Abstract
Bacterial colonisation of the gut plays a major role in postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Individually, these systems have been implicated in the neuropathology of many CNS disorders and collectively they form an important bidirectional pathway of communication between the microbiota and the brain in health and disease. Regulation of the microbiome–brain–gut axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the CNS and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus, the concept of a microbiome–brain–gut axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.
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References
Adams JB et al (2011a) Gastrointestinal flora and gastrointestinal status in children with autism-comparisons to typical children and correlation with autism severity. BMC Gastroenterol 11:22
Adams JB et al (2011b) Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab (Lond) 8(1):34
Adlerberth I, Wold AE (2009) Establishment of the gut microbiota in Western infants. Acta Paediatr 98(2):229–238
Ait-Belgnaoui A et al (2012) Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology 37(11):1885–1895
Aroniadis OC, Brandt LJ (2013) Fecal microbiota transplantation: past, present and future. Curr Opin Gastroenterol 29(1):79–84
Arora T, Singh S, Sharma RK (2013) Probiotics: interaction with gut microbiome and antiobesity potential. Nutrition 29(4):591–596
Arumugam M et al (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174–180
Aziz Q, Thompson DG (1998) Brain–gut axis in health and disease. Gastroenterology 114(3):559–578
Backhed F et al (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101(44):15718–15723
Backhed F et al (2005) Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920
Backhed F et al (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104(3):979–984
Bailey MT, Coe CL (1999) Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev Psychobiol 35(2):146–155
Bailey MT et al (2011) Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun 25(3):397–407
Barrett E et al (2012a) Gamma-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113(2):411–417
Barrett E et al (2012b) Bifidobacterium breve with alpha-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome. PLoS One 7(11):e48159
Barrett E et al (2013) The individual-specific and diverse nature of the preterm infant microbiota. Arch Dis Child Fetal Neonatal Ed 98(4):F334–F340
Bateman A et al (1989) The immune-hypothalamic–pituitary–adrenal axis. Endocr Rev 10(1):92–112
Belzung C, Griebel G (2001) Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 125(1–2):141–149
Bengmark S (2013) Gut microbiota, immune development and function. Pharmacol Res 69(1):87–113
Benton D, Williams C, Brown A (2007) Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr 61(3):355–361
Bercik P (2011) The microbiota–gut–brain axis: learning from intestinal bacteria? Gut 60(3):288–289
Bercik P et al (2010) Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 139(6):2102–2112
Bercik P et al (2011a) The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141(2):599–609
Bercik P et al (2011b) The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil 23(12):1132–1139
Bested AC, Logan AC, Selhub EM (2013a) Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part I—autointoxication revisited. Gut Pathog 5(1):5
Bested AC, Logan AC, Selhub EM (2013b) Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III—convergence toward clinical trials. Gut Pathog 5(1):4
Bethea TC, Sikich L (2007) Early pharmacological treatment of autism: a rationale for developmental treatment. Biol Psychiatry 61(4):521–537
Biesiada G et al (2012) Lyme disease: review. Arch Med Sci 8(6):978–982
Bilbo SD, Schwarz JM (2012) The immune system and developmental programming of brain and behavior. Front Neuroendocrinol 33(3):267–286
Bonaz BL, Bernstein CN (2013) Brain–gut interactions in inflammatory bowel disease. Gastroenterology 144(1):36–49
Borody TJ, Khoruts A (2012) Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol 9(2):88–96
Bostrom AM et al (2012) Workplace aggression experienced by frontline staff in dementia care. J Clin Nurs 21(9–10):1453–1465
Bravo JA et al (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA 108(38):16050–16055
Bravo JA et al (2012) Communication between gastrointestinal bacteria and the nervous system. Curr Opin Pharmacol 12(6):667–672
Browne CA et al (2012) An effective dietary method for chronic tryptophan depletion in two mouse strains illuminates a role for 5-HT in nesting behaviour. Neuropharmacology 62(5–6):1903–1915
