Abstract
The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome.
Keywords
- Microbiota
- Gut-brain axis
- Immune system
- Metabolites
- Epigenetics
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Ader R, Kelley KW (2007) A global view of twenty years of brain, behavior, and immunity. Brain Behav Immun 21:20–22
Agans R, Rigsbee L, Kenche H, Michail S, Khamis HJ, Paliy O (2011) Distal gut microbiota of adolescent children is different from that of adults. FEMS Microbiol Ecol 77:404–412
Ait-Belgnaoui A, Durand H, Cartier C, Chaumaz G, Eutamene H, Ferrier L, Houdeau E, Fioramonti J, Bueno L, Theodorou V (2012) Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology 37:1885–1895
Al Akeel R (2013) Role of epigenetic reprogramming of host genes in bacterial pathogenesis. Saudi J Biol Sci 20:305–309
Alenghat T, Osborne LC, Saenz SA, Kobuley D, Ziegler CG, Mullican SE, Choi I, Grunberg S, Sinha R, Wynosky-Dolfi M, Snyder A, Giacomin PR, Joyce KL, Hoang TB, Bewtra M, Brodsky IE, Sonnenberg GF, Bushman FD, Won KJ, Lazar MA, Artis D (2013) Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature 504:153–157
Alonso C, Guilarte M, Vicario M, Ramos L, Ramadan Z, Antolin M, Martinez C, Rezzi S, Saperas E, Kochhar S, Santos J, Malagelada JR (2008) Maladaptive intestinal epithelial responses to life stress may predispose healthy women to gut mucosal inflammation. Gastroenterology 135:163–172.e161
Amaral FA, Sachs D, Costa VV, Fagundes CT, Cisalpino D, Cunha TM, Ferreira SH, Cunha FQ, Silva TA, Nicoli JR, Vieira LQ, Souza DG, Teixeira MM (2008) Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci U S A 105:2193–2197
Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, De Vos WM, Brunak S, Dore J, Meta HITC, Antolin M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, Van De Guchte M, Guedon E, Haimet F, Huber W, Van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Merieux A, Melo Minardi R, M’rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD, Bork P (2011) Enterotypes of the human gut microbiome. Nature 473:174–180
Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, Koga Y, Sudo N (2012) 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 303:G1288–G1295
Bajaj JS (2014) The role of microbiota in hepatic encephalopathy. Gut Microbes 5:397–403
Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, Monteith P, Noble NA, Sikaroodi M, Gillevet PM (2012) Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol 303:G675–G685
Bajaj JS, Heuman DM, Sanyal AJ, Hylemon PB, Sterling RK, Stravitz RT, Fuchs M, Ridlon JM, Daita K, Monteith P, Noble NA, White MB, Fisher A, Sikaroodi M, Rangwala H, Gillevet PM (2013) Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy. PLoS One 8:e60042
Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD (2008) MicroRNAs: new regulators of immune cell development and function. Nat Immunol 9:839–845
Bansal T, Alaniz RC, Wood TK, Jayaraman A (2010) The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci U S A 107:228–233
Barrett E, Ross RP, O’Toole PW, Fitzgerald GF, Stanton C (2012) γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113:411–417
Barry G, Mattick JS (2012) The role of regulatory RNA in cognitive evolution. Trends Cogn Sci 16:497–503
Bellezza I, Peirce MJ, Minelli A (2014) Cyclic dipeptides: from bugs to brain. Trends Mol Med 20:551–558
Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, Deng Y, Blennerhassett P, Macri J, Mccoy KD, Verdu EF, Collins SM (2011a) The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141:599–609, 609.e591–593
Bercik P, Park AJ, Sinclair D, Khoshdel A, Lu J, Huang X, Deng Y, Blennerhassett PA, Fahnestock M, Moine D, Berger B, Huizinga JD, Kunze W, Mclean PG, Bergonzelli GE, Collins SM, Verdu EF (2011b) The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil 23:1132–1139
Bierne H, Cossart P (2012) When bacteria target the nucleus: the emerging family of nucleomodulins. Cell Microbiol 14:622–633
Blaser MJ (2014) The microbiome revolution. J Clin Invest 124:4162–4165
Blaut M, Clavel T (2007) Metabolic diversity of the intestinal microbiota: implications for health and disease. J Nutr 137:751s–755s
Bohorquez DV, Shahid RA, Erdmann A, Kreger AM, Wang Y, Calakos N, Wang F, Liddle RA (2015) Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest 125(2):782–786
Bolca S, Van De Wiele T, Possemiers S (2013) Gut metabotypes govern health effects of dietary polyphenols. Curr Opin Biotechnol 24:220–225
Bone E, Tamm A, Hill M (1976) The production of urinary phenols by gut bacteria and their possible role in the causation of large bowel cancer. Am J Clin Nutr 29:1448–1454
Boontham P, Robins A, Chandran P, Pritchard D, Camara M, Williams P, Chuthapisith S, Mckechnie A, Rowlands BJ, Eremin O (2008) Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis. Clin Sci (Lond) 115:343–351
Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462
Borre YE, O’Keeffe GW, Clarke G, Stanton C, Dinan TG, Cryan JF (2014) Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med 20:509–518
Bourzac K (2014) Microbiome: the bacterial tightrope. Nature 516:S14–S16
Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF (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
Brucker RM, Bordenstein SR (2013) The capacious hologenome. Zoology (Jena) 116:260–261
Burcelin R, Cani PD, Knauf C (2007) Glucagon-like peptide-1 and energy homeostasis. J Nutr 137:2534s–2538s
