10.3390/antiox11071321 · Cited by 11
Watanabe, T., Hayashi, K., Takara, T., Teratani, T., Kitayama, J., & Kawahara, T. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19158936 · Cited by 11
“immune, endocrine, and neural pathways [9].”
Szewczyk, A., Andres‐Mach, M., Zagaja, M. P., Kaczmarczyk‐Ziemba, A., Maj, M., & Szala‐Rycaj, J. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45030168 · Cited by 13
Gastrointestinal Manifestations of Pediatric Autonomic Disorders
Chelimsky, G. G., & Chelimsky, T. C. (2013) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2013.01.002 · Cited by 11
“Norepinephrine is known to induce expression of virulent Pseudomonas aeruginosa, which can result in sepsis.(11) Norepinephrine also drastically increases the growth of enteric bacteria in vitro, through both direct and indirect effects.”
BackgroundSu, W., Lu, F., Zhang, X., Li, G., Chen, W., Ma, T., Gao, S., Lou, J., Bai, X., & Liang, T. (2017) · Medicine · doi:10.1097/md.0000000000008206 · Cited by 11
Influence of Gut Microbiota on Behavior and Its Disturbances
Ignatova, V. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.85317 · Cited by 13
An overview of addiction to sugar
Onaolapo, A. Y., Onaolapo, O. J., & Olowe, O. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816918-6.00009-3 · Cited by 13
Mayer, E. A., & Brunnhuber, S. (2012) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52002-9.00036-x · Cited by 11
Self-citationSuccessful dietary treatment of aggression and behavioral changes in a dog
Suñol, A., Pérez‐Accino, J., Kelley, M., Rossi, G., & Schmitz, S. S. (2020) · Journal of Veterinary Behavior · doi:10.1016/j.jveb.2020.04.009 · Cited by 11
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 ›
Are you an author, or do you see a problem with this page? Request a review