Caspi A et al (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386–389
Cho CE, Norman M (2013) Cesarean section and development of the immune system in the offspring. Am J Obstet Gynecol 208(4):249–254
Cho I et al (2012) Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488(7413):621–626
Claesson MJ et al (2011) Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA 108(Suppl 1):4586–4591
Claesson MJ et al (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488(7410):178–184
Clarke G et al (2009) Irritable bowel syndrome: towards biomarker identification. Trends Mol Med 15(10):478–489
Clarke G et al (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, Dinan TG, Cryan JF (2013a) Microbiome–gut–brain axis: encyclopedia of metagenomics. Springer, Berlin
Clarke G et al (2013b) The microbiome–gut–brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18(6):666–673
Codling C et al (2010) A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. Dig Dis Sci 55(2):392–397
Collins SM, Bercik P (2009) The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136(6):2003–2014
Collins SM, Bercik P (2013) Gut microbiota: Intestinal bacteria influence brain activity in healthy humans. Nat Rev Gastroenterol Hepatol 10(6):326–327
Collins SM, Surette M, Bercik P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10(11):735–742
Costedio MM, Hyman N, Mawe GM (2007) Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum 50(3):376–388
Costello EK et al (2012) The application of ecological theory toward an understanding of the human microbiome. Science 336(6086):1255–1262
Craft N, Li H (2013) Response to the commentaries on the paper: propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Investig Dermatol 133(9):2295–2297
Creed F et al (2003) The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology 124(2):303–317
Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13(10):701–712
Cryan JF, O’Mahony SM (2011) The microbiome–gut–brain axis: from bowel to behavior. Neurogastroenterol Motil 23(3):187–192
Damman CJ et al (2012) The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation? Am J Gastroenterol 107(10):1452–1459
Davari S et al (2013) Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: Behavioral and electrophysiological proofs for microbiome–gut–brain axis. Neuroscience 240:287–296
Davey KJ et al (2012) Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology (Berl) 221(1):155–169
Davey KJ et al (2013) Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl Psychiatry 3:e309
Davis KD et al (2008) Cortical thinning in IBS: implications for homeostatic, attention, and pain processing. Neurology 70(2):153–154
De Filippo C et al (2010) Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 107(33):14691–14696
de Theije CG et al (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
Deng W et al (2012) A mathematical model of mucilage expansion in myxospermous seeds of Capsella bursa-pastoris (shepherd’s purse). Ann Bot 109(2):419–427
Desbonnet L et al (2008) The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res 43(2):164–174
Desbonnet L et al (2010) Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 170(4):1179–1188
Desbonnet L et al (2013) Microbiota is essential for social development in the mouse. Mol Psychiatry. doi:10.1038/mp.2013.65
Diamond B et al (2011) It takes guts to grow a brain: increasing evidence of the important role of the intestinal microflora in neuro- and immune-modulatory functions during development and adulthood. Bioessays 33(8):588–591
Diaz Heijtz R et al (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA 108(7):3047–3052
Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74(10):720–726
Dominguez-Bello MG et al (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 107(26):11971–11975
Dooley W et al. (2011) Do the CMS proposed breast cancer quality measures actually predict improved outcomes? Am J Surg 202(6): 787–795; discussion 95
Douglas-Escobar M, Elliott E, Neu J (2013) Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr 167(4):374–379
Eckburg PB et al (2005) Diversity of the human intestinal microbial flora. Science 308(5728):1635–1638
Finegold SM et al (2002) Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 35(Suppl 1):S6–S16
Finegold SM et al (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16(4):444–453
Folks DG (2004) The interface of psychiatry and irritable bowel syndrome. Curr Psychiatry Rep 6(3):210–215
Fombonne E (2005) Epidemiology of autistic disorder and other pervasive developmental disorders. J Clin Psychiatry 66(Suppl 10):3–8