Cabreiro F, Au C, Leung KY, Vergara-Irigaray N, Cocheme HM, Noori T, Weinkove D, Schuster E, Greene ND, Gems D (2013) Metformin retards aging in C. Elegans by altering microbial folate and methionine metabolism. Cell 153:228–239
Cahenzli J, Balmer ML, Mccoy KD (2013) Microbial-immune cross-talk and regulation of the immune system. Immunology 138:12–22
Calabresi P, Castrioto A, Di Filippo M, Picconi B (2013) New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson’s disease. Lancet Neurol 12:811–821
Cani PD (2013) Gut microbiota and obesity: lessons from the microbiome. Brief Funct Genomics 12:381–387
Cao X, Lin P, Jiang P, Li C (2013) Characteristics of the gastrointestinal microbiome in children with autism spectrum disorder: a systematic review. Shanghai Arch Psychiatry 25:342–353
Capuron L, Miller AH (2004) Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry 56:819–824
Cebra JJ (1999) Influences of microbiota on intestinal immune system development. Am J Clin Nutr 69:1046S–1051S
Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA (1999) Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid. J Biol Chem 274:21937–21942
Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HM, Coakley M, Lakshminarayanan B, O’Sullivan O, Fitzgerald GF, Deane J, O’Connor M, Harnedy N, O’Connor K, O’Mahony D, Van Sinderen D, Wallace M, Brennan L, Stanton C, Marchesi JR, Fitzgerald AP, Shanahan F, Hill C, Ross RP, O’Toole PW (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488:178–184
Clarke G, Cryan JF, Dinan TG, Quigley EM (2012) Review article: probiotics for the treatment of irritable bowel syndrome – focus on lactic acid bacteria. Aliment Pharmacol Ther 35(4):403–413
Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, Dinan TG, Cryan JF (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18:666–673
Claus SP, Tsang TM, Wang Y, Cloarec O, Skordi E, Martin FP, Rezzi S, Ross A, Kochhar S, Holmes E, Nicholson JK (2008) Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes. Mol Syst Biol 4:219
Collins LM, Toulouse A, Connor TJ, Nolan YM (2012) Contributions of central and systemic inflammation to the pathophysiology of Parkinson’s disease. Neuropharmacology 62:2154–2168
Coppen A, Shaw DM, Malleson A, Eccleston E, Gundy G (1965) Tryptamine metabolism in depression. Br J Psychiatry 111:993–998
Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, Almeida M, Quinquis B, Levenez F, Galleron N, Gougis S, Rizkalla S, Batto JM, Renault P, Dore J, Zucker JD, Clement K, Ehrlich SD (2013) Dietary intervention impact on gut microbial gene richness. Nature 500:585–588
Critchfield JW, Van Hemert S, Ash M, Mulder L, Ashwood P (2011) The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract 2011:161358
Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13:701–712
Cummings DE, Overduin J (2007) Gastrointestinal regulation of food intake. J Clin Invest 117:13–23
Da Silva WC, Bonini JS, Bevilaqua LR, Medina JH, Izquierdo I, Cammarota M (2008) Inhibition of mRNA synthesis in the hippocampus impairs consolidation and reconsolidation of spatial memory. Hippocampus 18:29–39
Daniel H, Moghaddas Gholami A, Berry D, Desmarchelier C, Hahne H, Loh G, Mondot S, Lepage P, Rothballer M, Walker A, Bohm C, Wenning M, Wagner M, Blaut M, Schmitt-Kopplin P, Kuster B, Haller D, Clavel T (2014) High-fat diet alters gut microbiota physiology in mice. ISME J 8:295–308
Das R, Kanungo MS (1979) Effects of Polyamines on Invitro Phosphorylation and Acetylation of Histones of the Cerebral-Cortex of Rats of Various Ages. Biochemical and Biophysical Research Communications. 90(3): p. 708–714
Davey KJ, Cotter PD, O’Sullivan O, Crispie F, Dinan TG, Cryan JF, O’Mahony SM (2013) Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl Psychiatry 3:e309
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–563
Dawson PA, Lan T, Rao A (2009) Bile acid transporters. J Lipid Res 50:2340–2357
De Theije CG, Wu J, Da Silva SL, Kamphuis PJ, Garssen J, Korte SM, Kraneveld AD (2011) Pathways underlying the gut-to-brain connection in autism spectrum disorders as future targets for disease management. Eur J Pharmacol 668(Suppl 1):S70–S80
De Theije CG, Wopereis H, Ramadan M, Van Eijndthoven T, Lambert J, Knol J, Garssen J, Kraneveld AD, Oozeer R (2014) Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behav Immun 37:197–206
De Vos WM, De Vos EA (2012) Role of the intestinal microbiome in health and disease: from correlation to causation. Nutr Rev 70(Suppl 1):S45–S56
De Vos WM, Nieuwdorp M (2013) Genomics: a gut prediction. Nature 498:48–49
De Weerth C, Fuentes S, Puylaert P, De Vos WM (2013) Intestinal microbiota of infants with colic: development and specific signatures. Pediatrics 131:e550–e558
Derkinderen P, Rouaud T, Lebouvier T, Bruley Des Varannes S, Neunlist M, De Giorgio R (2011) Parkinson disease: the enteric nervous system spills its guts. Neurology 77:1761–1767
Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG (2008) The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res 43:164–174
Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG (2010) Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 170:1179–1188
Desbonnet L, Clarke G, Shanahan F, Dinan TG, Cryan JF (2014) Microbiota is essential for social development in the mouse. Mol Psychiatry 19:146–148
Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, Hibberd ML, Forssberg H, Pettersson S (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 108:3047–3052
Dinan TG, Cryan J, Shanahan F, Keeling PW, Quigley EM (2010) IBS: An epigenetic perspective. Nat Rev Gastroenterol Hepatol 7(8):465–471
Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74:720–726
Douglas-Escobar M, Elliott E, Neu J (2013) Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr 167:374–379
Dror DK, Allen LH (2008) Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev 66:250–255
Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, Thomas G, Barbu V, Humbert L, Despras G, Bridonneau C, Dumetz F, Grill JP, Masliah J, Beaugerie L, Cosnes J, Chazouilleres O, Poupon R, Wolf C, Mallet JM, Langella P, Trugnan G, Sokol H, Seksik P (2013) Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 62:531–539
Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside J, Tatoud R, Blanc V, Lindon JC, Mitchell SC, Holmes E, Mccarthy MI, Scott J, Gauguier D, Nicholson JK (2006) Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci U S A 103:12511–12516
Duncan SH, Louis P, Thomson JM, Flint HJ (2009) The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol 11:2112–2122
Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308:1635–1638
El Aidy S, Kunze W, Bienenstock J, Kleerebezem M (2012a) The microbiota and the gut-brain axis: insights from the temporal and spatial mucosal alterations during colonisation of the germfree mouse intestine. Benef Microbes 3:251–259
El Aidy S, Van Baarlen P, Derrien M, Lindenbergh-Kortleve DJ, Hooiveld G, Levenez F, Dore J, Dekker J, Samsom JN, Nieuwenhuis EE, Kleerebezem M (2012b) Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice. Mucosal Immunol 5:567–579
El Aidy S, Derrien M, Merrifield CA, Levenez F, Dore J, Boekschoten MV, Dekker J, Holmes E, Zoetendal EG, Van Baarlen P, Claus SP, Kleerebezem M (2013a) Gut bacteria-host metabolic interplay during conventionalisation of the mouse germfree colon. ISME J 7:743–755
El Aidy S, Merrifield CA, Derrien M, Van Baarlen P, Hooiveld G, Levenez F, Dore J, Dekker J, Holmes E, Claus SP, Reijngoud DJ, Kleerebezem M (2013b) The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation. Gut 62:1306–1314
El Aidy S, Van Den Abbeele P, Van De Wiele T, Louis P, Kleerebezem M (2013c) Intestinal colonization: how key microbial players become established in this dynamic process: microbial metabolic activities and the interplay between the host and microbes. Bioessays 35:913–923
El Aidy S, Derrien M, Aardema R, Hooiveld G, Richards SE, Dane A, Dekker J, Vreeken R, Levenez F, Dore J, Zoetendal EG, Van Baarlen P, Kleerebezem M (2014a) Transient inflammatory-like state and microbial dysbiosis are pivotal in establishment of mucosal homeostasis during colonisation of germ-free mice. Benef Microbes 5:67–77
El Aidy S, Dinan TG, Cryan JF (2014b) Immune modulation of the brain-gut-microbe axis. Front Microbiol 5:146
El-Ansary AK, Ben Bacha A, Kotb M (2012) Etiology of autistic features: the persisting neurotoxic effects of propionic acid. J Neuroinflammation 9:74
Felger JC, Li L, Marvar PJ, Woolwine BJ, Harrison DG, Raison CL, Miller AH (2013) Tyrosine metabolism during interferon-alpha administration: association with fatigue and CSF dopamine concentrations. Brain Behav Immun 31:153–160
Ferland G (2012) Vitamin K, an emerging nutrient in brain function. Biofactors 38:151–157
Fischer A (2014) Epigenetic memory: the Lamarckian brain. EMBO J 33:945–967
Flint HJ, Scott KP, Louis P, Duncan SH (2012) The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol 9:577–589
Ford AC, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, Soffer EE, Spiegel BM, Moayyedi P (2014) Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 109:1547–1561; quiz 1546, 1562
Forsythe P, Kunze WA (2013) Voices from within: gut microbes and the CNS. Cell Mol Life Sci 70:55–69
Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J (2010) Mood and gut feelings. Brain Behav Immun 24:9–16
Fukuda S, Ohno H (2014) Gut microbiome and metabolic diseases. Semin Immunopathol 36:103–114
Funkhouser LJ, Bordenstein SR (2013) Mom knows best: the universality of maternal microbial transmission. PLoS Biol 11:e1001631
Furness JB, Rivera LR, Cho HJ, Bravo DM, Callaghan B (2013) The gut as a sensory organ. Nat Rev Gastroenterol Hepatol 10:729–740
Galindo-Villegas J, Garcia-Moreno D, De Oliveira S, Meseguer J, Mulero V (2012) Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development. Proc Natl Acad Sci U S A 109:E2605–E2614
Gareau MG, Jury J, Macqueen G, Sherman PM, Perdue MH (2007) Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut 56:1522–1528
Gareau MG, Wine E, Rodrigues DM, Cho JH, Whary MT, Philpott DJ, Macqueen G, Sherman PM (2011) Bacterial infection causes stress-induced memory dysfunction in mice. Gut 60:307–317
Gilbert SF, Mcdonald E, Boyle N, Buttino N, Gyi L, Mai M, Prakash N, Robinson J (2010) Symbiosis as a source of selectable epigenetic variation: taking the heat for the big guy. Philos Trans R Soc Lond B Biol Sci 365:671–678
Girvin GT, Stevenson JW (1954) Cell free choline acetylase from Lactobacillus plantarum. Can J Biochem Physiol 32:131–146
Gomez-Diaz E, Jorda M, Peinado MA, Rivero A (2012) Epigenetics of host-pathogen interactions: the road ahead and the road behind. PLoS Pathog 8:e1003007
