The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications
Open accessAbstract
Background & aims Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders.Methods We reviewed the preclinical and clinical literature related to the topic of brain gut microbiome interactions.Results Well-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programmed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established.Conclusions Targets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders.
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?
Many psychobiotics are being tested to identify possible therapeutic benefits.
“At the moment, many psychobiotics, being them prebiotics, probiotics, postbiotics, and even single molecules involved in the gut microbial signaling, are being tested to identify any possible therapeutic benefits [116,120].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [120]
Probiotics can affect the CNS by regulating the intestinal flora and preventing mental diseases through the gut-brain axis.
“several research findings have shown that probiotics can affect the CNS by regulating the intestinal flora and preventing mental diseases through the gut–brain axis [71,72,73].”
From Probiotics Regulate Gut Microbiota: An Effective Method to Improve Immunity (2021) · cites this paper as [71]
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
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 · see citing works
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100 · see citing works
A core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823 · see citing works
Linking long-term dietary patterns with gut microbial enterotypes
Wu, G. D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y.-Y., Keilbaugh, S. A., Bewtra, M., Knights, D., Walters, W. A., Knight, R., et al. (2011) · Science · doi:10.1126/science.1208344 · Cited by 6,513 · see citing works
Diversity, stability and resilience of the human gut microbiota
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012) · Nature · doi:10.1038/nature11550 · Cited by 5,533 · see citing works
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413 · see citing works
Dominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774 · see citing works
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572 · see citing works
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554 · see citing works
Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., & Cryan, J. F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102999108 · Cited by 3,888 · see citing works
Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.018 · Cited by 3,622 · see citing works
Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015) · Cell · doi:10.1016/j.cell.2015.02.047 · Cited by 3,614 · see citing works
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569 · see citing works
Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life
Bäckhed, F., Roswall, J., Peng, Y., Feng, Q., Jia, H., Kovatcheva-Datchary, P., Li, Y., Xia, Y., Xie, H., Zhong, H., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.004 · Cited by 3,315 · see citing works
Development of the Human Infant Intestinal Microbiota
Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A., & Brown, P. O. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050177 · Cited by 2,877 · see citing works
Desai, M. S., Seekatz, A. M., Koropatkin, N. M., Kamada, N., Hickey, C. A., Wolter, M., Pudlo, N. A., Kitamoto, S., Terrapon, N., Muller, A., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.043 · Cited by 2,805 · see citing works
Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites
Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., & Siuzdak, G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812874106 · Cited by 2,677 · see citing works
The gut microbiota influences blood-brain barrier permeability in mice
Braniste, V., Al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., Tóth, M., Korecka, A., Bakocevic, N., Ng, L. G., Kundu, P., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009759 · Cited by 2,530 · see citing works
Dethlefsen, L., & Relman, D. A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000087107 · Cited by 2,421 · see citing works