Forsythe P, Kunze WA (2013) Voices from within: gut microbes and the CNS. Cell Mol Life Sci 70(1):55–69
Forsythe P et al (2010) Mood and gut feelings. Brain Behav Immun 24(1):9–16
Foster JA, McVey Neufeld KA (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36(5):305–312
Fraher MH, O’Toole PW, Quigley EM (2012) Techniques used to characterize the gut microbiota: a guide for the clinician. Nat Rev Gastroenterol Hepatol 9(6):312–322
Garcia-Rodenas CL et al (2006) Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats. J Pediatr Gastroenterol Nutr 43(1):16–24
Gareau MG et al (2007) Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut 56(11):1522–1528
Gareau MG, Silva MA, Perdue MH (2008) Pathophysiological mechanisms of stress-induced intestinal damage. Curr Mol Med 8(4):274–281
Gareau MG et al (2011) Bacterial infection causes stress-induced memory dysfunction in mice. Gut 60(3):307–317
Genton L, Kudsk KA (2003) Interactions between the enteric nervous system and the immune system: role of neuropeptides and nutrition. Am J Surg 186(3):253–258
Ghosh S et al (2013) Fish oil attenuates omega-6 polyunsaturated fatty acid-induced dysbiosis and infectious colitis but impairs LPS dephosphorylation activity causing sepsis. PLoS One 8(2):e55468
Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125(6):1401–1412
Goehler LE et al (2005) Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun 19(4):334–344
Gondalia SV et al (2012) Molecular characterisation of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings. Autism Res 5(6):419–427
Grabrucker AM (2012) Environmental factors in autism. Front Psychiatry 3:118
Gregory KE (2011) Microbiome aspects of perinatal and neonatal health. J Perinat Neonatal Nurs 25(2): 158–162; quiz 63–64
Grenham S et al (2011) Brain–gut–microbe communication in health and disease. Front Physiol 2:94
Grice EA, Segre JA (2012) The human microbiome: our second genome. Annu Rev Genomics Hum Genet 13:151–170
Groeger D et al (2013) Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes 4(4):325–339
Gulati AS et al (2012) Mouse background strain profoundly influences Paneth cell function and intestinal microbial composition. PLoS One 7(2):e32403
Hakem A et al (2011) Role of Pirh2 in mediating the regulation of p53 and c-Myc. PLoS Genet 7(11):e1002360
Happe F et al (2006) Executive function deficits in autism spectrum disorders and attention-deficit/hyperactivity disorder: examining profiles across domains and ages. Brain Cogn 61(1):25–39
Hedges DW, Woon FL (2011) Early-life stress and cognitive outcome. Psychopharmacology (Berl) 214(1):121–130
Hillila MT, Farkkila NJ, Farkkila MA (2010) Societal costs for irritable bowel syndrome—a population based study. Scand J Gastroenterol 45(5):582–591
Holzer P, Reichmann F, Farzi A (2012) Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis. Neuropeptides 46(6):261–274
Hori T et al (1995) The autonomic nervous system as a communication channel between the brain and the immune system. Neuroimmunomodulation 2(4):203–215
Hornig M (2013) The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol 25(4):488–495
Jeffery IB et al (2012) An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 61(7):997–1006
Jimenez E et al (2008) Is meconium from healthy newborns actually sterile? Res Microbiol 159(3):187–193
Johnson CL, Versalovic J (2012) The human microbiome and its potential importance to pediatrics. Pediatrics 129(5):950–960
Johnson AC, Greenwood-Van Meerveld B, McRorie J (2011) Effects of Bifidobacterium infantis 35624 on post-inflammatory visceral hypersensitivity in the rat. Dig Dis Sci 56(11):3179–3186
Kandel E (2012) The biological mind and art. A conversation with Eric Kandel, MD. Interview by Sue Pondrom. Ann Neurol 72(5):A7–A8
Kasprowicz VO et al (2011) Diagnosing latent tuberculosis in high-risk individuals: rising to the challenge in high-burden areas. J Infect Dis 204(Suppl 4):S1168–S1178
Kendler KS, Thornton LM, Gardner CO (2000) Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the “kindling” hypothesis. Am J Psychiatry 157(8):1243–1251
Kennedy PJ et al (2012) Gut memories: towards a cognitive neurobiology of irritable bowel syndrome. Neurosci Biobehav Rev 36(1):310–340
Kinross J, Nicholson JK (2012) Gut microbiota: Dietary and social modulation of gut microbiota in the elderly. Nat Rev Gastroenterol Hepatol 9(10):563–564
Konieczna P et al (2012) Portrait of an immunoregulatory Bifidobacterium. Gut Microbes 3(3):261–266
Krogius-Kurikka L et al (2009) Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers. BMC Gastroenterol 9:95
Kunze WA et al (2009) Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J Cell Mol Med 13(8B):2261–2270