Gondalia SV, Palombo EA, Knowles SR, Cox SB, Meyer D, Austin DW (2012) Molecular characterisation of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings. Autism Res 5:419–427
Gordon JI (2012) Honor thy gut symbionts redux. Science 336:1251–1253
Gorrindo P, Williams KC, Lee EB, Walker LS, Mcgrew SG, Levitt P (2012) Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res 5:101–108
Govindarajan N, Agis-Balboa RC, Walter J, Sananbenesi F, Fischer A (2011) Sodium butyrate improves memory function in an Alzheimer’s disease mouse model when administered at an advanced stage of disease progression. J Alzheimers Dis 26:187–197
Grafodatskaya D, Chung B, Szatmari P, Weksberg R (2010) Autism spectrum disorders and epigenetics. J Am Acad Child Adolesc Psychiatry 49:794–809
Grider JR, Piland BE (2007) The peristaltic reflex induced by short-chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF. Am J Physiol Gastrointest Liver Physiol 292:G429–G437
Gundersen BB, Blendy JA (2009) Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety. Neuropharmacology 57:67–74
Gupta VK, et al. (2013) Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner. Nat Neurosci. 16(10): p. 1453–60
Hall L, Kelley E (2014) The contribution of epigenetics to understanding genetic factors in autism. Autism 18:872–881
Hamon M, Blier P (2013) Monoamine neurocircuitry in depression and strategies for new treatments. Prog Neuropsychopharmacol Biol Psychiatry 45:54–63
Helsmoortel C, Vulto-Van Silfhout AT, Coe BP, Vandeweyer G, Rooms L, Van Den Ende J, Schuurs-Hoeijmakers JH, Marcelis CL, Willemsen MH, Vissers LE, Yntema HG, Bakshi M, Wilson M, Witherspoon KT, Malmgren H, Nordgren A, Anneren G, Fichera M, Bosco P, Romano C, De Vries BB, Kleefstra T, Kooy RF, Eichler EE, Van Der Aa N (2014) A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP. Nat Genet 46:380–384
Higuchi T, Hayashi H, Abe K (1997) Exchange of glutamate and gamma-aminobutyrate in a Lactobacillus strain. J Bacteriol 179:3362–3364
Hill MJ (1997) Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 6(Suppl 1):S43–S45
Holzer P, Farzi A (2014) Neuropeptides and the microbiota-gut-brain axis. Adv Exp Med Biol 817:195–219
Hooper LV, Littman DR, Macpherson AJ (2012) Interactions between the microbiota and the immune system. Science 336:1268–1273
Hosseini E, Grootaert C, Verstraete W, Van De Wiele T (2011) Propionate as a health-promoting microbial metabolite in the human gut. Nutr Rev 69:245–258
Hsiao EY, Mcbride SW, Hsien S, Sharon G, Hyde ER, Mccue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155:1451–1463
Human Microbiome Project Consortium (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214
Hyland NP, O’Mahony SM, O’Malley D, O’Mahony CM, Dinan TG, Cryan JF (2015) Early-life stress selectively affects gastrointestinal but not behavioral responses in a genetic model of brain-gut axis dysfunction. Neurogastroenterol Motil 27:105–113
Jasarevic E, Rodgers AB, Bale TL (2015) A novel role for maternal stress and microbial transmission in early life programming and neurodevelopment. Neurobiol Stress 1:81–88
Jimenez E, Delgado S, Maldonado A, Arroyo R, Albujar M, Garcia N, Jariod M, Fernandez L, Gomez A, Rodriguez JM (2008) Staphylococcus epidermidis: a differential trait of the fecal microbiota of breast-fed infants. BMC Microbiol 8:143
Jin J-S, Touyama M, Hisada T, Benno Y (2012) Effects of green tea consumption on human fecal microbiota with special reference to Bifidobacterium species. Microbiol Immunol 56(11):729–739
Johnson CL, Versalovic J (2012) The human microbiome and its potential importance to pediatrics. Pediatrics 129:950–960
Joyce SA, Macsharry J, Casey PG, Kinsella M, Murphy EF, Shanahan F, Hill C, Gahan CG (2014) Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proc Natl Acad Sci U S A 111:7421–7426
Kang DW, Park JG, Ilhan ZE, Wallstrom G, Labaer J, Adams JB, Krajmalnik-Brown R (2013) Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One 8:e68322
Karuri AR, Dobrowsky E, Tannock IF (1993) Selective cellular acidification and toxicity of weak organic acids in an acidic microenvironment. Br J Cancer 68:1080–1087
Keita AV, Soderholm JD, Ericson AC (2010) Stress-induced barrier disruption of rat follicle-associated epithelium involves corticotropin-releasing hormone, acetylcholine, substance P, and mast cells. Neurogastroenterol Motil 22:770–778, e221–e772
Kim JH (2014) Necrotizing enterocolitis: the road to zero. Semin Fetal Neonatal Med 19:39–44
Knights D, Ward TL, Mckinlay CE, Miller H, Gonzalez A, Mcdonald D, Knight R (2014) Rethinking “enterotypes”. Cell Host Microbe 16:433–437
Kobayashi K (2001) Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. J Investig Dermatol Symp Proc 6:115–121
Kumar H, Lund R, Laiho A, Lundelin K, Ley RE, Isolauri E, Salminen S (2014) Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis. MBio 5:e02113–e02114
Kundakovic M, Champagne FA (2015) Early-life experience, epigenetics, and the developing brain. Neuropsychopharmacology 40:141–153
Kunze WA, Furness JB (1999) The enteric nervous system and regulation of intestinal motility. Annu Rev Physiol 61:117–142
Lampron A, Elali A, Rivest S (2013) Innate immunity in the CNS: redefining the relationship between the CNS and its environment. Neuron 78:214–232
