The Brain-Gut-Microbiome Axis

Clair R Martin, Vadim Osadchiy, Amir Kalani, Emeran A Mayer, Clair R Martin, Vadim Osadchiy, Amir Kalani, Emeran A Mayer

Abstract

Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases.

Keywords: 2BA, secondary bile acid; 5-HT, serotonin; ANS, autonomic nervous system; ASD, autism spectrum disorder; BBB, blood-brain barrier; BGM, brain-gut-microbiome; CNS, central nervous system; ECC, enterochromaffin cell; EEC, enteroendocrine cell; FFAR, free fatty acid receptor; FGF, fibroblast growth factor; FXR, farnesoid X receptor; GF, germ-free; GI, gastrointestinal; GLP-1, glucagon-like peptide-1; GPR, G-protein–coupled receptor; IBS, irritable bowel syndrome; Intestinal Permeability; Irritable Bowel Syndrome; LPS, lipopolysaccharide; SCFA, short-chain fatty acid; SPF, specific-pathogen-free; Serotonin; Stress; TGR5, G protein-coupled bile acid receptor; Trp, tryptophan.

Figures

Figure 1
Figure 1
Bidirectional brain-gut-microbiome interactions related to serotonin signaling. Enterochromaffin cells (shown in green) contain more than 90% of the body’s serotonin (5-HT). 5-HT synthesis in ECCs is modulated by SCFAs and 2BAs produced by spore-forming Clostridiales, which increase their stimulatory actions on ECCs with increased dietary tryptophan availability. ECCs communicate with afferent nerve fibers through synapse-like connections between neuropod-like extensions and afferent nerve terminals. The autonomic nervous system can activate ECCs to release 5-HT into the gut lumen, where it can interact with gut microbes. TPH1, tryptophan hydroxylase type 1.
Figure 2
Figure 2
Systems biological model of brain-gut-microbiome interactions. The gut microbiota communicate with the gut connectome, the network of interacting cell types in the gut that include neuronal, glial, endocrine, and immune cells, via microbial metabolites, while changes in gut function can modulate gut microbial behavior. The brain connectome, the multiple interconnected structural networks of the central nervous system, generates and regulates autonomic nervous system influences that alter gut microbial composition and function indirectly by modulating the microbial environment in the gut. The gut microbiota can communicate to the brain indirectly via gut-derived molecules acting on afferent vagal and/or spinal nerve endings, or directly via microbe-generated signals. Alterations in the gain of these bidirectional interactions in response to perturbations such as psychosocial or gut-directed (eg, diet, medication, infection) stress can alter the stability and behavior of this system, manifesting as brain-gut disorders. Modified from Fung et al.

References

    1. Mayer E.A. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci. 2011;12:453–466.
    1. Rhee S.H., Pothoulakis C., Mayer E.A. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol. 2009;6:306–314.
    1. Cryan J.F., Dinan T.G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13:701–712.
    1. Park A.J., Collins J., Blennerhassett P.A., Ghia J.E., Verdu E.F., Bercik P., Collins S.M. Altered colonic function and microbiota profile in a mouse model of chronic depression. Neurogastroenterol Motil. 2013;25 733-e575.
    1. Vuong H.E., Hsiao E.Y. Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry. 2017;81:411–423.
    1. 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., Chesselet M.F., Keshavarzian A., Shannon K.M., Krajmalnik-Brown R., Wittung-Stafshede P., Knight R., Mazmanian S.K. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 2016;167:1469–1480 e12.
    1. Berer K., Mues M., Koutrolos M., Rasbi Z.A., Boziki M., Johner C., Wekerle H., Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479:538–541.
    1. Amaral F.A., Sachs D., Costa V.V., Fagundes C.T., Cisalpino D., Cunha T.M., Ferreira S.H., Cunha F.Q., Silva T.A., Nicoli J.R., Vieira L.Q., Souza D.G., Teixeira M.M. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci U S A. 2008;105:2193–2197.
    1. Bercik P., Denou E., Collins J., Jackson W., Lu J., Jury J., Deng Y., Blennerhassett P., Macri J., McCoy K.D., Verdu E.F., Collins S.M. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141:599–609. e1-3.
    1. Collins S.M., Kassam Z., Bercik P. The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Curr Opin Microbiol. 2013;16:240–245.
    1. 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., Young V.B., Henrissat B., Wilmes P., Stappenbeck T.S., Nunez G., Martens E.C. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167:1339–1353 e21.
    1. Bowey E., Adlercreutz H., Rowland I. Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats. Food Chem Toxicol. 2003;41:631–636.
    1. Mallett A.K., Bearne C.A., Rowland I.R., Farthing M.J., Cole C.B., Fuller R. The use of rats associated with a human faecal flora as a model for studying the effects of diet on the human gut microflora. J Appl Bacteriol. 1987;63:39–45.
    1. Bellono N.W., Bayrer J.R., Leitch D.B., Castro J., Zhang C., O'Donnell T.A., Brierley S.M., Ingraham H.A., Julius D. Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways. Cell. 2017;170:185–198 e16.
    1. Yissachar N., Zhou Y., Ung L., Lai N.Y., Mohan J.F., Ehrlicher A., Weitz D.A., Kasper D.L., Chiu I.M., Mathis D., Benoist C. An intestinal organ culture system uncovers a role for the nervous system in microbe-immune crosstalk. Cell. 2017;168:1135–1148 e12.