Brown, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., Muir, A. I., Wigglesworth, M. J., Kinghorn, I., Fraser, N. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211609200 · Cited by 2,409 · see citing works
Tolhurst, G., Heffron, H., Lam, Y. S., Parker, H. E., Habib, A. M., Diakogiannaki, E., Cameron, J., Grosse, J., Reimann, F., & Gribble, F. M. (2012) · Diabetes · doi:10.2337/db11-1019 · Cited by 2,404 · see citing works
Mapping cortical change across the human life span
Sowell, E. R., Peterson, B. S., Thompson, P. M., Welcome, S. E., Henkenius, A. L., & Toga, A. W. (2003) · Nature Neuroscience · doi:10.1038/nn1008 · Cited by 2,328 · see citing works
Gut microbiome alterations in Alzheimer’s disease
Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-13601-y · Cited by 2,137 · see citing works
Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Vijay-Kumar, M., Aitken, J. D., Carvalho, F. A., Cullender, T. C., Mwangi, S., Srinivasan, S., Sitaraman, S. V., Knight, R., Ley, R. E., & Gewirtz, A. T. (2010) · Science · doi:10.1126/science.1179721 · Cited by 2,068 · see citing works
Zheng, P., Zeng, B., Zhou, C., Liu, M., Fang, Z., Xu, X., Zeng, L., Chen, J., Fan, S., Du, X., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.44 · Cited by 2,023 · see citing works
Lloyd-Price, J., Abu-Ali, G., & Huttenhower, C. (2016) · Genome Medicine · doi:10.1186/s13073-016-0307-y · Cited by 1,891 · see citing works
Human gut microbiota in obesity and after gastric bypass
Zhang, H., DiBaise, J. K., Zuccolo, A., Kudrna, D., Braidotti, M., Yu, Y., Parameswaran, P., Crowell, M. D., Wing, R., Rittmann, B. E., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812600106 · Cited by 1,880 · see citing works
Diet-induced extinctions in the gut microbiota compound over generations
Sonnenburg, E. D., Smits, S. A., Tikhonov, M., Higginbottom, S. K., Wingreen, N. S., & Sonnenburg, J. L. (2016) · Nature · doi:10.1038/nature16504 · Cited by 1,730 · see citing works
Gut feelings: the emerging biology of gut-brain communication
Mayer, E. A. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3071 · Cited by 1,726 · see citing works
Self-citationKelly, J. R., Borre, Y., O' Brien, C., Patterson, E., El Aidy, S., Deane, J., Kennedy, P. J., Beers, S., Scott, K., Moloney, G., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.07.019 · Cited by 1,683 · see citing works
The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota
Round, J. L., Lee, S. M., Li, J., Tran, G., Jabri, B., Chatila, T. A., & Mazmanian, S. K. (2011) · Science · doi:10.1126/science.1206095 · Cited by 1,604 · see citing works
Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., Hammer, R. E., Williams, S. C., Crowley, J., Yanagisawa, M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808567105 · Cited by 1,564 · see citing works
Rothhammer, V., Mascanfroni, I. D., Bunse, L., Takenaka, M. C., Kenison, J. E., Mayo, L., Chao, C.-C., Patel, B., Yan, R., Blain, M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4106 · Cited by 1,559 · see citing works
Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., Ferrari, C., Guerra, U. P., Paghera, B., Muscio, C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.019 · Cited by 1,382 · see citing works
Lin, H. V., Frassetto, A., Kowalik Jr, E. J., Nawrocki, A. R., Lu, M. M., Kosinski, J. R., Hubert, J. A., Szeto, D., Yao, X., Forrest, G., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035240 · Cited by 1,378 · see citing works
Diversity of astrocyte functions and phenotypes in neural circuits
Khakh, B. S., & Sofroniew, M. V. (2015) · Nature Neuroscience · doi:10.1038/nn.4043 · Cited by 1,239 · see citing works
Consumption of fermented milk product with probiotic modulates brain activity
Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., Guyonnet, D., Legrain–Raspaud, S., Trotin, B., Naliboff, B., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.02.043 · Cited by 1,192 · see citing works
Self-citationMicroglia development follows a stepwise program to regulate brain homeostasis
