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.
- 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.
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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 201–300 of 999
Wiley, N., Dinan, T. G., Ross, R. P., Stanton, C., Clarke, G. A., & Cryan, J. F. (2017) · Journal of Animal Science · doi:10.2527/jas.2016.1256 · Cited by 190
Impact of Microbial Metabolites on Microbiota–Gut–Brain Axis in Inflammatory Bowel Disease
Banfi, D., Moro, E., Bosi, A., Bistoletti, M., Cerantola, S., Crema, F., Maggi, F., Giron, M. C., Giaroni, C., & Baj, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041623 · Cited by 160
Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases
Biazzo, M., & Deidda, G. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11144119 · Cited by 172
Impact of Environmental Pollutants on Gut Microbiome and Mental Health via the Gut–Brain Axis
Singh, S., Sharma, P., Pal, N., Kumawat, M., Shubham, S., Sarma, D. K., Tiwari, R. R., Kumar, M., & Nagpal, R. (2022) · Microorganisms · doi:10.3390/microorganisms10071457 · Cited by 161
“Exposure to environmental pollutants has been demonstrated to target both the host and the resident gut microbiota, whose disturbance could have systemic repercussions including alterations in the functioning of CNS through the MGBA [21,45,46].”
BackgroundInfluentialProbiotics for Parkinson’s Disease
Gazerani, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174121 · Cited by 156
Hydroxycinnamic acids and human health: recent advances
Coman, V., & Vodnar, D. C. (2019) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.10010 · Cited by 158
Functional gastrointestinal disorders and gut-brain axis: What does the future hold?
Mukhtar, K., Nawaz, H., & Abid, S. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i5.552 · Cited by 157
Yan, X., Liu, X.-Y., Zhang, D., Zhang, Y., Li, Z., Liu, X., Wu, F., & Chen, G. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00760-2 · Cited by 151
Chen, S., Wang, J., Dandan, P., Li, G., Chen, J., & Gu, X. (2018) · Scientific Reports · doi:10.1038/s41598-018-32886-1 · Cited by 158
Sun, J., Wang, F., Ling, Z., Yu, X., Chen, W., Li, H., Jin, J., Pang, M., Zhang, H., Yu, J., et al. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.042 · Cited by 146
Microbiota‐gut‐brain axis as a regulator of reward processes
García‐Cabrerizo, R., Carbia, C., O’Riordan, K. J., Schellekens, H., & Cryan, J. F. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15284 · Cited by 150
“The microbiota-gut-brain-axis is a bidirectional pathway throughout which the brain regulates the activity of the gut and vice versa and is critical for the homeostasis of the host system (Rhee et al., 2009; Collins et al., 2012; Cryan et al. 2019) (Figure 1).”
BackgroundA potential role for the gut microbiome in substance use disorders
Meckel, K. R., & Kiraly, D. D. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05232-0 · Cited by 146
“Furthermore, opioids directly act on enteric neurons to slow colonic transit, which can in turn alter the gut microbiome due to changes in gut motility (Rhee et al. 2009; Smith et al. 2012; Zhu et al. 2014; Meng et al. 2015b; Parthasarathy et al. 2016).”