    1. Bravo J.A., Forsythe P., Chew M.V., Escaravage E., Savignac H.M., Dinan T.G., Bienenstock J., Cryan J.F. 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. 2011;108:16050–16055.
    1. Sudo N., Chida Y., Aiba Y., Sonoda J., Oyama N., Yu X.N., Kubo C., Koga Y. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558:263–275.
    1. Neufeld K.M., Kang N., Bienenstock J., Foster J.A. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011;23:255–264. e119.
    1. Diaz Heijtz R., Wang S., Anuar F., Qian Y., Bjorkholm B., Samuelsson A., Hibberd M.L., Forssberg H., Pettersson S. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011;108:3047–3052.
    1. Desbonnet L., Garrett L., Clarke G., Kiely B., Cryan J.F., Dinan T.G. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170:1179–1188.
    1. Clarke G., Grenham S., Scully P., Fitzgerald P., Moloney R.D., Shanahan F., Dinan T.G., Cryan J.F. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry. 2013;18:666–673.
    1. Bercik P., Park A.J., Sinclair D., Khoshdel A., Lu J., Huang X., Deng Y., Blennerhassett P.A., Fahnestock M., Moine D., Berger B., Huizinga J.D., Kunze W., McLean P.G., Bergonzelli G.E., Collins S.M., Verdu E.F. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil. 2011;23:1132–1139.
    1. Crumeyrolle-Arias M., Jaglin M., Bruneau A., Vancassel S., Cardona A., Dauge V., Naudon L., Rabot S. Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology. 2014;42:207–217.
    1. Savignac H.M., Kiely B., Dinan T.G., Cryan J.F. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil. 2014;26:1615–1627.
    1. De Palma G., Blennerhassett P., Lu J., Deng Y., Park A.J., Green W., Denou E., Silva M.A., Santacruz A., Sanz Y., Surette M.G., Verdu E.F., Collins S.M., Bercik P. Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nat Commun. 2015;6:7735.
    1. Hsiao E.Y., McBride S.W., Hsien S., Sharon G., Hyde E.R., McCue T., Codelli J.A., Chow J., Reisman S.E., Petrosino J.F., Patterson P.H., Mazmanian S.K. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–1463.
    1. Kelly J.R., Borre Y., C OB, Patterson E., El Aidy S., Deane J., Kennedy P.J., Beers S., Scott K., Moloney G., Hoban A.E., Scott L., Fitzgerald P., Ross P., Stanton C., Clarke G., Cryan J.F., Dinan T.G. Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016;82:109–118.
    1. Desbonnet L., Clarke G., Traplin A., O'Sullivan O., Crispie F., Moloney R.D., Cotter P.D., Dinan T.G., Cryan J.F. Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav Immun. 2015;48:165–173.
    1. Schroeder F.A., Lin C.L., Crusio W.E., Akbarian S. Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry. 2007;62:55–64.
    1. Desbonnet L., Garrett L., Clarke G., Bienenstock J., Dinan T.G. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43:164–174.
    1. Arseneault-Breard J., Rondeau I., Gilbert K., Girard S.A., Tompkins T.A., Godbout R., Rousseau G. Combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model. Br J Nutr. 2012;107:1793–1799.
    1. Zheng P., Zeng B., Zhou C., Liu M., Fang Z., Xu X., Zeng L., Chen J., Fan S., Du X., Zhang X., Yang D., Yang Y., Meng H., Li W., Melgiri N.D., Licinio J., Wei H., Xie P. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol Psychiatry. 2016;21:786–796.
    1. Ait-Belgnaoui A., Han W., Lamine F., Eutamene H., Fioramonti J., Bueno L., Theodorou V. Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction. Gut. 2006;55:1090–1094.
    1. Eutamene H., Lamine F., Chabo C., Theodorou V., Rochat F., Bergonzelli G.E., Corthesy-Theulaz I., Fioramonti J., Bueno L. Synergy between Lactobacillus paracasei and its bacterial products to counteract stress-induced gut permeability and sensitivity increase in rats. J Nutr. 2007;137:1901–1907.
    1. Rousseaux C., Thuru X., Gelot A., Barnich N., Neut C., Dubuquoy L., Dubuquoy C., Merour E., Geboes K., Chamaillard M., Ouwehand A., Leyer G., Carcano D., Colombel J.F., Ardid D., Desreumaux P. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med. 2007;13:35–37.
    1. Ma X., Mao Y.K., Wang B., Huizinga J.D., Bienenstock J., Kunze W. Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli. Am J Physiol Gastrointest Liver Physiol. 2009;296:G868–G875.
    1. Kunze W.A., Mao Y.K., Wang B., Huizinga J.D., Ma X., Forsythe P., Bienenstock J. Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J Cell Mol Med. 2009;13:2261–2270.
    1. Duca F.A., Swartz T.D., Sakar Y., Covasa M. Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota. PLoS One. 2012;7:e39748.
    1. 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. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328:228–231.
    1. Tanida M., Yamano T., Maeda K., Okumura N., Fukushima Y., Nagai K. Effects of intraduodenal injection of Lactobacillus johnsonii La1 on renal sympathetic nerve activity and blood pressure in urethane-anesthetized rats. Neurosci Lett. 2005;389:109–114.
    1. Mayer E.A., Tillisch K., Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125:926–938.
    1. Mayer E.A., Knight R., Mazmanian S.K., Cryan J.F., Tillisch K. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014;34:15490–15496.
