Microbial Endocrinology in the Microbiome-Gut-Brain Axis: How Bacterial Production and Utilization of Neurochemicals Influence Behavior
Open accessAbstract
The ability of bacterial pathogens to influence behavior has been recognized for decades, most notably bacteria that directly invade the nervous system. However, increasing evidence is mounting that microorganisms may directly interact with elements
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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 microbially-modulated metabolite 4-ethylphenylsulfate is sufficient to induce anxiety-like behavior in mice.
“Multiple research groups (Chey et al., 2001;Hsiao et al., 2013;Lyte, 2013;Sokol and Adolph, 2018;Wall et al., 2014) have demonstrated that the microbially-modulated metabolite 4-ethylphenylsulfate is sufficient to induce anxiety-like behavior in mice.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Lyte, 2013
The section “What Is Known—Associations of Microbes with Behavior” reports that Campylobacter jejuni can induce anxiety-like behavior in mice, but does not attribute that effect to 4-ethylphenylsulfate. Searches of our full-text copy for the metabolite and its proposed effect found no passage addressing whether 4-ethylphenylsulfate itself is sufficient to induce that behavior. No page number is available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gut–brain axis: How the microbiome influences anxiety and depression
Foster, J. A., & McVey Neufeld, K.-A. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.01.005 · Cited by 2,460 · cited 1× · see citing works
“This gut-to-brain communication has been the subject of intensive study for many years and is recognized to play an important role in the ability of gut-related pathologies to also result in mental health–related issues such as depression [17].”
BackgroundLyte, M., Varcoe, J. J., & Bailey, M. T. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00145-0 · Cited by 218 · cited 2× · see citing works
“jejuni [5] as described above and subsequent reports identifying the neural substrates both within the brain and vagalmediated gut-to-brain pathway [6].”
BackgroundSelf-citation
Flagged first, then by citations
Research works printed but not linked: 21
- [1]Lyte M (1993) The role of microbial endocrinology in infectious disease. J Endocrinol 137: 343– 345. 8371072
- [2]Berdoy M, Webster JP, Macdonald DW (2000) Fatal attraction in rats infected with Toxoplasma gondii. Proc Biol Sci 267: 1591– 1594. 11007336 PMC1690701
- [3]Blanchard EB, Scharff L, Schwarz SP, Suls JM, Barlow DH (1990) The role of anxiety and depression in the irritable bowel syndrome. Behav Res Ther 28: 401– 405. 2256898
- [4]Wood JD (2004) Enteric neuroimmunophysiology and pathophysiology. Gastroenterology 127: 635– 657. 15300595
- [6]Goehler LE, Gaykema RPA, Opitz N, Reddaway R, Badr N, et al (2005) Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun 19: 334– 344. 15944073
- [7]Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13: 701– 712. 22968153
- [8]Lyte M (2010) The microbial organ in the gut as a driver of homeostasis and disease. Med Hypotheses 74: 634– 638. 19900764
- [9]Roshchina VV (2010) Evolutionary considerations of neurotransmitters in microbial, plant and animal cells. In: Lyte M, Freestone PP, editors. Microbial endocrinology: interkingdom signaling in infectious disease and health. New York: Springer. pp. 17–52.
- [10]Iyer LM, Aravind L, Coon SL, Klein DC, Koonin EV (2004) Evolution of cell-cell signaling in animals: did late horizontal gene transfer from bacteria have a role? Trends Genet 20: 292– 299. 15219393
- [11]Lyte M, Ernst S (1992) Catecholamine induced growth of gram negative bacteria. Life Sci 50: 203– 212. 1731173
- [12]Lyte M (2010) Microbial endocrinology: a personal journey. In: Lyte M, Freestone PPE, editors. Microbial endocrinology: interkingdom signaling in infectious disease and health. New York: Springer. pp. 1–16.