Larsen N et al (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5(2):e9085
Ledford JR, Gast DL (2006) Feeding problems in children with autism spectrum disorders : a review. Focus Autism Other Dev Disabl 21:153
Leonard BE (2005) The HPA and immune axes in stress: the involvement of the serotonergic system. Eur Psychiatry 20(Suppl 3):S302–S306
Ley RE et al (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102(31):11070–11075
Ley RE et al (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023
Longstreth GF et al (2006) Functional bowel disorders. Gastroenterology 130(5):1480–1491
Louis P (2012) Does the human gut microbiota contribute to the etiology of autism spectrum disorders? Dig Dis Sci 57(8):1987–1989
Lozupone CA et al (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489(7415):220–230
Lupien SJ et al (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10(6):434–445
Lyte M, Varcoe JJ, Bailey MT (1998) Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation. Physiol Behav 65(1):63–68
MacFabe DF et al (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(1):47–54
Macpherson AJ, Uhr T (2002) Gut flora—mechanisms of regulation. Eur J Surg Suppl 587:53–57
Maes M, Kubera M, Leunis JC (2008) The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett 29(1):117–124
Marco ML et al (2009) Lifestyle of Lactobacillus plantarum in the mouse caecum. Environ Microbiol 11(10):2747–2757
Marques TM et al (2010) Programming infant gut microbiota: influence of dietary and environmental factors. Curr Opin Biotechnol 21(2):149–156
Matsumoto M et al (2013) Cerebral low-molecular metabolites influenced by intestinal microbiota: a pilot study. Front Syst Neurosci 7:9
Matthews DM, Jenks SM (2013) Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice. Behav Processes 96:27–35
Mayer EA (2011) Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 12(8):453–466
Maynard CL et al (2012) Reciprocal interactions of the intestinal microbiota and immune system. Nature 489(7415):231–241
McEwen BS (2012) Brain on stress: how the social environment gets under the skin. Proc Natl Acad Sci USA 109(Suppl 2):17180–17185
McKernan DP et al (2010) The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat. Neurogastroenterol Motil 22 (9), 1029–1035, e268
McLean PG, Borman RA, Lee K (2007) 5-HT in the enteric nervous system: gut function and neuropharmacology. Trends Neurosci 30(1):9–13
McVey Neufeld KA et al (2013) The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol Motil 25(2):e88–e183
Mertz H (2002) Role of the brain and sensory pathways in gastrointestinal sensory disorders in humans. Gut 51(Suppl 1):i29–i33
Mertz H et al (2000) Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology 118(5):842–848
Messaoudi M et al (2011) Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2(4):256–261
Moayyedi P et al (2010) The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 59(3):325–332
Mocking RJ et al (2013) Relationship between the hypothalamic–pituitary–adrenal-axis and fatty acid metabolism in recurrent depression. Psychoneuroendocrinology 38(9):1607–1617
Moore P et al (2000) Clinical and physiological consequences of rapid tryptophan depletion. Neuropsychopharmacology 23(6):601–622
Mulle JG, Sharp WG, Cubells JF (2013) The gut microbiome: a new frontier in autism research. Curr Psychiatry Rep 15(2):337
Murphy EF et al (2013) Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut 62(2):220–226
Myint AM et al (2007) Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord 98(1–2):143–151
Myint AM et al (2013) Tryptophan metabolism and immunogenetics in major depression: a role for interferon-gamma gene. Brain Behav Immun 31:128–133
Nance DM, Sanders VM (2007) Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 21(6):736–745
Naslund J et al (2013) Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat. Psychopharmacology (Berl) 230(1):29–35
Neufeld KM et al (2011) Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 23(3): 255–264, e119
Nicholson JK et al (2012) Host-gut microbiota metabolic interactions. Science 336(6086):1262–1267
Nishino R et al (2013) Commensal microbiota modulate murine behaviors in a strictly contamination-free environment confirmed by culture-based methods. Neurogastroenterol Motil 25(6):521–528
Nolen-Hoeksema S, Larson J, Grayson C (1999) Explaining the gender difference in depressive symptoms. J Pers Soc Psychol 77(5):1061–1072
Nutt DJ, Malizia AL (2004) Structural and functional brain changes in posttraumatic stress disorder. J Clin Psychiatry 65(Suppl 1):11–17