Matcovitch-Natan, O., Winter, D. R., Giladi, A., Vargas Aguilar, S., Spinrad, A., Sarrazin, S., Ben-Yehuda, H., David, E., Zelada González, F., Perrin, P., et al. (2016) · Science · doi:10.1126/science.aad8670 · Cited by 1,180 · see citing works
Differential Adaptation of Human Gut Microbiota to Bariatric Surgery–Induced Weight Loss
Furet, J.-P., Kong, L.-C., Tap, J., Poitou, C., Basdevant, A., Bouillot, J.-L., Mariat, D., Corthier, G., Doré, J., Henegar, C., et al. (2010) · Diabetes · doi:10.2337/db10-0253 · Cited by 1,173 · see citing works
The blood-brain barrier in systemic inflammation
Varatharaj, A., & Galea, I. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.03.010 · Cited by 1,172 · see citing works
Microglia development and function
Nayak, D., Roth, T. L., & McGavern, D. B. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120240 · Cited by 1,154 · see citing works
Bailey, M. T., Dowd, S. E., Galley, J. D., Hufnagle, A. R., Allen, R. G., & Lyte, M. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.023 · Cited by 1,123 · see citing works
Kelly, J. R., Kennedy, P. J., Cryan, J. F., Dinan, T. G., Clarke, G., & Hyland, N. P. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00392 · Cited by 1,110 · 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
Microbiota and neurodevelopmental windows: implications for brain disorders
Borre, Y. E., O’Keeffe, G. W., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.05.002 · Cited by 1,089 · see citing works
Everard, A., Lazarevic, V., Derrien, M., Girard, M., Muccioli, G. G., Neyrinck, A. M., Possemiers, S., Van Holle, A., François, P., de Vos, W. M., et al. (2011) · Diabetes · doi:10.2337/db11-0227 · Cited by 1,076 · see citing works
The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet
Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018) · Cell · doi:10.1016/j.cell.2018.04.027 · Cited by 1,057 · see citing works
Rajilić–Stojanović, M., Biagi, E., Heilig, H. G. H. J., Kajander, K., Kekkonen, R. A., Tims, S., & de Vos, W. M. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.043 · Cited by 1,041 · see citing works
Vandeputte, D., Falony, G., Vieira-Silva, S., Tito, R. Y., Joossens, M., & Raes, J. (2016) · Gut · doi:10.1136/gutjnl-2015-309618 · Cited by 1,028 · see citing works
Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer
Dominguez-Bello, M. G., De Jesus-Laboy, K. M., Shen, N., Cox, L. M., Amir, A., Gonzalez, A., Bokulich, N. A., Song, S. J., Hoashi, M., Rivera-Vinas, J. I., et al. (2016) · Nature Medicine · doi:10.1038/nm.4039 · Cited by 1,014 · see citing works
Jakobsson, H. E., Abrahamsson, T. R., Jenmalm, M. C., Harris, K., Quince, C., Jernberg, C., Björkstén, B., Engstrand, L., & Andersson, A. F. (2014) · Gut · doi:10.1136/gutjnl-2012-303249 · Cited by 1,011 · see citing works
Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity
Liou, A. P., Paziuk, M., Luevano, J.-M., Machineni, S., Turnbaugh, P. J., & Kaplan, L. M. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005687 · Cited by 1,007 · see citing works
Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression
Desbonnet, L., Garrett, L., Clarke, G., Kiely, B., Cryan, J. F., & Dinan, T. G. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.08.005 · Cited by 999 · see citing works
Burokas, A., Arboleya, S., Moloney, R. D., Peterson, V. L., Murphy, K., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.12.031 · Cited by 952 · see citing works
Intestinal microbiota in functional bowel disorders: a Rome foundation report
Simrén, M., Barbara, G., Flint, H. J., Spiegel, B. M. R., Spiller, R. C., Vanner, S., Verdu, E. F., Whorwell, P. J., & Zoetendal, E. G. (2013) · Gut · doi:10.1136/gutjnl-2012-302167 · Cited by 939 · see citing works
Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine
Haghikia, A., Jörg, S., Duscha, A., Berg, J., Manzel, A., Waschbisch, A., Hammer, A., Lee, D.-H., May, C., Wilck, N., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.09.007 · Cited by 927 · see citing works
Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania
Smits, S. A., Leach, J., Sonnenburg, E. D., Gonzalez, C. G., Lichtman, J. S., Reid, G., Knight, R., Manjurano, A., Changalucha, J., Elias, J. E., et al. (2017) · Science · doi:10.1126/science.aan4834 · Cited by 886 · see citing works