Influence of the microbiota-gut-brain axis on behavior and welfare in farm animals: A review
Kraïmi, N., Dawkins, M. S., Gebhardt‐Henrich, S. G., Velge, P., Rychlı́k, I., Volf, J., Créach, P., Smith, A. L., Colles, F. M., & Leterrier, C. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112658 · Cited by 161
The clinical evidence for postbiotics as microbial therapeutics
Mosca, A., y Abreu, A. T. A., Gwee, K., Ianiro, G., Tack, J. F., Nguyễn, T. V. H., & Hill, C. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2117508 · Cited by 156
Human Gut Microbiota: Toward an Ecology of Disease
Selber‐Hnatiw, S., Rukundo, B., Ahmadi, M., Akoubi, H., Al-Bizri, H., Aliu, A. F., Ambeaghen, T. U., Avetisyan, L., Bahar, I., Baird, A., et al. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01265 · Cited by 151
“…and le Roux, 2013; Avau et al., 2015; Avau andDepoortere, 2015; Murtaza et al., 2017), affect the vagus nerve which controls the gut-brain axis (Rhee et al., 2009; Bercik et al., 2012; Collins et al., 2012; Vaughn et al., 2017) and influence the release of toxins and neuro-transmitters (Kollai…”
BackgroundSun, J., Liu, S., Ling, Z., Wang, F., Ling, Y., Gong, T., Fang, N., Ye, S., Si, J., & Liu, J. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b07313 · Cited by 148
Gut Microbiota: A Perspective for Psychiatrists
Rea, K., Dinan, T. G., & Cryan, J. F. (2019) · Neuropsychobiology · doi:10.1159/000504495 · Cited by 146
Role of the Gut Microbiome in Autism Spectrum Disorders
Pulikkan, J., Mazumder, A., & Grace, T. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-05542-4_13 · Cited by 142
Microbes and the mind: emerging hallmarks of the gut microbiota-brain axis
Bauer, K. C., Huus, K. E., & Finlay, B. B. (2016) · Cellular Microbiology · doi:10.1111/cmi.12585 · Cited by 151
“…of microorganisms, collectively termed the gut microbiota, reside throughout the mammalian gastrointestinal (GI) tract, extending host digestive (Turnbaugh et al., 2007), metabolic (Nicholson et al., 2012), immune (Round and Mazmanian, 2009) and neural function (Sampson and Mazmanian, 2015).”
BackgroundCharacterization of Microbiota in Children with Chronic Functional Constipation
de Meij, T. G. J., de Groot, E. F. J., Eck, A., Budding, A. E., Kneepkens, C. M. F., Benninga, M. A., Bodegraven, A. A. V., & Savelkoul, P. H. M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0164731 · Cited by 141
Aging of the mammalian gastrointestinal tract: a complex organ system
Saffrey, M. J. (2013) · AGE · doi:10.1007/s11357-013-9603-2 · Cited by 141
“recently, the microbiota have been realised to impact upon these processes; the brain–gut–enteric microbiota axis is currently an area of intense research (Cryan and O'Mahony 2011; Forsythe and Kunze 2013; Rhee et al. 2009).”
BackgroundInfluentialSánchez, M., Darimont, C., Panahi, S., Drapeau, V., Marette, A., Taylor, V. H., Doré, J., & Tremblay, A. (2017) · Nutrients · doi:10.3390/nu9030284 · Cited by 138
Wei, L., Wen, X.-S., & Xian, C. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179474 · Cited by 137
“Gut-brain axis is the connection which exists between the central nervous system and the alimentary tract, in which the microbiota exerts a profound effect on the central nervous system, affecting behavioral, emotional and cognitive domains [80], potentially through the possible mechanisms as follows: (1) Short-chain…”
BackgroundPost-stroke remodeling processes in animal models and humans
Cirillo, C., Brihmat, N., Castel-Lacanal, E., Friec, A. L., Barbieux‐Guillot, M., Raposo, N., Pariente, J., Viguier, A., Simonetta‐Moreau, M., Albucher, J., et al. (2019) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x19882788 · Cited by 144
Liu, S., Guo, R., Liu, F., Yuan, Q., Yu, Y., & Ren, F. (2020) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s243551 · Cited by 130
Obesity-related cognitive impairment: The role of endothelial dysfunction
Buie, J. N. J., Watson, L. S., Smith, C. J., & Sims‐Robinson, C. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104580 · Cited by 138
Psychobiotics and the gut–brain axis: in the pursuit of happiness
Foster, J. A., & Zhou, L. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s61997 · Cited by 141