    1. Bercik P., Collins S.M., Verdu E.F. Microbes and the gut-brain axis. Neurogastroenterol Motil. 2012;24:405–413.
    1. Martin C.R., Mayer E.A. Gut-brain axis and behavior. Nestle Nutr Inst Workshop Ser. 2017;88:45–53.
    1. Sharon G., Sampson T.R., Geschwind D.H., Mazmanian S.K. The central nervous system and the gut microbiome. Cell. 2016;167:915–932.
    1. Grill M.F., Maganti R.K. Neurotoxic effects associated with antibiotic use: management considerations. Br J Clin Pharmacol. 2011;72:381–393.
    1. Mohle L., Mattei D., Heimesaat M.M., Bereswill S., Fischer A., Alutis M., French T., Hambardzumyan D., Matzinger P., Dunay I.R., Wolf S.A. Ly6C(hi) monocytes provide a link between antibiotic-induced changes in gut microbiota and adult hippocampal neurogenesis. Cell Rep. 2016;15:1945–1956.
    1. Messaoudi M., Lalonde R., Violle N., Javelot H., Desor D., Nejdi A., Bisson J.F., Rougeot C., Pichelin M., Cazaubiel M., Cazaubiel J.M. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105:755–764.
    1. Kantak P.A., Bobrow D.N., Nyby J.G. Obsessive-compulsive-like behaviors in house mice are attenuated by a probiotic (Lactobacillus rhamnosus GG) Behav Pharmacol. 2014;25:71–79.
    1. D'Mello C., Ronaghan N., Zaheer R., Dicay M., Le T., MacNaughton W.K., Surrette M.G., Swain M.G. Probiotics improve inflammation-associated sickness behavior by altering communication between the peripheral immune system and the brain. J Neurosci. 2015;35:10821–10830.
    1. Cowan C.S., Callaghan B.L., Richardson R. The effects of a probiotic formulation (Lactobacillus rhamnosus and L. helveticus) on developmental trajectories of emotional learning in stressed infant rats. Transl Psychiatry. 2016;6:e823.
    1. 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., Biddinger S.B., Dutton R.J., Turnbaugh P.J. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–563.
    1. Carmody R.N., Gerber G.K., Luevano J.M., Jr., Gatti D.M., Somes L., Svenson K.L., Turnbaugh P.J. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe. 2015;17:72–84.
    1. Turnbaugh P.J., Ridaura V.K., Faith J.J., Rey F.E., Knight R., Gordon J.I. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1:6ra14.
    1. Li W., Dowd S.E., Scurlock B., Acosta-Martinez V., Lyte M. Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria. Physiol Behav. 2009;96:557–567.
    1. Jorgensen B.P., Hansen J.T., Krych L., Larsen C., Klein A.B., Nielsen D.S., Josefsen K., Hansen A.K., Sorensen D.B. A possible link between food and mood: dietary impact on gut microbiota and behavior in BALB/c mice. PLoS One. 2014;9:e103398.
    1. Beilharz J.E., Kaakoush N.O., Maniam J., Morris M.J. Cafeteria diet and probiotic therapy: cross talk among memory, neuroplasticity, serotonin receptors and gut microbiota in the rat. Mol Psychiatry. 2018;23:351–361.
    1. 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., Traynor J., Gregory C., De Palma G., Pigrau M., Ford A.C., Macri J., Berger B., Bergonzelli G., Surette M.G., Collins S.M., Moayyedi P., Bercik P. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153:448–459 e8.
    1. Tillisch K., Labus J., Kilpatrick L., Jiang Z., Stains J., Ebrat B., Guyonnet D., Legrain-Raspaud S., Trotin B., Naliboff B., Mayer E.A. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013;144:1394–1401. 401 e1-4.
    1. Steenbergen L., Sellaro R., van Hemert S., Bosch J.A., Colzato L.S. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015;48:258–264.
    1. Messaoudi M., Violle N., Bisson J.F., Desor D., Javelot H., Rougeot C. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes. 2011;2:256–261.
    1. Kelly J.R., Allen A.P., Temko A., Hutch W., Kennedy P.J., Farid N., Murphy E., Boylan G., Bienenstock J., Cryan J.F., Clarke G., Dinan T.G. Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun. 2017;61:50–59.
    1. Meyer C., Vassar M. The fragility of probiotic Bifidobacterium longum NCC3001 use for depression in patients with irritable bowel syndrome. Gastroenterology. 2018;154:764.
    1. McNulty N.P., Yatsunenko T., Hsiao A., Faith J.J., Muegge B.D., Goodman A.L., Henrissat B., Oozeer R., Cools-Portier S., Gobert G., Chervaux C., Knights D., Lozupone C.A., Knight R., Duncan A.E., Bain J.R., Muehlbauer M.J., Newgard C.B., Heath A.C., Gordon J.I. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci Transl Med. 2011;3:106ra106.
    1. Tolhurst G., Heffron H., Lam Y.S., Parker H.E., Habib A.M., Diakogiannaki E., Cameron J., Grosse J., Reimann F., Gribble F.M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61:364–371.
    1. Wang Y., Telesford K.M., Ochoa-Reparaz J., Haque-Begum S., Christy M., Kasper E.J., Wang L., Wu Y., Robson S.C., Kasper D.L., Kasper L.H. An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling. Nat Commun. 2014;5:4432.
    1. Singh V., Roth S., Llovera G., Sadler R., Garzetti D., Stecher B., Dichgans M., Liesz A. Microbiota dysbiosis controls the neuroinflammatory response after stroke. J Neurosci. 2016;36:7428–7440.