The Gut Microbiota and Alzheimer’s Disease
Jiang, C., Li, G., Huang, P., Liu, Z., & Zhao, B. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161141 · Cited by 852 · see citing works
An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota
Jeffery, I. B., O'Toole, P. W., Öhman, L., Claesson, M. J., Deane, J., Quigley, E. M. M., & Simrén, M. (2012) · Gut · doi:10.1136/gutjnl-2011-301501 · Cited by 835 · see citing works
Pinto-Sanchez, M. I., Hall, G. B., Ghajar, K., Nardelli, A., Bolino, C., Lau, J. T., Martin, F.-P., Cominetti, O., Welsh, C., Rieder, A., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.05.003 · Cited by 821 · see citing works
Akkasheh, G., Kashani-Poor, Z., Tajabadi-Ebrahimi, M., Jafari, P., Akbari, H., Taghizadeh, M., Memarzadeh, M. R., Asemi, Z., & Esmaillzadeh, A. (2016) · Nutrition · doi:10.1016/j.nut.2015.09.003 · Cited by 767 · see citing works
Cani, P. D., Lecourt, E., Dewulf, E. M., Sohet, F. M., Pachikian, B. D., Naslain, D., Backer, F. D., Neyrinck, A. M., & Delzenne, N. M. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.28095 · Cited by 763 · see citing works
Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour
Desbonnet, L., Clarke, G., Traplin, A., O’Sullivan, O., Crispie, F., Moloney, R. D., Cotter, P. D., Dinan, T. G., & Cryan, J. F. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.04.004 · Cited by 760 · see citing works
Tremaroli, V., Karlsson, F., Werling, M., Ståhlman, M., Kovatcheva-Datchary, P., Olbers, T., Fändriks, L., le Roux, C. W., Nielsen, J., & Bäckhed, F. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.009 · Cited by 757 · see citing works
Xiong, Y., Miyamoto, N., Shibata, K., Valasek, M. A., Motoike, T., Kedzierski, R. M., & Yanagisawa, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2637002100 · Cited by 731 · see citing works
Kynurenine pathway metabolism and the microbiota-gut-brain axis
Kennedy, P. J., Cryan, J. F., Dinan, T. G., & Clarke, G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.002 · Cited by 724 · see citing works
Tap, J., Derrien, M., Törnblom, H., Brazeilles, R., Cools-Portier, S., Doré, J., Störsrud, S., Le Nevé, B., Öhman, L., & Simrén, M. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.09.049 · Cited by 642 · see citing works
Regulation of prefrontal cortex myelination by the microbiota
Hoban, A. E., Stilling, R. M., Ryan, F. J., Shanahan, F., Dinan, T. G., Claesson, M. J., Clarke, G., & Cryan, J. F. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.42 · Cited by 635 · see citing works
IL-1β Causes an Increase in Intestinal Epithelial Tight Junction Permeability
Al-Sadi, R. M., & Ma, T. Y. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4641 · Cited by 601 · see citing works
Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder
Vuong, H. E., & Hsiao, E. Y. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.08.024 · Cited by 595 · see citing works
Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells
Chimerel, C., Emery, E., Summers, D. K., Keyser, U., Gribble, F. M., & Reimann, F. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.032 · Cited by 548 · see citing works
Infant gut microbiome associated with cognitive development
Carlson, A. L., Xia, K., Azcarate-Peril, M. A., Goldman, B. D., Ahn, M., Styner, M. A., Thompson, A. L., Geng, X., Gilmore, J. H., & Knickmeyer, R. C. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.06.021 · Cited by 541 · see citing works
Schmidt, K., Cowen, P. J., Harmer, C. J., Tzortzis, G., Errington, S., & Burnet, P. W. J. (2015) · Psychopharmacology · doi:10.1007/s00213-014-3810-0 · Cited by 522 · see citing works
Allen, A. P., Hutch, W., Borre, Y. E., Kennedy, P. J., Temko, A., Boylan, G., Murphy, E., Cryan, J. F., Dinan, T. G., & Clarke, G. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.191 · Cited by 513 · see citing works
De Palma, G., Lynch, M. D. J., Lu, J., Dang, V. T., Deng, Y., Jury, J., Umeh, G., Miranda, P. M., Pigrau Pastor, M., Sidani, S., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf6397 · Cited by 505 · see citing works
Brain gut microbiome interactions and functional bowel disorders