“brain in the modulation of human health is at the forefront of research examining the microbiome–gut–brain axis.(12,13,44,45)”
The microbiota and autoimmunity: Their role in thyroid autoimmune diseases
Köhling, H.-L., Plummer, S. F., Marchesi, J. R., Davidge, K. S., & Ludgate, M. (2017) · Clinical Immunology · doi:10.1016/j.clim.2017.07.001 · Cited by 139
Sanmiguel, C. P., Jacobs, J. P., Gupta, A., Ju, T., Stains, J., Coveleskie, K., Lagishetty, V., Balioukova, A., Chen, Y., Dutson, E., et al. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000494 · Cited by 133
Self-citationOrgan‐on‐a‐Chip Technology for Reproducing Multiorgan Physiology
Lee, S. H., & Sung, J. H. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700419 · Cited by 130
Changes in Gut Microbiota and Multiple Sclerosis: A Systematic Review
Ordoñez-Rodriguez, A., Román, P., Rueda‐Ruzafa, L., Campos-Ríos, A., & Cardona, D. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20054624 · Cited by 144
Gut Dysbiosis and Neurobehavioral Alterations in Rats Exposed to Silver Nanoparticles
Javurek, A. B., Suresh, D., Spollen, W. G., Hart, M. L., Hansen, S. A., Ellersieck, M. R., Bivens, N. J., Givan, S. A., Upendran, A., Kannan, R., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-02880-0 · Cited by 133
The Gut-Brain Axis in Neurodegenerative Diseases and Relevance of the Canine Model: A Review
Ambrosini, Y. M., Borcherding, D. C., Kanthasamy, A. G., Kim, H. J., Willette, A. A., Jergens, A. E., Allenspach, K., & Mochel, J. P. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00130 · Cited by 130
McKean, J., Naug, H., Nikbakht, E., Amiet, B., & Colson, N. (2017) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2016.0023 · Cited by 125
Age-related changes in intestinal immunity and the microbiome
Walrath, T., Dyamenahalli, K. U., Hulsebus, H. J., McCullough, R. L., Idrovo, J., Boe, D. M., McMahan, R. H., & Kovacs, E. J. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ri0620-405rr · Cited by 129
van de Wouw, M., Walsh, A. M., Crispie, F., van Leuven, L., Lyte, J. M., Boehme, M., Clarke, G., Dinan, T. G., Cotter, P. D., & Cryan, J. F. (2020) · Microbiome · doi:10.1186/s40168-020-00846-5 · Cited by 123
Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders
Israelyan, N., & Margolis, K. G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.020 · Cited by 122
Dysbiosis of the intestinal microbiota in neurocritically ill patients and the risk for death
Xu, R., Tan, C., Zhu, J., Zeng, X., Gao, X., Wu, Q., Chen, Q., Wang, H., Zhou, H., He, Y., et al. (2019) · Critical Care · doi:10.1186/s13054-019-2488-4 · Cited by 123
“The use of antibiotics [38], vasoactive agents, artificial nutrition, proton pump inhibitors, analgesics or sedative agents that impair intestinal motility [39] may affect the gut microbiota.”
BackgroundMutual Interactions among Exercise, Sport Supplements and Microbiota
Zeppa, S. D., Agostini, D., Gervasi, M., Annibalini, G., Amatori, S., Ferrini, F., Sisti, D., Piccoli, G., Barbieri, E., Sestili, P., et al. (2019) · Nutrients · doi:10.3390/nu12010017 · Cited by 128
“The gut itself produces hormones such as gamma aminobutyric acid and neuropeptide Y [119], and microbiota are able to secrete molecules such as SCFAs and tryptophan [120,121] which can, in turn, modulate inhibitory and excitatory neurotransmitters and neurotransmitter-like molecules [122].”
BackgroundEffects of Polyphenols on Brain Ageing and Alzheimer’s Disease: Focus on Mitochondria
Schaffer, S., Asseburg, H., Kuntz, S., Muller, W. E., & Eckert, G. P. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8282-9 · Cited by 124
Cellular changes in the enteric nervous system during ageing
Saffrey, M. J. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.03.015 · Cited by 124
The maternal gut microbiome during pregnancy and offspring allergy and asthma
Gao, Y., Nanan, R. K. H., Macia, L., Tan, J., Sominsky, L., Quinn, T. P., O’Hely, M., Ponsonby, A., Tang, M. L. K., Collier, F., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.07.011 · Cited by 129
“(68-70) Stress-induced release of glucocorticoids has 125 been suggested to mediate these effects,(71) but the impact of psychological stress and anxiety 126 on the maternal gut microbiome may also be relevant (12, 72-74).”