    1. 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. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–276.
    1. Wikoff W.R., Anfora A.T., Liu J., Schultz P.G., Lesley S.A., Peters E.C., Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A. 2009;106:3698–3703.
    1. 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., Gordon J.I. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008;105:16767–16772.
    1. Haghikia A., Jorg S., Duscha A., Berg J., Manzel A., Waschbisch A., Hammer A., Lee D.H., May C., Wilck N., Balogh A., Ostermann A.I., Schebb N.H., Akkad D.A., Grohme D.A., Kleinewietfeld M., Kempa S., Thone J., Demir S., Muller D.N., Gold R., Linker R.A. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity. 2015;43:817–829.
    1. Goehler L.E., Gaykema R.P., Opitz N., Reddaway R., Badr N., Lyte M. Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun. 2005;19:334–344.
    1. Barrett E., Ross R.P., O'Toole P.W., Fitzgerald G.F., Stanton C. gamma-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol. 2012;113:411–417.
    1. Minuk G.Y. Gamma-aminobutyric-acid (Gaba) production by 8 common bacterial pathogens. Scand J Infect Dis. 1986;18:465–467.
    1. Ozogul F. Effects of specific lactic acid bacteria species on biogenic amine production by foodborne pathogen. Int J Food Sci Tech. 2011;46:478–484.
    1. Shishov V.A., Kirovskaya T.A., Kudrin V.S., Oleskin A.V. Amine neuromediators, their precursors, and oxidation products in the culture of Escherichia coli K-12. Appl Biochem Micro. 2009;45:494–497.
    1. Asano Y., Hiramoto T., Nishino R., Aiba Y., Kimura T., Yoshihara K., Koga Y., Sudo N. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol. 2012;303:G1288–G1295.
    1. Furness J.B., Rivera L.R., Cho H.J., Bravo D.M., Callaghan B. The gut as a sensory organ. Nat Rev Gastroenterol Hepatol. 2013;10:729–740.
    1. Morton G.J., Kaiyala K.J., Foster-Schubert K.E., Cummings D.E., Schwartz M.W. Carbohydrate feeding dissociates the postprandial FGF19 response from circulating bile acid levels in humans. J Clin Endocrinol Metab. 2014;99:E241–E245.
    1. de Aguiar Vallim T.Q., Tarling E.J., Edwards P.A. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013;17:657–669.
    1. Wahlstrom A., Sayin S.I., Marschall H.U., Backhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016;24:41–50.
    1. Hsuchou H., Pan W., Kastin A.J. Fibroblast growth factor 19 entry into brain. Fluids Barriers CNS. 2013;10:32.
    1. Marcelin G., Jo Y.H., Li X., Schwartz G.J., Zhang Y., Dun N.J., Lyu R.M., Blouet C., Chang J.K., Chua S., Jr. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. Mol Metab. 2014;3:19–28.
    1. Tomlinson E., Fu L., John L., Hultgren B., Huang X., Renz M., Stephan J.P., Tsai S.P., Powell-Braxton L., French D., Stewart T.A. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity. Endocrinology. 2002;143:1741–1747.
    1. Fu L., John L.M., Adams S.H., Yu X.X., Tomlinson E., Renz M., Williams P.M., Soriano R., Corpuz R., Moffat B., Vandlen R., Simmons L., Foster J., Stephan J.P., Tsai S.P., Stewart T.A. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology. 2004;145:2594–2603.
    1. Ryan K.K., Kohli R., Gutierrez-Aguilar R., Gaitonde S.G., Woods S.C., Seeley R.J. Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats. Endocrinology. 2013;154:9–15.
    1. Perry R.J., Lee S., Ma L., Zhang D., Schlessinger J., Shulman G.I. FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nat Commun. 2015;6:6980.
    1. Maruyama T., Miyamoto Y., Nakamura T., Tamai Y., Okada H., Sugiyama E., Nakamura T., Itadani H., Tanaka K. Identification of membrane-type receptor for bile acids (M-BAR) Biochem Biophys Res Commun. 2002;298:714–719.
    1. Ridlon J.M., Kang D.J., Hylemon P.B. Bile salt biotransformations by human intestinal bacteria. J Lipid Res. 2006;47:241–259.
    1. Thomas C., Gioiello A., Noriega L., Strehle A., Oury J., Rizzo G., Macchiarulo A., Yamamoto H., Mataki C., Pruzanski M., Pellicciari R., Auwerx J., Schoonjans K. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10:167–177.
    1. Trabelsi M.S., Daoudi M., Prawitt J., Ducastel S., Touche V., Sayin S.I., Perino A., Brighton C.A., Sebti Y., Kluza J., Briand O., Dehondt H., Vallez E., Dorchies E., Baud G., Spinelli V., Hennuyer N., Caron S., Bantubungi K., Caiazzo R., Reimann F., Marchetti P., Lefebvre P., Backhed F., Gribble F.M., Schoonjans K., Pattou F., Tailleux A., Staels B., Lestavel S. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat Commun. 2015;6:7629.
    1. Topping D.L., Clifton P.M. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001;81:1031–1064.
    1. Russell W.R., Gratz S.W., Duncan S.H., Holtrop G., Ince J., Scobbie L., Duncan G., Johnstone A.M., Lobley G.E., Wallace R.J., Duthie G.G., Flint H.J. High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr. 2011;93:1062–1072.