Landry CD, Kandel ER, Rajasethupathy P (2013) New mechanisms in memory storage: piRNAs and epigenetics. Trends Neurosci 36:535–542
Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jorgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clement K, Dore J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, De Vos WM, Zucker JD, Raes J, Hansen T, Meta HITC, Bork P, Wang J, Ehrlich SD, Pedersen O (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500:541–546
Leblanc JG, Milani C, De Giori GS, Sesma F, Van Sinderen D, Ventura M (2013) Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol 24:160–168
Lee JH, Lee J (2010) Indole as an intercellular signal in microbial communities. FEMS Microbiol Rev 34:426–444
Lemon KP, Armitage GC, Relman DA, Fischbach MA (2012) Microbiota-targeted therapies: an ecological perspective. Sci Transl Med 4:137rv5
Li Q, Korzan WJ, Ferrero DM, Chang RB, Roy DS, Buchi M, Lemon JK, Kaur AW, Stowers L, Fendt M, Liberles SD (2013) Synchronous evolution of an odor biosynthesis pathway and behavioral response. Curr Biol 23:11–20
Lievin-Le Moal V, Servin AL (2013) Pathogenesis of human enterovirulent bacteria: lessons from cultured, fully differentiated human colon cancer cell lines. Microbiol Mol Biol Rev 77:380–439
Lord, R. S., D. M. Tuttle and D. S. Cantor (2014). Adult bile acid amino transferase deficiency. Am J Case Rep 15:63–68
Louis P (2012) Does the human gut microbiota contribute to the etiology of autism spectrum disorders? Dig Dis Sci 57:1987–1989
Lowry CA, Hollis JH, De Vries A, Pan B, Brunet LR, Hunt JR, Paton JF, Van Kampen E, Knight DM, Evans AK, Rook GA, Lightman SL (2007) Identification of an immune-responsive mesolimbocortical serotonergic system: potential role in regulation of emotional behavior. Neuroscience 146:756–772
Lynn M (1991) Symbiogenesis and symbionticism. In: Lynn M, Rene F (eds) Symbiosis as a source of evolutionary innovation: speciation and morphogenesis. MIT, Cambridge
Lyte M (2011) Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. Bioessays 33:574–581
Lyte M, Cryan JF (2014) Microbial endocrinology: the microbiota-gut-brain axis in health and disease. Springer, New York
Lyte M, Freestone PP, Neal CP, Olson BA, Haigh RD, Bayston R, Williams PH (2003) Stimulation of Staphylococcus epidermidis growth and biofilm formation by catecholamine inotropes. Lancet 361:130–135
Macfabe DF (2012) Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microb Ecol Health Dis 23
Macfabe DF, Cain NE, Boon F, Ossenkopp KP, Cain DP (2011) Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: relevance to autism spectrum disorder. Behav Brain Res 217:47–54
Maes M, Kubera M, Leunis JC, Berk M (2012) Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J Affect Disord 141:55–62
Maestroni GJ (2000) Dendritic cell migration controlled by alpha 1b-adrenergic receptors. J Immunol 165:6743–6747
Magro F, Vieira-Coelho MA, Fraga S, Serrao MP, Veloso FT, Ribeiro T, Soares-Da-Silva P (2002) Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel disease. Dig Dis Sci 47:216–224
Mariat D, Firmesse O, Levenez F, Guimaraes V, Sokol H, Dore J, Corthier G, Furet JP (2009) The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9:123
Matsumoto M, Kibe R, Ooga T, Aiba Y, Sawaki E, Koga Y, Benno Y (2013) Cerebral low-molecular metabolites influenced by intestinal microbiota: a pilot study. Front Syst Neurosci 7:9
Mayer EA (2000) The neurobiology of stress and gastrointestinal disease. Gut 47:861–869
Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122:107–118
McKernan DP, Fitzgerald P, Dinan TG, Cryan JF (2010) The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat. Neurogastroenterol Motil 22:1029–e268
Mellios N, Sur M (2012) The emerging role of microRNAs in Schizophrenia and autism spectrum disorders. Front Psychiatry 3:39
Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR (2012) Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149:1635–1646
Minarovits J (2009) Microbe-induced epigenetic alterations in host cells: the coming era of patho-epigenetics of microbial infections. A review. Acta Microbiol Immunol Hung 56:1–19
Ming X, Stein TP, Barnes V, Rhodes N, Guo L (2012) Metabolic perturbance in autism spectrum disorders: a metabolomics study. J Proteome Res 11:5856–5862
Mitchell SC, Smith RL (2001) Trimethylaminuria: the fish malodor syndrome. Drug Metab Dispos 29:517–521
Miyake K, Hirasawa T, Koide T, Kubota T (2012) Epigenetics in autism and other neurodevelopmental diseases. Adv Exp Med Biol 724:91–98
Moffett JR, Namboodiri MA (2003) Tryptophan and the immune response. Immunol Cell Biol 81:247–265
Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW (2006) Central nervous system control of food intake and body weight. Nature 443:289–295
Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG (2015) The infant microbiome development: mom matters. Trends Mol Med 21(2):109–117
Mulle JG, Sharp WG, Cubells JF (2013) The gut microbiome: a new frontier in autism research. Curr Psychiatry Rep 15:337
Muller PA, Koscso B, Rajani GM, Stevanovic K, Berres ML, Hashimoto D, Mortha A, Leboeuf M, Li XM, Mucida D, Stanley ER, Dahan S, Margolis KG, Gershon MD, Merad M, Bogunovic M (2014) Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158:300–313
Musso G, Gambino R, Cassader M (2011) Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med 62:361–380