BackgroundBacteriophages as potential new mammalian pathogens
Tetz, G. V., Ruggles, K. V., Zhou, H., Heguy, A., Tsirigos, A., & Tetz, V. (2017) · Scientific Reports · doi:10.1038/s41598-017-07278-6 · Cited by 121
Victor, T. A., Khalsa, S. S., Simmons, W. K., Feinstein, J. S., Savitz, J. B., Aupperle, R. L., Yeh, H., Bodurka, J., & Paulus, M. P. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-016620 · Cited by 116
Korterink, J. J., Ockeloen, L., Benninga, M. A., Tabbers, M. M., Hilbink, M., & Deckers‐Kocken, J. M. (2014) · Acta Paediatrica · doi:10.1111/apa.12513 · Cited by 115
Implications of Diet and The Gut Microbiome in Neuroinflammatory and Neurodegenerative Diseases
Hirschberg, S., Gisevius, B., Duscha, A., & Haghikia, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20123109 · Cited by 120
The Mycobiome: A Neglected Component in the Microbiota-Gut-Brain Axis
Enaud, R., Vandenborght, L., Coron, N., Bazin, T., Prével, R., Schaeverbeke, T., Berger, P., Fayon, M. J., Lamireau, T., & Delhaès, L. (2018) · Microorganisms · doi:10.3390/microorganisms6010022 · Cited by 122
“However, the concept of “microbiome-gut-brain axis (-GBA)” has emerged very recently as a bidirectional communication system in which the digestive microbial flora, also known as the gut microbiome, play a key role [1].”
BackgroundZhao, L., Xiong, Q., Stary, C. M., Mahgoub, O. K., Ye, Y., Gu, L., Xiong, X., & Zhu, S. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1382-3 · Cited by 113
Chen, L., Hu, C., Lai, N. L.-S., Zhang, W., Hua, J., Lam, P. K. S., Lam, J. C. W., & Zhou, B. (2018) · Environmental Pollution · doi:10.1016/j.envpol.2018.04.062 · Cited by 114
Zhu, C. S., Grandhi, R., Patterson, T. F., & Nicholson, S. E. (2018) · Brain Sciences · doi:10.3390/brainsci8060113 · Cited by 112
He, Y., Kosciolek, T., Tang, J., Zhou, Y., Li, Z., Ma, X., Zhu, Q., Yuan, N., Yuan, L., Li, C., et al. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.05.011 · Cited by 123
“The concept of the microbiota-gut-brain axis was proposed nearly a decade ago [8].”
BackgroundTabrizi, M. A., Baraldi, P. G., Borea, P. A., & Varani, K. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00411 · Cited by 111
Current level of consensus on probiotic science-Report of an expert meeting-London, 23 November 2009
Rowland, I. R., Capurso, L., Collins, K., Cummings, J., Delzenne, N., Goulet, O., Guarner, F., Marteau, P., & Meier, R. (2010) · Gut Microbes · doi:10.4161/gmic.1.6.13610 · Cited by 109
The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke
Winek, K., Dirnagl, U., & Meisel, A. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0475-x · Cited by 108
Bistoletti, M., Caputi, V., Baranzini, N., Marchesi, N., Filpa, V., Marsilio, I., Cerantola, S., Terova, G., Baj, A., Grimaldi, A., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0212856 · Cited by 109
Correlations of Host Genetics and Gut Microbiome Composition
Dąbrowska, K., & Witkiewicz, W. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01357 · Cited by 113
“CNS may induce signals for neurons, immune cells and others secretory cells in the gut that release a variety of signaling molecules as well as anti-microbial peptides (AMPs) and modify composition of gut microbiota (Rhee et al., 2009; Cryan and Dinan, 2012; Wang and Kasper, 2014).”
BackgroundQuantifying your body: A how‐to guide from a systems biology perspective
Smarr, L. L. (2012) · Biotechnology Journal · doi:10.1002/biot.201100495 · Cited by 111
“Stress can even alter your gut microbial ecology through the brain-gut-enteric microbiota axis [19].”