    1. Cani P.D., Lecourt E., Dewulf E.M., Sohet F.M., Pachikian B.D., Naslain D., De Backer F., Neyrinck A.M., Delzenne N.M. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr. 2009;90:1236–1243.
    1. Nohr M.K., Egerod K.L., Christiansen S.H., Gille A., Offermanns S., Schwartz T.W., Moller M. Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia. Neuroscience. 2015;290:126–137.
    1. Kim D.Y., Camilleri M. Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol. 2000;95:2698–2709.
    1. Ruddick J.P., Evans A.K., Nutt D.J., Lightman S.L., Rook G.A., Lowry C.A. Tryptophan metabolism in the central nervous system: medical implications. Exp Rev Mol Med. 2006;8:1–27.
    1. Marin I.A., Goertz J.E., Ren T., Rich S.S., Onengut-Gumuscu S., Farber E., Wu M., Overall C.C., Kipnis J., Gaultier A. Microbiota alteration is associated with the development of stress-induced despair behavior. Sci Rep. 2017;7:43859.
    1. Fung T.C., Olson C.A., Hsiao E.Y. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20:145–155.
    1. Ochoa-Reparaz J., Mielcarz D.W., Ditrio L.E., Burroughs A.R., Begum-Haque S., Dasgupta S., Kasper D.L., Kasper L.H. Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J Immunol. 2010;185:4101–4108.
    1. Ochoa-Reparaz J., Mielcarz D.W., Ditrio L.E., Burroughs A.R., Foureau D.M., Haque-Begum S., Kasper L.H. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol. 2009;183:6041–6050.
    1. Benakis C., Brea D., Caballero S., Faraco G., Moore J., Murphy M., Sita G., Racchumi G., Ling L., Pamer E.G., Iadecola C., Anrather J. Commensal microbiota affects ischemic stroke outcome by regulating intestinal gammadelta T cells. Nat Med. 2016;22:516–523.
    1. Winek K., Engel O., Koduah P., Heimesaat M.M., Fischer A., Bereswill S., Dames C., Kershaw O., Gruber A.D., Curato C., Oyama N., Meisel C., Meisel A., Dirnagl U. Depletion of cultivatable gut microbiota by broad-spectrum antibiotic pretreatment worsens outcome after murine stroke. Stroke. 2016;47:1354–1363.
    1. Erny D., Hrabe de Angelis A.L., Jaitin D., Wieghofer P., Staszewski O., David E., Keren-Shaul H., Mahlakoiv T., Jakobshagen K., Buch T., Schwierzeck V., Utermohlen O., Chun E., Garrett W.S., McCoy K.D., Diefenbach A., Staeheli P., Stecher B., Amit I., Prinz M. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18:965–977.
    1. de Lartigue G., de La Serre C.B., Raybould H.E. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin. Physiol Behav. 2011;105:100–105.
    1. Barajon I., Serrao G., Arnaboldi F., Opizzi E., Ripamonti G., Balsari A., Rumio C. Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J Histochem Cytochem. 2009;57:1013–1023.
    1. Brun P., Giron M.C., Qesari M., Porzionato A., Caputi V., Zoppellaro C., Banzato S., Grillo A.R., Spagnol L., De Caro R., Pizzuti D., Barbieri V., Rosato A., Sturniolo G.C., Martines D., Zaninotto G., Palu G., Castagliuolo I. Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology. 2013;145:1323–1333.
    1. Mao Y.K., Kasper D.L., Wang B., Forsythe P., Bienenstock J., Kunze W.A. Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nat Commun. 2013;4:1465.
    1. Keita A.V., Soderholm J.D. The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterol Motil. 2010;22:718–733.
    1. Huang C., Wang J., Hu W., Wang C., Lu X., Tong L., Wu F., Zhang W. Identification of functional farnesoid X receptors in brain neurons. FEBS Lett. 2016;590:3233–3242.
    1. Keitel V., Gorg B., Bidmon H.J., Zemtsova I., Spomer L., Zilles K., Haussinger D. The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain. Glia. 2010;58:1794–1805.
    1. Kimura I., Inoue D., Maeda T., Hara T., Ichimura A., Miyauchi S., Kobayashi M., Hirasawa A., Tsujimoto G. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41) Proc Natl Acad Sci U S A. 2011;108:8030–8035.
    1. Won Y.J., Lu V.B., Puhl H.L., 3rd, Ikeda S.R. beta-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3. J Neurosci. 2013;33:19314–19325.
    1. Nohr M.K., Pedersen M.H., Gille A., Egerod K.L., Engelstoft M.S., Husted A.S., Sichlau R.M., Grunddal K.V., Poulsen S.S., Han S., Jones R.M., Offermanns S., Schwartz T.W. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology. 2013;154:3552–3564.
    1. Kelly J.R., Kennedy P.J., Cryan J.F., Dinan T.G., Clarke G., Hyland N.P. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015;9:392.
    1. 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., Tanoue T., Imaoka A., Itoh K., Takeda K., Umesaki Y., Honda K., Littman D.R. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139:485–498.
    1. Round J.L., Lee S.M., Li J., Tran G., Jabri B., Chatila T.A., Mazmanian S.K. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science. 2011;332:974–977.
    1. Kucharzik T., Lugering N., Rautenberg K., Lugering A., Schmidt M.A., Stoll R., Domschke W. Role of M cells in intestinal barrier function. Ann N Y Acad Sci. 2000;915:171–183.