Mayer, E. A., Savidge, T., & Shulman, R. J. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.037 · Cited by 496 · see citing works
Self-citationCesarean Section and Chronic Immune Disorders
Sevelsted, A., Stokholm, J., Bønnelykke, K., & Bisgaard, H. (2015) · PEDIATRICS · doi:10.1542/peds.2014-0596 · Cited by 482 · see citing works
Metabolic surgery profoundly influences gut microbial–host metabolic cross-talk
Li, J. V., Ashrafian, H., Bueter, M., Kinross, J. K., Sands, C. J., le Roux, C. W., Bloom, S. R., Darzi, A. W., Athanasiou, T., Marchesi, J. R., et al. (2011) · Gut · doi:10.1136/gut.2010.234708 · Cited by 444 · see citing works
Goehler, L. E., Gaykema, R. P. A., Opitz, N., Reddaway, R., Badr, N., & Lyte, M. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.09.002 · Cited by 442 · see citing works
Graessler, J., Qin, Y., Zhong, H., Zhang, J., Licinio, J., Wong, M.-L., Xu, A., Chavakis, T., Bornstein, A. B., Ehrhart-Bornstein, M., et al. (2013) · The Pharmacogenomics Journal · doi:10.1038/tpj.2012.43 · Cited by 428 · see citing works
Slykerman, R. F., Hood, F., Wickens, K., Thompson, J. M. D., Barthow, C., Murphy, R., Kang, J., Rowden, J., Stone, P., Crane, J., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.09.013 · Cited by 422 · see citing works
Galley, J. D., Nelson, M. C., Yu, Z., Dowd, S. E., Walter, J., Kumar, P., Lyte, M., & Bailey, M. T. (2014) · BMC Microbiology · doi:10.1186/1471-2180-14-189 · Cited by 398 · see citing works
Microbial biofilms in the human gastrointestinal tract
Macfarlane, S., & Dillon, J. F. (2007) · Journal of Applied Microbiology · doi:10.1111/j.1365-2672.2007.03287.x · Cited by 379 · see citing works
Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles
Hubbard, T. D., Murray, I. A., Bisson, W. H., Lahoti, T. S., Gowda, K., Amin, S. G., Patterson, A. D., & Perdew, G. H. (2015) · Scientific Reports · doi:10.1038/srep12689 · Cited by 377 · see citing works
Houlden, A., Goldrick, M., Brough, D., Vizi, E. S., Lénárt, N., Martinecz, B., Roberts, I. S., & Dénes, Á. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.04.003 · Cited by 369 · see citing works
Functional dysbiosis within the gut microbiota of patients with constipated‐irritable bowel syndrome
Chassard, C., Dapoigny, M. C., Scott, K. P., Crouzet, L., Del’Homme, C., Marquet, P., Martin, J. C., Pickering, G. P., Ardid, D., Eschalier, A., et al. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2012.05007.x · Cited by 366 · see citing works
A meta-analysis of the use of probiotics to alleviate depressive symptoms
Ng, Q. X., Peters, C., Ho, C. Y. X., Lim, D. Y., & Yeo, W.-S. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.11.063 · Cited by 357 · see citing works
Kelly, J. R., Allen, A. P., Temko, A., Hutch, W., Kennedy, P. J., Farid, N., Murphy, E., Boylan, G., Bienenstock, J., Cryan, J. F., et al. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.11.018 · Cited by 355 · see citing works
Gut microbiome in ADHD and its relation to neural reward anticipation
Aarts, E., Ederveen, T. H. A., Naaijen, J., Zwiers, M. P., Boekhorst, J., Timmerman, H. M., Smeekens, S. P., Netea, M. G., Buitelaar, J. K., Franke, B., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183509 · Cited by 352 · see citing works
Tannock, G. W., & Savage, D. C. (1974) · Infection and Immunity · doi:10.1128/iai.9.3.591-598.1974 · Cited by 349 · see citing works
Food Addiction: Its Prevalence and Significant Association with Obesity in the General Population
Pedram, P., Wadden, D., Amini, P., Gulliver, W. P., Randell, E. W., Cahill, F., Vasdev, S., Goodridge, A., Carter, J. C., Zhai, G., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074832 · Cited by 338 · see citing works
Bauer, J., & Gerß, J. (2010) · Clinical Nutrition · doi:10.1016/j.clnu.2010.08.003 · Cited by 335 · see citing works
Jin, U.-H., Lee, S., Sridharan, G. V., Lee, K., Davidson, L. A., Jayaraman, A., Chapkin, R. S., Alaniz, R. C., & Safe, S. H. (2014) · Molecular Pharmacology · doi:10.1124/mol.113.091165 · Cited by 330 · see citing works
Jašarević, E., Howerton, C. L., Howard, C. D., & Bale, T. L. (2015) · Endocrinology · doi:10.1210/en.2015-1177 · Cited by 329 · see citing works