Neufeld KA, Kang N, Bienenstock J, Foster JA (2011) Effects of intestinal microbiota on anxiety-like behavior. Commun Integr Biol 4:492–494
Ng SY, Lin L, Soh BS, Stanton LW (2013) Long noncoding RNAs in development and disease of the central nervous system. Trends Genet 29:461–468
Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S (2012) Host-gut microbiota metabolic interactions. Science 336:1262–1267
Nielsen HB, Almeida M, Juncker AS, Rasmussen S, Li J, Sunagawa S, Plichta DR, Gautier L, Pedersen AG, Le Chatelier E, Pelletier E, Bonde I, Nielsen T, Manichanh C, Arumugam M, Batto JM, Quintanilha Dos Santos MB, Blom N, Borruel N, Burgdorf KS, Boumezbeur F, Casellas F, Dore J, Dworzynski P, Guarner F, Hansen T, Hildebrand F, Kaas RS, Kennedy S, Kristiansen K, Kultima JR, Leonard P, Levenez F, Lund O, Moumen B, Le Paslier D, Pons N, Pedersen O, Prifti E, Qin J, Raes J, Sorensen S, Tap J, Tims S, Ussery DW, Yamada T, Renault P, Sicheritz-Ponten T, Bork P, Wang J, Brunak S, Ehrlich SD (2014) Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat Biotechnol 32:822–828
Noack J, et al. (2000) The human gut bacteria Bacteroides thetaiotaomicron and Fusobacterium varium produce putrescine and spermidine in cecum of pectin-fed gnotobiotic rats. J Nutr. 130(5): p. 1225–31
Nohr MK, Pedersen MH, Gille A, Egerod KL, Engelstoft MS, Husted AS, Sichlau RM, Grunddal KV, Poulsen SS, Han S, Jones RM, Offermanns S, Schwartz TW (2013) 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 154:3552–3564
Nylund L, Satokari R, Salminen S, De Vos WM (2014) Intestinal microbiota during early life—impact on health and disease. Proc Nutr Soc 73:457–469
O’Connor RM, Dinan TG, Cryan JF (2012) Little things on which happiness depends: microRNAs as novel therapeutic targets for the treatment of anxiety and depression. Mol Psychiatry 17:359–376
O’Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EM, Cryan JF, Dinan TG (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65:263–267
O’Mahony SM, Felice VD, Nally K, Savignac HM, Claesson MJ, Scully P, Woznicki J, Hyland NP, Shanahan F, Quigley EM, Marchesi JR, O’Toole PW, Dinan TG, Cryan JF (2014) Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience 277:885–901
Ogilvie LA, Jones BV (2012) Dysbiosis modulates capacity for bile acid modification in the gut microbiomes of patients with inflammatory bowel disease: a mechanism and marker of disease? Gut 61:1642–1643
Okano-Matsumoto S, Mcroberts JA, Tache Y, Adelson DW (2011) Electrophysiological evidence for distinct vagal pathways mediating CCK-evoked motor effects in the proximal versus distal stomach. J Physiol 589:371–393
Olofsson PS, Rosas-Ballina M, Levine YA, Tracey KJ (2012) Rethinking inflammation: neural circuits in the regulation of immunity. Immunol Rev 248:188–204
Palmer C, Bik EM, Digiulio DB, Relman DA, Brown PO (2007) Development of the human infant intestinal microbiota. PLoS Biol 5:e177
Paschos K, Allday MJ (2010) Epigenetic reprogramming of host genes in viral and microbial pathogenesis. Trends Microbiol 18:439–447
Patterson AD, Turnbaugh PJ (2014) Microbial determinants of biochemical individuality and their impact on toxicology and pharmacology. Cell Metab 20:761–768
Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, Agis-Balboa RC, Cota P, Wittnam JL, Gogol-Doering A, Opitz L, Salinas-Riester G, Dettenhofer M, Kang H, Farinelli L, Chen W, Fischer A (2010) Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328:753–756
Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, Van Den Brandt PA, Stobberingh EE (2006) Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 118:511–521
Peregrin-Alvarez JM, Sanford C, Parkinson J (2009) The conservation and evolutionary modularity of metabolism. Genome Biol 10:R63
Peters B, Williams KC, Gorrindo P, Rosenberg D, Lee EB, Levitt P, Veenstra-Vanderweele J (2014) Rigid-compulsive behaviors are associated with mixed bowel symptoms in autism spectrum disorder. J Autism Dev Disord 44:1425–1432
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Meta HITC, Bork P, Ehrlich SD, Wang J (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65
Qureshi IA, Mehler MF (2012) Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease. Nat Rev Neurosci 13:528–541
Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70:31–41
Reardon C, Duncan GS, Brustle A, Brenner D, Tusche MW, Olofsson PS, Rosas-Ballina M, Tracey KJ, Mak TW (2013) Lymphocyte-derived ACh regulates local innate but not adaptive immunity. Proc Natl Acad Sci U S A 110:1410–1415
Reigstad CS, Salmonson CE, Rainey JF 3rd, Szurszewski JH, Linden DR, Sonnenburg JL, Farrugia G, Kashyap PC (2014) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29(4):1395–1403
Rhee SH, Pothoulakis C, Mayer EA (2009) Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol 6:306–314
Ridlon JM, Kang DJ, Hylemon PB (2006) Bile salt biotransformations by human intestinal bacteria. J Lipid Res 47:241–259
Robertson IH (2013) A noradrenergic theory of cognitive reserve: implications for Alzheimer’s disease. Neurobiol Aging 34:298–308
Rook GA (2013) Regulation of the immune system by biodiversity from the natural environment: an ecosystem service essential to health. Proc Natl Acad Sci U S A 110:18360–18367
Rosas-Ballina M, Olofsson PS, Ochani M, Valdes-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ (2011) Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334:98–101