- [13]Peterson G, Kumar A, Gart E, Narayanan S (2011) Catecholamines increase conjugative gene transfer between enteric bacteria. Microb Pathog 51: 1– 8. 21419838
- [14]Yurdaydin C, Walsh TJ, Engler HD, Ha JH, Li Y, et al (1995) Gut bacteria provide precursors of benzodiazepine receptor ligands in a rat model of hepatic encephalopathy. Brain Res 679: 42– 48. 7648264
- [15]Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9: 286– 294. 22392290
- [16]Breer H, Eberle J, Frick C, Haid D, Widmayer P (2012) Gastrointestinal chemosensation: chemosensory cells in the alimentary tract. Histochem Cell Biol 138: 13– 24. 22527698
- [18]Green BT, Lyte M, Chen C, Xie Y, Casey MA, et al (2004) Adrenergic modulation of Escherichia coli O157:H7 adherence to the colonic mucosa. Am J Physiol Gastrointest Liver Physiol 287: G1238– 1246. 15534374
- [19]Neufeld KM, Kang N, Bienenstock J, Foster JA (2011) Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 23: 255– 264, e119. 21054680
- [20]Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, et al (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108: 16050– 16055. 21876150 PMC3179073
- [21]Li W, Dowd S, Scurlock B, Acosta-Martinez V, Lyte M (2009) Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria. Physiol Behav 96: 557– 567. 19135464
- [22]Douglas-Escobar M, Elliott E, Neu J (2013) Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr 167: 374– 379. 23400224
- [23]Norris V, Molina F, Gewirtz AT (2013) Hypothesis: bacteria control host appetites. J Bacteriol 195: 411– 416. 23144247 PMC3554020
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Interactions between the microbiota, immune and nervous systems in health and disease
Fung, T. C., Olson, C. A., & Hsiao, E. Y. (2017) · Nature Neuroscience · doi:10.1038/nn.4476 · Cited by 1,900 · see citing works
Gut/brain axis and the microbiota
Mayer, E. A., Tillisch, K., & Gupta, A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76304 · Cited by 1,503 · see citing works
Minireview: Gut microbiota: The neglected endocrine organ
Clarke, G., Stilling, R. M., Kennedy, P. J., Stanton, C., Cryan, J. F., & Dinan, T. G. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1108 · Cited by 1,192 · see citing works
The microbiome-gut-brain axis in health and disease
Dinan, T. G., & Cryan, J. F. (2017) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2016.09.007 · Cited by 1,111 · see citing works
Control of brain development, function, and behavior by the microbiome
Sampson, T. R., & Mazmanian, S. K. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.011 · Cited by 1,093 · see citing works
Gut microbes and the brain: paradigm shift in neuroscience
Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F., & Tillisch, K. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3299-14.2014 · Cited by 1,033 · see citing works
The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis
Stilling, R. M., van de Wouw, M., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.06.011 · Cited by 891 · see citing works
Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration
Dinan, T. G., & Cryan, J. F. (2017) · The Journal of Physiology · doi:10.1113/jp273106 · Cited by 813 · see citing works
Luczynski, P., McVey Neufeld, K.-A., Oriach, C. S., Clarke, G., Dinan, T. G., & Cryan, J. F. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw020 · Cited by 632 · see citing works
Collective unconscious: How gut microbes shape human behavior
Dinan, T. G., Stilling, R. M., Stanton, C., & Cryan, J. F. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.02.021 · Cited by 571 · see citing works
Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity
Bruce-Keller, A. J., Salbaum, J. M., Luo, M., Blanchard, E., Taylor, C. M., Welsh, D. A., & Berthoud, H.-R. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.07.012 · Cited by 563 · see citing works
Specialized metabolites from the microbiome in health and disease
Sharon, G., Garg, N., Debelius, J., Knight, R., Dorrestein, P. C., & Mazmanian, S. K. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.016 · Cited by 544 · see citing works
The microbiome: a key regulator of stress and neuroinflammation
Rea, K., Dinan, T. G., & Cryan, J. F. (2016) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.03.001 · Cited by 508 · see citing works