Romijn, A. R., Rucklidge, J. J., Kuijer, R. G., & Frampton, C. (2017) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867416686694 · Cited by 323 · see citing works
Human milk oligosaccharide consumption by intestinal microbiota
Marcobal, A. M., & Sonnenburg, J. L. (2012) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2012.03863.x · Cited by 311 · see citing works
Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase
Vogel, C. F. A., Goth, S. R., Dong, B., Pessah, I. N., & Matsumura, F. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.07.156 · Cited by 297 · see citing works
Damms-Machado, A., Mitra, S., Schollenberger, A. E., Kramer, K. M., Meile, T., Königsrainer, A., Huson, D. H., & Bischoff, S. C. (2015) · BioMed Research International · doi:10.1155/2015/806248 · Cited by 291 · see citing works
Roger, L. C., Costabile, A., Holland, D. T., Hoyles, L., & McCartney, A. L. (2010) · Microbiology · doi:10.1099/mic.0.043224-0 · Cited by 291 · see citing works
Prenatal Maternal Stress Associated with ADHD and Autistic Traits in early Childhood
Ronald, A., Pennell, C. E., & Whitehouse, A. (2011) · Frontiers in Psychology · doi:10.3389/fpsyg.2010.00223 · Cited by 289 · see citing works
Tarr, A. J., Galley, J. D., Fisher, S. E., Chichlowski, M., Berg, B. M., & Bailey, M. T. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.06.025 · Cited by 284 · see citing works
Labus, J. S., Hollister, E. B., Jacobs, J., Kirbach, K., Oezguen, N., Gupta, A., Acosta, J., Luna, R. A., Aagaard, K., Versalovic, J., et al. (2017) · Microbiome · doi:10.1186/s40168-017-0260-z · Cited by 284 · see citing works
Self-citationLong‐term monitoring of the human intestinal microbiota composition
Rajilić-Stojanović, M. D., Heilig, H. G. H. J., Tims, S., Zoetendal, E. G., & de Vos, W. M. (2012) · Environmental Microbiology · doi:10.1111/1462-2920.12023 · Cited by 268 · see citing works
Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat
Santos, J., Saunders, P. R., Hanssen, N. P. M., Yang, P., Yates, D. A., Groot, J. A., & Perdue, M. H. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.277.2.g391 · Cited by 251 · see citing works
Takada, M., Nishida, K., Kataoka‐Kato, A., Gondo, Y., Ishikawa, H., Suda, K., Kawai, M., Hoshi, R., Watanabe, O., Igarashi, T., et al. (2016) · Neurogastroenterology & Motility · doi:10.1111/nmo.12804 · Cited by 243 · see citing works
Antibiotic Exposure and the Risk for Depression, Anxiety, or Psychosis: A Nested Case-Control Study
Lurie, I., Yang, Y.-X., Haynes, K., Mamtani, R., & Boursi, B. (2015) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.15m09961 · Cited by 231 · see citing works
Acute maternal stress in pregnancy and schizophrenia in offspring: A cohort prospective study
Malaspina, D., Corcoran, C. M., Kleinhaus, K., Perrin, M., Fennig, S., Nahon, D., Friedlander, Y., & Harlap, S. (2008) · BMC Psychiatry · doi:10.1186/1471-244x-8-71 · Cited by 214 · see citing works
Winek, K., Engel, O., Bäcker‐Koduah, P., Heimesaat, M. M., Fischer, A., Bereswill, S., Dames, C., Kershaw, O., Gruber, A. D., Curato, C., et al. (2016) · Stroke · doi:10.1161/strokeaha.115.011800 · Cited by 214 · see citing works
Heijtz, R. D. (2016) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2016.04.012 · Cited by 193 · see citing works
Knowles, S. R., Nelson, E. A., & Palombo, E. A. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2007.09.010 · Cited by 192 · see citing works
Ryan, K. K., Kohli, R., Gutierrez-Aguilar, R., Gaitonde, S. G., Woods, S. C., & Seeley, R. J. (2013) · Endocrinology · doi:10.1210/en.2012-1891 · Cited by 185 · see citing works
Tillisch, K., Mayer, E. A., Gupta, A., Gill, Z., Brazeilles, R., Le Nevé, B., van Hylckama Vlieg, J. E. T., Guyonnet, D., Derrien, M., & Labus, J. S. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000493 · Cited by 185 · see citing works
Self-citationMarcelin, G., Jo, Y., Li, X., Schwartz, G. J., Zhang, Y., Dun, N. J., Lyu, R., Blouet, C., Chang, J. K., & Chua, S. C. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.10.002 · Cited by 168 · see citing works
Gut microbiota interacts with brain microstructure and function