BackgroundThe Brain-Gut Axis in Health and Disease
Omran, Y. A., & Aziz, Q. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0897-4_6 · Cited by 109
Childhood functional abdominal pain: mechanisms and management
Korterink, J., Devanarayana, N. M., Rajindrajith, S., Vlieger, A. M., & Benninga, M. A. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.21 · Cited by 106
From the intestinal flora to the microbiome
Domingo, J. J. S., & Sánchez, C. S. (2017) · Revista Española de Enfermedades Digestivas · doi:10.17235/reed.2017.4947/2017 · Cited by 117
Agostini, S., Goubern, M., Tondereau, V., Salvador–Cartier, C., Bézirard, V., Lévèque, M., Keränen, H., Théodorou, V., Bourdu-Naturel, S., Goupil-Feuillerat, N., et al. (2012) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01865.x · Cited by 106
Singh, R., Zogg, H., Ghoshal, U. C., & Ro, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.808195 · Cited by 112
Chen, L., Lam, J. C. W., Tang, L., Hu, C., Liu, M., Lam, P. K. S., & Zhou, B. (2020) · Environmental Science & Technology · doi:10.1021/acs.est.0c02345 · Cited by 100
Du, D., Tang, W., Zhou, C., Sun, X., Wei, Z., Zhong, J., & Huang, Z. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5816837 · Cited by 105
Sansores‐España, L. D., Melgar‐Rodríguez, S., Sagredo-Olivares, K., Cafferata, E. A., Martínez-Aguilar, V. M., Vernal, R., Paula-Lima, A. C., & Díaz‐Zúñiga, J. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.781582 · Cited by 110
“Commensal bacteria interact with enterocytes through the α2-receptor and can either increase or decrease the ability to eliminate pathogenic bacteria in the intestinal lumen (Rhee et al., 2009).”
BackgroundInfluentialEffect of Yoga in the Therapy of Irritable Bowel Syndrome: A Systematic Review
Schumann, D., Anheyer, D., Lauche, R., Dobos, G. J., Langhorst, J., & Cramer, H. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2016.04.026 · Cited by 108
Diet and host–microbial crosstalk in postnatal intestinal immune homeostasis
Jain, N., & Walker, W. A. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2014.153 · Cited by 108
Chen, L., Zhang, W., Hua, J., Hu, C., Lai, N. L.-S., Qian, P., Lam, P. K. S., Lam, J. C. W., & Zhou, B. (2018) · Environmental Science & Technology · doi:10.1021/acs.est.7b06322 · Cited by 107
Rouzé, R., Moné, A., Delbac, F., Belzunces, L., & Blot, N. (2019) · Microbes and Environments · doi:10.1264/jsme2.me18169 · Cited by 110
“Thus, besides local effects on the gut, insecticides exert pleiotropic effects that may, in turn, affect the gut and its microbiota, which is considered to be connected to the nervous system in mammals (69).”
Oxidative Stress at the Crossroads of Aging, Stroke and Depression
Shao, A., Lin, D., Wang, L., Tu, S., Lenahan, C., & Zhang, J. (2020) · Aging and Disease · doi:10.14336/ad.2020.0225 · Cited by 101
“Moreover, vagal afferent innervation of the enterochromaffin cells provides direct signaling to the neuronal circuits, leading to changes of the immuneresponse and other homeostatic functions [108].”
BackgroundBrain Autoimmunity and Intestinal Microbiota: 100 Trillion Game Changers
Wekerle, H. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.03.008 · Cited by 104
Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications
Battaglini, D., Pimentel‐Coelho, P. M., Robba, C., dos Santos, C. C., Cruz, F. F., Pelosi, P. P., & Rocco, P. R. M. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00598 · Cited by 100
“These include serotonin, gamma-amino butyric acid (GABA), catecholamines (12), cholecystokinin, glucagon-like peptide-1, and neuropeptide Y (7).”