    1. Vaishnava S., Behrendt C.L., Ismail A.S., Eckmann L., Hooper L.V. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl Acad Sci U S A. 2008;105:20858–20863.
    1. Hooper L.V., Wong M.H., Thelin A., Hansson L., Falk P.G., Gordon J.I. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001;291:881–884.
    1. Rakoff-Nahoum S., Paglino J., Eslami-Varzaneh F., Edberg S., Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229–241.
    1. Da Silva S., Robbe-Masselot C., Ait-Belgnaoui A., Mancuso A., Mercade-Loubiere M., Salvador-Cartier C., Gillet M., Ferrier L., Loubiere P., Dague E., Theodorou V., Mercier-Bonin M. Stress disrupts intestinal mucus barrier in rats via mucin O-glycosylation shift: prevention by a probiotic treatment. Am J Physiol Gastrointest Liver Physiol. 2014;307:G420–G429.
    1. Atuma C., Strugala V., Allen A., Holm L. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol Gastrointest Liver Physiol. 2001;280:G922–G929.
    1. Macfarlane S., Dillon J.F. Microbial biofilms in the human gastrointestinal tract. J Appl Microbiol. 2007;102:1187–1196.
    1. Johansson M.E., Larsson J.M., Hansson G.C. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4659–4665.
    1. Braniste V., Al-Asmakh M., Kowal C., Anuar F., Abbaspour A., Toth M., Korecka A., Bakocevic N., Ng L.G., Kundu P., Gulyas B., Halldin C., Hultenby K., Nilsson H., Hebert H., Volpe B.T., Diamond B., Pettersson S. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014;6:263ra158.
    1. 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., Pike N.B., Strum J.C., Steplewski K.M., Murdock P.R., Holder J.C., Marshall F.H., Szekeres P.G., Wilson S., Ignar D.M., Foord S.M., Wise A., Dowell S.J. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem. 2003;278:11312–11319.
    1. Michel L., Prat A. One more role for the gut: microbiota and blood brain barrier. Ann Transl Med. 2016;4:15.
    1. Varatharaj A., Galea I. The blood-brain barrier in systemic inflammation. Brain Behav Immun. 2017;60:1–12.
    1. Aguilera M., Vergara P., Martinez V. Stress and antibiotics alter luminal and wall-adhered microbiota and enhance the local expression of visceral sensory-related systems in mice. Neurogastroenterol Motil. 2013;25:e515–e529.
    1. Tannock G.W., Savage D.C. Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect Immun. 1974;9:591–598.
    1. Galley J.D., Nelson M.C., Yu Z.T., Dowd S.E., Walter J., Kumar P.S., Lyte M., Bailey M.T. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota. BMC Microbiol. 2014;14:189.
    1. Zijlmans M.A., Korpela K., Riksen-Walraven J.M., de Vos W.M., de Weerth C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology. 2015;53:233–245.
    1. Van Felius I.D., Akkermans L.M., Bosscha K., Verheem A., Harmsen W., Visser M.R., Gooszen H.G. Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis. Neurogastroenterol Motil. 2003;15:267–276.
    1. Lewis S.J., Heaton K.W. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32:920–924.
    1. Saad R.J., Rao S.S., Koch K.L., Kuo B., Parkman H.P., McCallum R.W., Sitrin M.D., Wilding G.E., Semler J.R., Chey W.D. Do stool form and frequency correlate with whole-gut and colonic transit? Results from a multicenter study in constipated individuals and healthy controls. Am J Gastroenterol. 2010;105:403–411.
    1. Vandeputte D., Falony G., Vieira-Silva S., Tito R.Y., Joossens M., Raes J. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut. 2016;65:57–62.
    1. Falony G., Joossens M., Vieira-Silva S., Wang J., Darzi Y., Faust K., Kurilshikov A., Bonder M.J., Valles-Colomer M., Vandeputte D., Tito R.Y., Chaffron S., Rymenans L., Verspecht C., De Sutter L., Lima-Mendez G., D'Hoe K., Jonckheere K., Homola D., Garcia R., Tigchelaar E.F., Eeckhaudt L., Fu J., Henckaerts L., Zhernakova A., Wijmenga C., Raes J. Population-level analysis of gut microbiome variation. Science. 2016;352:560–564.
    1. Roager H.M., Hansen L.B., Bahl M.I., Frandsen H.L., Carvalho V., Gobel R.J., Dalgaard M.D., Plichta D.R., Sparholt M.H., Vestergaard H., Hansen T., Sicheritz-Ponten T., Nielsen H.B., Pedersen O., Lauritzen L., Kristensen M., Gupta R., Licht T.R. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nat Microbiol. 2016;1:16093.
    1. Tottey W., Feria-Gervasio D., Gaci N., Laillet B., Pujos E., Martin J.F., Sebedio J.L., Sion B., Jarrige J.F., Alric M., Brugere J.F. Colonic transit time is a driven force of the gut microbiota composition and metabolism: in vitro evidence. J Neurogastroenterol Motil. 2017;23:124–134.
    1. Santos J., Yang P.C., Soderholm J.D., Benjamin M., Perdue M.H. Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut. 2001;48:630–636.
    1. Saunders P.R., Santos J., Hanssen N.P., Yates D., Groot J.A., Perdue M.H. Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH. Dig Dis Sci. 2002;47:208–215.
    1. Meddings J.B., Swain M.G. Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat. Gastroenterology. 2000;119:1019–1028.