Role of TLR4 in the gut-brain axis in Parkinson's disease: A translational study from men to mice
Perez-Pardo, P., Dodiya, H. B., Engen, P. A., Forsyth, C. B., Huschens, A. M., Shaikh, M., Voigt, R. M., Naqib, A., Green, S. J., Kordower, J. H., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-316844 · Cited by 467 · see citing works
Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease
Kesika, P., Suganthy, N., Sivamaruthi, B. S., & Chaiyasut, C. (2021) · Life Sciences · doi:10.1016/j.lfs.2020.118627 · Cited by 479 · see citing works
Microbiota-gut-brain axis: Modulator of host metabolism and appetite
van de Wouw, M., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2017) · The Journal of Nutrition · doi:10.3945/jn.116.240481 · Cited by 461 · see citing works
Leclercq, S., Mian, F. M., Stanisz, A. M., Bindels, L. B., Cambier, E., Ben-Amram, H., Koren, O., Forsythe, P., & Bienenstock, J. (2017) · Nature Communications · doi:10.1038/ncomms15062 · Cited by 434 · see citing works
Zaborin, A., Smith, D., Garfield, K., Quensen, J., Shakhsheer, B., Kade, M., Tirrell, M., Tiedje, J., Gilbert, J. A., Zaborina, O., et al. (2014) · mBio · doi:10.1128/mbio.01361-14 · Cited by 367 · see citing works
Why does the microbiome affect behaviour?
Johnson, K. V.-A., & Foster, K. R. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0014-3 · Cited by 333 · see citing works
Brain-Gut-Microbiota Axis and Mental Health
Dinan, T. G., & Cryan, J. F. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000519 · Cited by 325 · see citing works
Microbiota regulation of the mammalian gut-brain axis
Burokas, A., Moloney, R. D., Dinan, T. G., & Cryan, J. F. (2015) · Advances in applied microbiology · doi:10.1016/bs.aambs.2015.02.001 · Cited by 300 · see citing works
Cross talk: the microbiota and neurodevelopmental disorders
Kelly, J. R., Minuto, C., Cryan, J. F., Clarke, G., & Dinan, T. G. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00490 · Cited by 271 · see citing works
Pirbaglou, M., Katz, J., de Souza, R. J., Stearns, J. C., Motamed, M., & Ritvo, P. (2016) · Nutrition Research · doi:10.1016/j.nutres.2016.06.009 · Cited by 270 · see citing works
Stilling, R. M., Ryan, F. J., Hoban, A. E., Shanahan, F., Clarke, G., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.07.009 · Cited by 233 · see citing works
The microbiome in posttraumatic stress disorder and trauma-exposed controls: an exploratory study
Hemmings, S. M. J., Malan-Müller, S., van den Heuvel, L. L., Demmitt, B. A., Stanislawski, M. A., Smith, D. G., Bohr, A. D., Stamper, C. E., Hyde, E. R., Morton, J. T., et al. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000512 · Cited by 208 · see citing works
Steroids, stress and the gut microbiome-brain axis
Tetel, M. J., de Vries, G. J., Melcangi, R. C., Panzica, G., & O'Mahony, S. M. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12548 · Cited by 187 · see citing works
A psychology of the human brain-gut-microbiome axis
Allen, A. P., Dinan, T. G., Clarke, G., & Cryan, J. F. (2017) · Social and Personality Psychology Compass · doi:10.1111/spc3.12309 · Cited by 174 · see citing works
The effects of dairy and dairy derivatives on the gut microbiota: a systematic literature review
Aslam, H., Marx, W., Rocks, T., Loughman, A., Chandrasekaran, V., Ruusunen, A., Dawson, S. L., West, M., Mullarkey, E., Pasco, J. A., et al. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1799533 · Cited by 170 · see citing works
Gut hormones in microbiota-gut-brain cross-talk
Sun, L.-J., Li, J.-N., & Nie, Y.-Z. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000706 · Cited by 145 · see citing works
Relevance of gutmicrobiota in cognition, behaviour and Alzheimer’s disease
de J.R. De-Paula, V., Forlenza, A. S., & Forlenza, O. V. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.07.007 · Cited by 145 · see citing works
Pelsser, L. M., Frankena, K., Toorman, J., & Rodrigues Pereira, R. (2017) · PLOS ONE · doi:10.1371/journal.pone.0169277 · Cited by 145 · see citing works
Gut microbes in neurocognitive and mental health disorders
Halverson, T., & Alagiakrishnan, K. (2020) · Annals of Medicine · doi:10.1080/07853890.2020.1808239 · Cited by 125 · see citing works
Posttraumatic stress disorder: does the gut microbiome hold the key?