BackgroundGender Differences in Stress‐ and Burnout‐Related Factors of University Professors
Redondo-Flórez, L., Tornero-Aguilera, J. F., Ramos‐Campo, D. J., & Clemente‐Suárez, V. J. (2020) · BioMed Research International · doi:10.1155/2020/6687358 · Cited by 136
The Impact of Microbiota on the Gut–Brain Axis: Examining the Complex Interplay and Implications
Chaudhry, T. S., Senapati, S. G., Gadam, S., Mannam, H. P. S. S., Voruganti, H. V., Abbasi, Z., Abhinav, T., Challa, A. B., Pallipamu, N., Bheemisetty, N., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12165231 · Cited by 111
From the Bottom-Up: Chemotherapy and Gut-Brain Axis Dysregulation
Bajic, J. E., Johnston, I. N., Howarth, G. S., & Hutchinson, M. R. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00104 · Cited by 100
“Recent advances in our understanding of the impact the microbiota has on the gut-brain axis has led to common use of the term microbiota-gut-brain axis (Rhee et al., 2009; De Palma et al., 2014).”
BackgroundNeufeld, K. M., O’Mahony, S. M., Hoban, A. E., Waworuntu, R. V., Berg, B. M., Dinan, T. G., & Cryan, J. F. (2017) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1397875 · Cited by 98
Sun, Q., Cheng, L., Zeng, X., Zhang, X., Wu, Z., & Weng, P. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.07.208 · Cited by 98
Levi, I., Gurevich, M., Perlman, G., Magalashvili, D., Menascu, S., Bar, N., Godneva, A., Zahavi, L., Chermon, D., Kosower, N., et al. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100246 · Cited by 99
The Place of Stress and Emotions in the Irritable Bowel Syndrome
Sonia Pellissier, A., & Bonaz, B. L. (2016) · Vitamins and hormones · doi:10.1016/bs.vh.2016.09.005 · Cited by 102
Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms
Camilleri, M. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.270892 · Cited by 98
“when intestinal permeability is increased, through direct stimulation of host cells in the lamina propria (Rhee et al. 2009).”
BackgroundInsights into drug discovery from natural medicines using reverse pharmacokinetics
Hao, H., Zheng, X., & Wang, G. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.02.001 · Cited by 99
Chemotaxis of Escherichia coli to major hormones and polyamines present in human gut
Lopes, J., & Sourjik, V. (2018) · The ISME Journal · doi:10.1038/s41396-018-0227-5 · Cited by 94
Feeding melancholic microbes: MyNewGut recommendations on diet and mood
Dinan, T. G., Stanton, C., Long-Smith, C., Kennedy, P., Cryan, J. F., Cowan, C. S. M., Cenit, M. C., van der Kamp, J.-W., & Sanz, Y. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.11.010 · Cited by 95
“We know that the brain-gut-microbiota axis is a bidirectional communication systemwhich enables gut microbes to communicate with the brain, and the brain in turn to communicate with the gut [16].”
BackgroundChallenges in IBD Research: Environmental Triggers
Ho, S., Lewis, J. D., Mayer, E. A., Bernstein, C. N., Plevy, S. E., Chuang, E., Rappaport, S. M., Croitoru, K., Korzenik, J. R., Krischer, J. P., et al. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz076 · Cited by 100
“10 13 The sensitivity and responsiveness to stress is determined by genetic and epigenetic factors on the stress system and different brain networks the latter including the epigenetic effects within the hypothalamic pituitary (HPA) axis in response to exposure to early adverse life events.”