    1. Demaude J., Salvador-Cartier C., Fioramonti J., Ferrier L., Bueno L. Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction. Gut. 2006;55:655–661.
    1. Lauffer A., Vanuytsel T., Vanormelingen C., Vanheel H., Salim Rasoel S., Toth J., Tack J., Fornari F., Farre R. Subacute stress and chronic stress interact to decrease intestinal barrier function in rats. Stress. 2016;19:225–234.
    1. Varghese A.K., Verdu E.F., Bercik P., Khan W.I., Blennerhassett P.A., Szechtman H., Collins S.M. Antidepressants attenuate increased susceptibility to colitis in a murine model of depression. Gastroenterology. 2006;130:1743–1753.
    1. Rubio C.A., Huang C.B. Quantification of the sulphomucin-producing cell population of the colonic mucosa during protracted stress in rats. In Vivo. 1992;6:81–84.
    1. Soderholm J.D., Yang P.C., Ceponis P., Vohra A., Riddell R., Sherman P.M., Perdue M.H. Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine. Gastroenterology. 2002;123:1099–1108.
    1. Houlden A., Goldrick M., Brough D., Vizi E.S., Lenart N., Martinecz B., Roberts I.S., Denes A. Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production. Brain Behav Immun. 2016;57:10–20.
    1. Kim Y.S., Ho S.B. Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep. 2010;12:319–330.
    1. Lyte M. The role of microbial endocrinology in infectious disease. J Endocrinol. 1993;137:343–345.
    1. Mayer E.A., Savidge T., Shulman R.J. Brain-gut microbiome interactions and functional bowel disorders. Gastroenterology. 2014;146:1500–1512.
    1. Santos J., Saperas E., Nogueiras C., Mourelle M., Antolin M., Cadahia A., Malagelada J.R. Release of mast cell mediators into the jejunum by cold pain stress in humans. Gastroenterology. 1998;114:640–648.
    1. Stephens R.L., Tache Y. Intracisternal injection of a TRH analogue stimulates gastric luminal serotonin release in rats. Am J Physiol. 1989;256:G377–G383.
    1. Yang H., Stephens R.L., Tache Y. TRH analogue microinjected into specific medullary nuclei stimulates gastric serotonin secretion in rats. Am J Physiol. 1992;262:G216–G222.
    1. Clarke M.B., Hughes D.T., Zhu C., Boedeker E.C., Sperandio V. The QseC sensor kinase: a bacterial adrenergic receptor. Proc Natl Acad Sci U S A. 2006;103:10420–10425.
    1. Lyte M. The role of catecholamines in gram-negative sepsis. Med Hypotheses. 1992;37:255–258.
    1. Alverdy J., Holbrook C., Rocha F., Seiden L., Wu R.L., Musch M., Chang E., Ohman D., Suh S. Gut-derived sepsis occurs when the right pathogen with the right virulence genes meets the right host: evidence for in vivo virulence expression in Pseudomonas aeruginosa. Ann Surg. 2000;232:480–489.
    1. Hughes D.T., Sperandio V. Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Microbiol. 2008;6:111–120.
    1. Cogan T.A., Thomas A.O., Rees L.E., Taylor A.H., Jepson M.A., Williams P.H., Ketley J., Humphrey T.J. Norepinephrine increases the pathogenic potential of Campylobacter jejuni. Gut. 2007;56:1060–1065.
    1. Paulose J.K., Wright J.M., Patel A.G., Cassone V.M. Human gut bacteria are sensitive to melatonin and express endogenous circadian rhythmicity. PLoS One. 2016;11:e0146643.
    1. Bubenik G.A., Brown G.M. Pinealectomy reduces melatonin levels in the serum but not in the gastrointestinal tract of rats. Biol Signals. 1997;6:40–44.
    1. Bubenik G.A., Pang S.F., Hacker R.R., Smith P.S. Melatonin concentrations in serum and tissues of porcine gastrointestinal tract and their relationship to the intake and passage of food. J Pineal Res. 1996;21:251–256.
    1. Thaiss C.A., Zeevi D., Levy M., Zilberman-Schapira G., Suez J., Tengeler A.C., Abramson L., Katz M.N., Korem T., Zmora N., Kuperman Y., Biton I., Gilad S., Harmelin A., Shapiro H., Halpern Z., Segal E., Elinav E. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014;159:514–529.
    1. Simren M., Barbara G., Flint H.J., Spiegel B.M., Spiller R.C., Vanner S., Verdu E.F., Whorwell P.J., Zoetendal E.G. Rome Foundation Committee. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013;62:159–176.
    1. Labus J.S., Hollister E.B., Jacobs J., Kirbach K., Oezguen N., Gupta A., Acosta J., Luna R.A., Aagaard K., Versalovic J., Savidge T., Hsiao E., Tillisch K., Mayer E.A. Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome. Microbiome. 2017;5:49.
    1. Jeffery I.B., O'Toole P.W., Ohman L., Claesson M.J., Deane J., Quigley E.M., Simren M. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2012;61:997–1006.
    1. Tap J., Derrien M., Tornblom H., Brazeilles R., Cools-Portier S., Dore J., Storsrud S., Le Neve B., Ohman L., Simren M. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017;152:111–123 e8.
    1. Kerckhoffs A.P., Ben-Amor K., Samsom M., van der Rest M.E., de Vogel J., Knol J., Akkermans L.M. Molecular analysis of faecal and duodenal samples reveals significantly higher prevalence and numbers of Pseudomonas aeruginosa in irritable bowel syndrome. J Med Microbiol. 2011;60:236–245.