Fernandez-Real, J.-M., Serino, M., Blasco, G., Puig, J., Daunis-i-Estadella, J., Ricart, W., Burcelin, R., Fernández-Aranda, F., & Portero-Otin, M. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3076 · Cited by 167 · see citing works
Activation of Enteroendocrine Cells via TLRs Induces Hormone, Chemokine, and Defensin Secretion
Palazzo, M., Balsari, A., Rossini, A., Selleri, S., Calcaterra, C., Gariboldi, S., Zanobbio, L., Arnaboldi, F., Shirai, Y. F., Serrao, G., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4296 · Cited by 147 · see citing works
Role of the aryl hydrocarbon receptor in drug metabolism
Ramadoss, P., Marcus, C. B., & Perdew, G. H. (2005) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.1.1.9 · Cited by 144 · see citing works
Goyal, M. S., Venkatesh, S., Milbrandt, J., Gordon, J. I., & Raichle, M. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511465112 · Cited by 141 · see citing works
Thum, C., Cookson, A. L., Otter, D. E., McNabb, W. C., Hodgkinson, A. J., Dyer, J. M., & Roy, N. C. (2012) · Journal of Nutrition · doi:10.3945/jn.112.166231 · Cited by 135 · see citing works
Van felius, I. D., Akkermans, L. M. A., Bosscha, K., Verheem, A., Harmsen, W., Visser, M. R., & Gooszen, H. G. (2003) · Neurogastroenterology & Motility · doi:10.1046/j.1365-2982.2003.00410.x · Cited by 134 · see citing works
FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic–pituitary–adrenal axis
Perry, R. J., Lee, S., Ma, L., Zhang, D., Schlessinger, J., & Shulman, G. I. (2015) · Nature Communications · doi:10.1038/ncomms7980 · Cited by 132 · see citing works
IL1β‐ and LPS‐induced serotonin secretion is increased in EC cells derived from Crohn’s disease
Kidd, M., Gustafsson, B. I., Drozdov, I., & Modlin, I. M. (2009) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01210.x · Cited by 130 · see citing works
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 · see citing works
Bala, V., Rajagopal, S., Kumar, D. P., Nalli, A. D., Mahavadi, S., Sanyal, A. J., Grider, J. R., & Murthy, K. S. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00420 · Cited by 124 · see citing works
The individual-specific and diverse nature of the preterm infant microbiota
Barrett, E., Kerr, C., Murphy, K., O'Sullivan, O., Ryan, C. A., Dempsey, E. M., Murphy, B. P., O'Toole, P. W., Cotter, P. D., Fitzgerald, G. F., et al. (2013) · Archives of Disease in Childhood - Fetal and Neonatal Edition · doi:10.1136/archdischild-2012-303035 · Cited by 120 · see citing works
Aguilera, M., Vergara, P., & Martínez, V. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12154 · Cited by 119 · see citing works
In vivo dynamics of innate immune sentinels in the CNS
Nayak, D., Zinselmeyer, B. H., Corps, K. N., & McGavern, D. B. (2012) · IntraVital · doi:10.4161/intv.22823 · Cited by 109 · see citing works
An unexplored brain-gut microbiota axis in stroke
Wen, S., & Wong, C. H. Y. (2017) · Gut Microbes · doi:10.1080/19490976.2017.1344809 · Cited by 101 · see citing works
TLR ligands and butyrate increasePyyexpression through two distinct but inter-regulated pathways
Larraufie, P., Dore, J. M., Lapaque, N., & Blottière, H. M. (2016) · Cellular Microbiology · doi:10.1111/cmi.12648 · Cited by 99 · see citing works
Fan, W., Huo, G., Li, X., Yang, L., & Duan, C. (2014) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.1309.09029 · Cited by 85 · see citing works
Ong, I. M., Gonzalez, J. G., McIlwain, S. J., Sawin, E. A., Schoen, A. J., Adluru, N., Alexander, A. L., & Yu, J.-P. J. (2018) · Translational Psychiatry · doi:10.1038/s41398-017-0022-5 · Cited by 83 · see citing works
Osadchiy, V., Labus, J. S., Gupta, A., Jacobs, J. P., Ashe-McNalley, C., Hsiao, E. Y., & Mayer, E. A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201772 · Cited by 76 · see citing works
Self-citationTingö, L., Kihlgren, A. L., Repsilber, D., Björkstén, B., Brummer, R. J., & Schoultz, I. (2015) · Nutrition Journal · doi:10.1186/s12937-016-0198-1 · Cited by 68 · see citing works
Rasmussen, M. K., Balaguer, P., Ekstrand, B., Daujat‐Chavanieu, M., & Gerbal‐Chaloin, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154629 · Cited by 67 · see citing works
Effects of Rifaximin on Central Responses to Social Stress—a Pilot Experiment