Leclercq, S., Forsythe, P., & Bienenstock, J. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716635535 · Cited by 121 · see citing works
Stress matters: randomized controlled trial on the effect of probiotics on neurocognition
Papalini, S., Michels, F., Kohn, N., Wegman, J., van Hemert, S., Roelofs, K., Arias-Vasquez, A., & Aarts, E. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.100141 · Cited by 123 · see citing works
Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice
Stilling, R. M., Moloney, G. M., Ryan, F. J., Hoban, A. E., Bastiaanssen, T. F., Shanahan, F., Clarke, G., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2018) · eLife · doi:10.7554/elife.33070 · Cited by 106 · see citing works
The effect of the stress hormone cortisol on the metatranscriptome of the oral microbiome
Duran-Pinedo, A. E., Solbiati, J., & Frias-Lopez, J. (2018) · npj Biofilms and Microbiomes · doi:10.1038/s41522-018-0068-z · Cited by 96 · see citing works
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 · see citing works
Bruce-Keller, A. J., Fernandez-Kim, S.-O., Townsend, R. L., Kruger, C., Carmouche, R., Newman, S., Salbaum, J. M., & Berthoud, H.-R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175577 · Cited by 76 · see citing works
Moloney, G. M., O’Leary, O. F., Salvo-Romero, E., Desbonnet, L., Shanahan, F., Dinan, T. G., Clarke, G., & Cryan, J. F. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.07.026 · Cited by 68 · see citing works
Advances in Gut Microbiota of Viral Hepatitis Cirrhosis
Wang, Y., Pan, C. Q., & Xing, H. (2019) · BioMed Research International · doi:10.1155/2019/9726786 · Cited by 52 · see citing works
Microalgae in Terms of Biomedical Technology: Probiotics, Prebiotics, and Metabiotics
Oleskin, A. V., & Boyang, C. (2022) · Applied Biochemistry and Microbiology · doi:10.1134/s0003683822060126 · Cited by 27 · see citing works
Lewis, N., Villani, A., & Lagopoulos, J. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.01.031 · Cited by 25 · see citing works
- Authors
- Lyte, M.
- Affiliations
- Texas Tech University Health Sciences Center (US)
- Corresponding author
- Lyte, Mark
- ORCID
- Lyte, Mark
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-11-14
- Volume
- 9
- Issue
- 11
- Pages
- e1003726
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC3828163
- OpenAlex
- W1989957107
- Cited by
- 399
- References
- 2
- Citations by year
- 2026: 24 · 2025: 36 · 2024: 28 · 2023: 34 · 2022: 37 · 2021: 31 · 2020: 42 · 2019: 32 · 2018: 41 · 2017: 31 · 2016: 31 · 2015: 19 · 2014: 13
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- microbial endocrinology, microbiome-gut-brain axis, neurochemicals, interkingdom signaling, horizontal gene transfer, host behavior, psychiatric treatment, gut microbiota
- MeSH terms
- Animals, Bacteria, Hormones, Humans, Intestines, Neurosecretory Systems, Bacterial Physiological Phenomena, Host-Pathogen Interactions, Microbiota
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.
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