    1. Pimentel M.F., Giamarellos-Bourboulis E.J., Pyleris E., Pistiki K., Tang J., Lee C., Harkins T., Kim G., Weitsman S., Barlow G.M., Chang C. The first large scale deep sequencing of the duodenal microbiome in irritable bowel syndrome reveals striking differences compared to healthy controls. Gastroenterology. 2013;144:S59.
    1. Bailey M.T., Dowd S.E., Galley J.D., Hufnagle A.R., Allen R.G., Lyte M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun. 2011;25:397–407.
    1. Knowles S.R., Nelson E.A., Palombo E.A. Investigating the role of perceived stress on bacterial flora activity and salivary cortisol secretion: a possible mechanism underlying susceptibility to illness. Biol Psychol. 2008;77:132–137.
    1. Pedram P., Wadden D., Amini P., Gulliver W., Randell E., Cahill F., Vasdev S., Goodridge A., Carter J.C., Zhai G., Ji Y., Sun G. Food addiction: its prevalence and significant association with obesity in the general population. PLoS One. 2013;8:e74832.
    1. Lin H.V., Frassetto A., Kowalik E.J., Jr., Nawrocki A.R., Lu M.M., Kosinski J.R., Hubert J.A., Szeto D., Yao X., Forrest G., Marsh D.J. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7:e35240.
    1. Everard A., Lazarevic V., Derrien M., Girard M., Muccioli G.G., Neyrinck A.M., Possemiers S., Van Holle A., Francois P., de Vos W.M., Delzenne N.M., Schrenzel J., Cani P.D. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes. 2011;60:2775–2786.
    1. Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R., Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031.
    1. Fernandez-Real J.M., Serino M., Blasco G., Puig J., Daunis-i-Estadella J., Ricart W., Burcelin R., Fernandez-Aranda F., Portero-Otin M. Gut microbiota interacts with brain microstructure and function. J Clin Endocrinol Metab. 2015;100:4505–4513.
    1. Janik R., Thomason L.A.M., Stanisz A.M., Forsythe P., Bienenstock J., Stanisz G.J. Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate. Neuroimage. 2016;125:988–995.
    1. Zhang H., DiBaise J.K., Zuccolo A., Kudrna D., Braidotti M., Yu Y., Parameswaran P., Crowell M.D., Wing R., Rittmann B.E., Krajmalnik-Brown R. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 2009;106:2365–2370.
    1. Li J.V., Ashrafian H., Bueter M., Kinross J., Sands C., le Roux C.W., Bloom S.R., Darzi A., Athanasiou T., Marchesi J.R., Nicholson J.K., Holmes E. Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk. Gut. 2011;60:1214–1223.
    1. Damms-Machado A., Mitra S., Schollenberger A.E., Kramer K.M., Meile T., Konigsrainer A., Huson D.H., Bischoff S.C. Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Biomed Res Int. 2015;2015:806248.
    1. Furet J.P., Kong L.C., Tap J., Poitou C., Basdevant A., Bouillot J.L., Mariat D., Corthier G., Dore J., Henegar C., Rizkalla S., Clement K. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–3057.
    1. Graessler J., Qin Y., Zhong H., Zhang J., Licinio J., Wong M.L., Xu A., Chavakis T., Bornstein A.B., Ehrhart-Bornstein M., Lamounier-Zepter V., Lohmann T., Wolf T., Bornstein S.R. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13:514–522.
    1. Liou A.P., Paziuk M., Luevano J.M., Jr., Machineni S., Turnbaugh P.J., Kaplan L.M. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5:178ra41.
    1. Tremaroli V., Karlsson F., Werling M., Stahlman M., Kovatcheva-Datchary P., Olbers T., Fandriks L., le Roux C.W., Nielsen J., Backhed F. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22:228–238.
    1. Kelly J.R., Clarke G., Cryan J.F., Dinan T.G. Brain-gut-microbiota axis: challenges for translation in psychiatry. Ann Epidemiol. 2016;26:366–372.
    1. Mertsalmi T.H., Aho V.T.E., Pereira P.A.B., Paulin L., Pekkonen E., Auvinen P., Scheperjans F. More than constipation - bowel symptoms in Parkinson's disease and their connection to gut microbiota. Eur J Neurol. 2017;24:1375–1383.
    1. Fasano A., Visanji N.P., Liu L.W.C., Lang A.E., Pfeiffer R.F. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol. 2015;14:625–639.
    1. Mayer E.A., Padua D., Tillisch K. Altered brain-gut axis in autism: comorbidity or causative mechanisms? Bioessays. 2014;36:933–939.
    1. Kang D.W., Adams J.B., Gregory A.C., Borody T., Chittick L., Fasano A., Khoruts A., Geis E., Maldonado J., McDonough-Means S., Pollard E.L., Roux S., Sadowsky M.J., Lipson K.S., Sullivan M.B., Caporaso J.G., Krajmalnik-Brown R. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017;5:10.
    1. Mayer E.A., Labus J.S., Tillisch K., Cole S.W., Baldi P. Towards a systems view of IBS. Nat Rev Gastroenterol Hepatol. 2015;12:592–605.
    1. Bohorquez D.V., Liddle R.A. The gut connectome: making sense of what you eat. J Clin Invest. 2015;125:888–890.
    1. Sporns O. The human connectome: origins and challenges. Neuroimage. 2013;80:53–61.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다