Wang, H., Braun, C., & Enck, P. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0627-2 · Cited by 23 · see citing works
Lambertsen, C. J., & Wright, W. B. (1973) · PubMed · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The microbiota-gut-brain axis: from motility to mood
Margolis, K. G., Cryan, J. F., & Mayer, E. A. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.066 · Cited by 999 · see citing works
Mayer, E. A., Nance, K., & Chen, S. (2022) · Annual Review of Medicine · doi:10.1146/annurev-med-042320-014032 · Cited by 813 · see citing works
Self-citationSex differences in gut microbiota
Kim, Y. S., Unno, T., Kim, B.-Y., & Park, M.-S. (2020) · The World Journal of Men s Health · doi:10.5534/wjmh.190009 · Cited by 610 · see citing works
Probiotics Regulate Gut Microbiota: An Effective Method to Improve Immunity
Wang, X., Zhang, P., & Zhang, X. (2021) · Molecules · doi:10.3390/molecules26196076 · Cited by 529 · see citing works
Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study
Zhang, B., Wang, H. E., Bai, Y.-M., Tsai, S.-J., Su, T.-P., Chen, T.-J., Wang, Y.-P., & Chen, M.-H. (2021) · Gut · doi:10.1136/gutjnl-2020-320789 · Cited by 292 · see citing works
Diseases, Disorders, and Comorbidities of Interoception
Bonaz, B., Lane, R. D., Oshinsky, M. L., Kenny, P. J., Sinha, R., Mayer, E. A., & Critchley, H. D. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.09.009 · Cited by 260 · see citing works
Self-citationLabanski, A., Langhorst, J., Engler, H., & Elsenbruch, S. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104501 · Cited by 200 · see citing works
Ge, L., Liu, S., Li, S., Yang, J., Hu, G., Xu, C., & Song, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1016578 · Cited by 187 · see citing works
Bhargava, A., Arnold, A. P., Bangasser, D. A., Denton, K. M., Gupta, A., Hilliard Krause, L. M., Mayer, E. A., McCarthy, M., Miller, W. L., Raznahan, A., et al. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnaa034 · Cited by 130 · see citing works
Self-citationBrain–Gut–Microbiome Interactions and Intermittent Fasting in Obesity
Frank, J., Gupta, A., Osadchiy, V., & Mayer, E. A. (2021) · Nutrients · doi:10.3390/nu13020584 · Cited by 68 · see citing works
Self-citationAntimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications
Caldara, M., & Marmiroli, N. (2021) · Pharmaceuticals · doi:10.3390/ph14090915 · Cited by 54 · see citing works
Gut Microbiome and Modulation of <scp>CNS</scp> Function
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Comprehensive Physiology · doi:10.1002/cphy.c180031 · Cited by 53 · see citing works
Self-citationHong, D., Zhang, C., Wu, W., Lu, X., & Zhang, L. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1133546 · Cited by 38 · see citing works
Zhang, B., Wang, H. E., Bai, Y., Tsai, S., Su, T., Chen, T., Wang, Y., & Chen, M. (2022) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15855 · Cited by 27 · see citing works
Wang, Z., Wang, X., Zhao, X., Hu, Z., Sun, D., Wu, D., & Xing, Y. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.970933 · Cited by 10 · see citing works
- Authors
- Osadchiy, V., Martin, C. R., & Mayer, E. A.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Mayer, Emeran A.
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 17
- Issue
- 2
- Pages
- 322-332
- ISSN
- 1542-3565 (ISSN-L)
- PMC
- PMC6999848
- OpenAlex
- W2895386130
- Cited by
- 555
- References
- 135
- Citations by year
- 2026: 59 · 2025: 85 · 2024: 98 · 2023: 95 · 2022: 97 · 2021: 70 · 2020: 35 · 2019: 14 · 2018: 2
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Gastroenterology and Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK048351, DK064539, DK096606)
- 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 › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- gut-brain axis, gut microbiota, two-way communication, intestinal permeability, blood-brain barrier, neuroinflammation, hormone signaling, developmental programming, diet, stress, food intake regulation, obesity, irritable bowel syndrome, therapeutic target
- MeSH terms
- Gastrointestinal Microbiome, Host Microbial Interactions, Biological Factors, Brain, Humans, Gastrointestinal Tract, 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