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 JF, Ardid D, Desreumaux P (2007) Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med 13:35–37
Ruhl A, Collins SM (1997) Role of nitric oxide in norepinephrine release from myenteric plexus in vitro and in Trichinella spiralis-infected rats. Neurogastroenterol Motil 9:33–39
Saab BJ, Mansuy IM (2014) Neuroepigenetics of memory formation and impairment: the role of microRNAs. Neuropharmacology 80:61–69
Said HM, Mohammed ZM (2006) Intestinal absorption of water-soluble vitamins: an update. Curr Opin Gastroenterol 22:140–146
Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI (2008) 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 105:16767–16772
Santos J, Yang PC, Soderholm JD, Benjamin M, Perdue MH (2001) Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut 48:630–636
Santos F, Wegkamp A, De Vos WM, Smid EJ, Hugenholtz J (2008) High-level folate production in fermented foods by the B12 producer Lactobacillus reuteri JCM1112. Appl Environ Microbiol 74:3291–3294
Schaffer S, Halliwell B (2012) Do polyphenols enter the brain and does it matter? Some theoretical and practical considerations. Genes Nutr 7:99–109
Schanen NC (2006) Epigenetics of autism spectrum disorders. Hum Mol Genet 15(Spec No 2):R138–R150
Schaukowitch K, Kim TK (2014) Emerging epigenetic mechanisms of long non-coding RNAs. Neuroscience 264:25–38
Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P (2014) Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 30(3):350–358
Schor IE, Rascovan N, Pelisch F, Allo M, Kornblihtt AR (2009) Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proc Natl Acad Sci U S A 106:4325–4330
Schroeder FA, Lin CL, Crusio WE, Akbarian S (2007) Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry 62:55–64
Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C, Hardt PD (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18:190–195
Selkrig J, Wong P, Zhang X, Pettersson S (2014) Metabolic tinkering by the gut microbiome: implications for brain development and function. Gut Microbes 5:369–380
Shankar V, Agans R, Holmes B, Raymer M, Paliy O (2013) Do gut microbial communities differ in pediatric IBS and health? Gut Microbes 4:347–352
Sharon G, Segal D, Ringo JM, Hefetz A, Zilber-Rosenberg I, Rosenberg E (2010) Commensal bacteria play a role in mating preference of Drosophila melanogaster. Proc Natl Acad Sci U S A 107:20051–20056
Shaw W (2010) Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutr Neurosci 13:135–143
Shenderov BA, Midtvedt T (2014) Epigenomic programing: a future way to health? Microb Ecol Health Dis 25
Shishov VA, Kirovskaia TA, Kudrin VS, Oleskin AV (2009) Amine neuromediators, their precursors, and oxidation products in the culture of Escherichia coli K-12. Prikl Biokhim Mikrobiol 45:550–554
Siezen RJ, Kleerebezem M (2011) The human gut microbiome: are we our enterotypes? Microb Biotechnol 4:550–553
Silmon De Monerri NC, Kim K (2014) Pathogens hijack the epigenome: a new twist on host-pathogen interactions. Am J Pathol 184:897–911
Smith EA, Macfarlane GT (1997) Formation of phenolic and indolic compounds by Anaerobic bacteria in the human large intestine. Microb Ecol 33:180–188
Soliman ML, Combs CK, Rosenberger TA (2013) Modulation of inflammatory cytokines and mitogen-activated protein kinases by acetate in primary astrocytes. J Neuroimmune Pharmacol 8:287–300
Sridharan GV, Choi K, Klemashevich C, Wu C, Prabakaran D, Pan LB, Steinmeyer S, Mueller C, Yousofshahi M, Alaniz RC, Lee K, Jayaraman A (2014) Prediction and quantification of bioactive microbiota metabolites in the mouse gut. Nat Commun 5:5492
Stender JD, Glass CK (2013) Epigenomic control of the innate immune response. Curr Opin Pharmacol 13:582–587
Stilling RM, Fischer A (2011) The role of histone acetylation in age-associated memory impairment and Alzheimer’s disease. Neurobiol Learn Mem 96:19–26
Stilling RM, Bordenstein SR, Dinan TG, Cryan JF (2014a) Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? Front Cell Infect Microbiol 4:147
Stilling RM, Dinan TG, Cryan JF (2014b) Microbial genes, brain and behaviour—epigenetic regulation of the gut-brain axis. Genes Brain Behav 13:69–86
Straub RH, Wiest R, Strauch UG, Harle P, Scholmerich J (2006) The role of the sympathetic nervous system in intestinal inflammation. Gut 55:1640–1649
Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, Kubo C, Koga Y (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 558:263–275
Surana NK, Kasper DL (2014) Deciphering the tete-a-tete between the microbiota and the immune system. J Clin Invest 124:4197–4203
Swann JR, Want EJ, Geier FM, Spagou K, Wilson ID, Sidaway JE, Nicholson JK, Holmes E (2011) Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc Natl Acad Sci U S A 108(Suppl 1):4523–4530
Takaki M, Mawe GM, Barasch JM, Gershon MD, Gershon MD (1985) Physiological responses of guinea-pig myenteric neurons secondary to the release of endogenous serotonin by tryptamine. Neuroscience 16:223–240
Thomas RH, Meeking MM, Mepham JR, Tichenoff L, Possmayer F, Liu S, Macfabe DF (2012a) The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders. J Neuroinflammation 9:153
Thomas SP, Nandhra HS, Singh SP (2012b) Pharmacologic treatment of first-episode schizophrenia: a review of the literature. Prim Care Companion CNS Disord 14
Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff B, Mayer EA (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144:1394–1401, 1401.e1391–1394
Tran L, Chaloner A, Sawalha AH, Greenwood Van-Meerveld B (2013) Importance of epigenetic mechanisms in visceral pain induced by chronic water avoidance stress. Psychoneuroendocrinology 38(6):898–906
Tremaroli V, Backhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489:242–249
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031
Turvill JL, Connor P, Farthing MJ (2000) The inhibition of cholera toxin-induced 5-HT release by the 5-HT(3) receptor antagonist, granisetron, in the rat. Br J Pharmacol 130:1031–1036
Tzounis X, Vulevic J, Kuhnle GG, George T, Leonczak J, Gibson GR, Kwik-Uribe C, Spencer JP (2008) Flavanol monomer-induced changes to the human faecal microflora. Br J Nutr 99:782–792
Tzounis X, Rodriguez-Mateos A, Vulevic J, Gibson GR, Kwik-Uribe C, Spencer JP (2011) Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am J Clin Nutr 93:62–72
van de Vondervoort II, Gordebeke PM, Khoshab N, Tiesinga PH, Buitelaar JK, Kozicz T, Aschrafi A, Glennon JC (2013) Long non-coding RNAs in neurodevelopmental disorders. Front Mol Neurosci 6:53
Van Duynhoven J, Vaughan EE, Jacobs DM, Kemperman RA, Van Velzen EJ, Gross G, Roger LC, Possemiers S, Smilde AK, Dore J, Westerhuis JA, Van De Wiele T (2011) Metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci U S A 108(Suppl 1):4531–4538
Van Felius ID, Akkermans LM, Bosscha K, Verheem A, Harmsen W, Visser MR, Gooszen HG (2003) Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis. Neurogastroenterol Motil 15:267–276
Vavassori P, Mencarelli A, Renga B, Distrutti E, Fiorucci S (2009) The bile acid receptor FXR is a modulator of intestinal innate immunity. J Immunol 183:6251–6261
Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Despres S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T (2011) The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477:90–94
Walker WA (2013) Initial intestinal colonization in the human infant and immune homeostasis. Ann Nutr Metab 63(Suppl 2):8–15
Wall R, Cryan JF, Ross RP, Fitzgerald GF, Dinan TG, Stanton C (2014) Bacterial neuroactive compounds produced by psychobiotics. Adv Exp Med Biol 817:221–239
Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388
Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, Didonato JA, Lusis AJ, Hazen SL (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63
Weng NP, Araki Y, Subedi K (2012) The molecular basis of the memory T cell response: differential gene expression and its epigenetic regulation. Nat Rev Immunol 12:306–315
Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G (2009) Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A 106:3698–3703
Wilkinson B, Campbell DB (2013) Contribution of long noncoding RNAs to autism spectrum disorder risk. Int Rev Neurobiol 113:35–59
Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, Ishihara A, Kashyap PC, Fraser JS, Fischbach MA (2014) Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe 16:495–503
Woldemichael BT, Bohacek J, Gapp K, Mansuy IM (2014) Epigenetics of memory and plasticity. Prog Mol Biol Transl Sci 122:305–340
Wood NJ (2011) Microbiome: human gut microbiota can be readily cultured, manipulated and archived. Nat Rev Gastroenterol Hepatol 8:241
Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105–108
Young SN, Anderson GM, Gauthier S, Purdy WC (1980) The origin of indoleacetic acid and indolepropionic acid in rat and human cerebrospinal fluid. J Neurochem 34:1087–1092
Zapater P, Frances R, Gonzalez-Navajas JM, De La Hoz MA, Moreu R, Pascual S, Monfort D, Montoliu S, Vila C, Escudero A, Torras X, Cirera I, Llanos L, Guarner-Argente C, Palazon JM, Carnicer F, Bellot P, Guarner C, Planas R, Sola R, Serra MA, Munoz C, Perez-Mateo M, Such J (2008) Serum and ascitic fluid bacterial DNA: a new independent prognostic factor in noninfected patients with cirrhosis. Hepatology 48:1924–1931
Zareie M, Johnson-Henry K, Jury J, Yang PC, Ngan BY, Mckay DM, Soderholm JD, Perdue MH, Sherman PM (2006) Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut 55:1553–1560
Zhang H, Dibaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE, Krajmalnik-Brown R (2009) Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 106:2365–2370
Zheng X, Xie G, Zhao A, Zhao L, Yao C, Chiu NH, Zhou Z, Bao Y, Jia W, Nicholson JK, Jia W (2011) The footprints of gut microbial-mammalian co-metabolism. J Proteome Res 10:5512–5522
Ziats MN, Rennert OM (2013) Aberrant expression of long noncoding RNAs in autistic brain. J Mol Neurosci 49:589–593
Zijlmans MAC, Korpela K, Riksen-Walraven JM, De Vos WM, De Weerth C (2015) Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology 53:233–245
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El Aidy, S., Stilling, R., Dinan, T.G., Cryan, J.F. (2016). Microbiome to Brain: Unravelling the Multidirectional Axes of Communication. In: Lyte, M. (eds) Microbial Endocrinology: Interkingdom Signaling in Infectious Disease and Health. Advances in Experimental Medicine and Biology(), vol 874. Springer, Cham. https://doi.org/10.1007/978-3-319-20215-0_15
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DOI: https://doi.org/10.1007/978-3-319-20215-0_15
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