BackgroundSelf-citationHelicobacter pylori Infection and Extragastric Diseases—A Focus on the Central Nervous System
Baj, J., Forma, A., Flieger, W., Morawska, I., Michalski, A., Buszewicz, G., Sitarz, R., Portincasa, P., Garruti, G., Flieger, M., et al. (2021) · Cells · doi:10.3390/cells10092191 · Cited by 100
“Abbreviations AD Alzheimer’s disease AIDP Acute inflammatory demyelinating polyneuropathy AMAN Acute motor axonal neuropathy AMSAN Acute motor and sensory axonal neuropathy ANS Autonomic nervous system ApoE4 Apolioprotein E4 BBB Brain-blood-barrier BBE Bickerstaff brainstem encephalitis BMD-MCs Bone marrow-derived mas…”
BackgroundAdak, A., Maity, C., Ghosh, K., Pati, B. R., & Mondal, K. C. (2013) · Folia Microbiologica · doi:10.1007/s12223-013-0241-y · Cited by 94
Intervention strategies for cesarean section–induced alterations in the microbiota-gut-brain axis
Moya-Pérez, Á., Luczynski, P., Renes, I. B., Wang, S., Borre, Y. E., Ryan, C. A., Knol, J., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017) · Nutrition Reviews · doi:10.1093/nutrit/nuw069 · Cited by 100
The connection between microbiome and schizophrenia
Golofast, B., & Vales, K. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.12.011 · Cited by 92
Donoso, F., Egerton, S., Bastiaanssen, T. F. S., Fitzgerald, P., Gite, S., Fouhy, F., Ross, R. P., Stanton, C., Dinan, T. G., & Cryan, J. F. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104673 · Cited by 92
Stress-Related Alterations of Visceral Sensation: Animal Models for Irritable Bowel Syndrome Study
Larauche, M. H., Mulak, A., & Taché, Y. (2011) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm.2011.17.3.213 · Cited by 92
“sensory-motor function indicate a novel approach to IBS treatment with a use of probiotics, prebiotics and antibiotics.(260,308)”
MethodGut Microbiota: A Modulator of Brain Plasticity and Cognitive Function in Ageing
Leung, K., & Thuret, S. (2015) · Healthcare · doi:10.3390/healthcare3040898 · Cited by 94
Targeting the gut microbiota to influence brain development and function in early life
Wang, S., Harvey, L., Martı́n, R., van der Beek, E. M., Knol, J., Cryan, J. F., & Renes, I. B. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.002 · Cited by 97
Bajramagić, S., Hodžić, E., Mulabdić, A., Holjan, S., Vinčević-Smajlović, S., & Rovcanin, A. (2019) · Medical Archives · doi:10.5455/medarh.2019.73.316-320 · Cited by 94
“However, most of the evidence has been derived from animal studies, and their effect in humans is unclear due to a small number of studies on humans (16).”
BackgroundNeuropeptides in gut-brain axis and their influence on host immunity and stress
Wei, P., Keller, C., & Li, L. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.02.018 · Cited by 97
“The remaining extrinsic nerves connect the central nervous system with the gut and belong either to the afferent gut-brain or the efferent brain-gut axis [13,14].”
BackgroundGut : liver : brain axis: the microbial challenge in the hepatic encephalopathy
Mancini, A., Campagna, F., Amodio, P., & Tuohy, K. M. (2018) · Food & Function · doi:10.1039/c7fo01528c · Cited by 89
The microbiome as a novel paradigm in studying stress and mental health.
Liu, R. T. (2017) · American Psychologist · doi:10.1037/amp0000058 · Cited by 96
“…and brain has been well established, the influence of enteric microbiota on this system has gained increasing prominence in recent years, leading to an extension of the gut–brain axis to a microbiota–gut–brain axis (Collins, Surette, & Bercik, 2012; Foster & McVey Neufeld, 2013; Rhee et al., 2009).”
BackgroundYasukawa, Z., Inoue, R., Ozeki, M., Okubo, T., Takagi, T., Honda, A., & Naito, Y. (2019) · Nutrients · doi:10.3390/nu11092170 · Cited by 89
“PHGG relieves IBS symptoms in patients at 5–11 g/day [36].”
BackgroundInfluentialGut-Brain Axis in the Early Postnatal Years of Life: A Developmental Perspective
Jena, A., Montoya, C. A., Mullaney, J. A., Dilger, R. N., Young, W., McNabb, W. C., & Roy, N. C. (2020) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2020.00044 · Cited by 98
Interactions between the microbiota and enteric nervous system during gut-brain disorders
Fried, S. G., Wemelle, E., Cani, P. D., & Knauf, C. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108721 · Cited by 95
The Microbiota–Gut–Brain Axis and Neurological Disorders: A Comprehensive Review
Nakhal, M. M., Yassin, L. K., Alyaqoubi, R., Saeed, S., Alderei, A., Alhammadi, A., Alshehhi, M., Almehairbi, A., Houqani, S. A., BaniYas, S., et al. (2024) · Life · doi:10.3390/life14101234 · Cited by 136
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
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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.
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