Ohland CL et al (2013) Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology 38(9):1738–1747
Olivares M, Laparra JM, Sanz Y (2013) Host genotype, intestinal microbiota and inflammatory disorders. Br J Nutr 109(Suppl 2):S76–S80
O’Mahony SM et al (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65(3):263–267
O’Mahony SM et al (2011) Maternal separation as a model of brain–gut axis dysfunction. Psychopharmacology (Berl) 214(1):71–88
Ozawa E (1955) Studies on growth promotion by antibiotics. II. Results of aurofac administration to infants. J Antibiot (Tokyo) 8(6):212–214
Parfrey LW, Knight R (2012) Spatial and temporal variability of the human microbiota. Clin Microbiol Infect 18(Suppl 4):8–11
Parkes GC, Sanderson JD, Whelan K (2010) Treating irritable bowel syndrome with probiotics: the evidence. Proc Nutr Soc 69(2):187–194
Perez-Burgos A et al (2013) Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. Am J Physiol Gastrointest Liver Physiol 304(2):G211–G220
Pickett BE et al (2012) ViPR: an open bioinformatics database and analysis resource for virology research. Nucleic Acids Res 40(Database issue):D593–D598
Pimentel M, Lezcano S (2007) Irritable bowel syndrome: bacterial overgrowth—what’s known and what to do. Curr Treat Options Gastroenterol 10(4):328–337
Qin J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(7285):59–65
Qin J et al (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490(7418):55–60
Rabot S et al (2010) Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J 24(12):4948–4959
Rajilic-Stojanovic M, Smidt H, de Vos WM (2007) Diversity of the human gastrointestinal tract microbiota revisited. Environ Microbiol 9(9):2125–2136
Relman DA (2012) The human microbiome: ecosystem resilience and health. Nutr Rev 70(Suppl 1):S2–S9
Rhee SH, Pothoulakis C, Mayer EA (2009) Principles and clinical implications of the brain–gut–enteric microbiota axis. Nat Rev Gastroenterol Hepatol 6(5):306–314
Romero R, Korzeniewski SJ (2013) Are infants born by elective cesarean delivery without labor at risk for developing immune disorders later in life? Am J Obstet Gynecol 208(4):243–246
Rousseaux C et al (2007) Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med 13(1):35–37
Ruddick JP et al (2006) Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med 8(20):1–27
Salonen A, de Vos WM, Palva A (2010) Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives. Microbiology 156(Pt 11):3205–3215
Sam AH et al (2012) The role of the gut/brain axis in modulating food intake. Neuropharmacology 63(1):46–56
Sandler RH et al (2000) Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol 15(7):429–435
Saulnier DM et al (2013) The intestinal microbiome, probiotics and prebiotics in neurogastroenterology. Gut Microbes 4(1):17–27
Savignac HM et al (2013) Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine. Neurochem Int 63(8):756–764
Schellekens H et al (2012) Ghrelin signalling and obesity: at the interface of stress, mood and food reward. Pharmacol Ther 135(3):316–326
Schultz ST et al (2006) Breastfeeding, infant formula supplementation, and autistic disorder: the results of a parent survey. Int Breastfeed J 1:16
Scott LV, Clarke G, Dinan TG (2013) The brain–gut axis: a target for treating stress-related disorders. In: Halaris A, Leonard BE (eds) Inflammation in psychiatry, vol 28. Karger, Basel
Selye H (1936) A syndrome produced by diverse nocuous agents. 1936. J Neuropsychiatry Clin Neurosci 10(2):230–231
Sharp WG et al (2013) Feeding problems and nutrient intake in children with autism spectrum disorders: a meta-analysis and comprehensive review of the literature. J Autism Dev Disord 43(9):2159–2173
Smith AC et al (2012) Maternal gametic transmission of translocations or inversions of human chromosome 11p15.5 results in regional DNA hypermethylation and downregulation of CDKN1C expression. Genomics 99(1):25–35
Sonnenburg JL, Chen CT, Gordon JI (2006) Genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host. PLoS Biol 4(12):e413
Spiller R, Garsed K (2009) Postinfectious irritable bowel syndrome. Gastroenterology 136(6):1979–1988
Squire LR, Wixted JT (2011) The cognitive neuroscience of human memory since H.M. Annu Rev Neurosci 34:259–288
Squires H et al (2011) A systematic review and economic evaluation of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease. Health Technol Assess 15(40):1–210
Sudo N et al (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 558(Pt 1):263–275
Suzuki K et al (1983) Effects of crowding and heat stress on intestinal flora, body weight gain, and feed efficiency of growing rats and chicks. Nihon Juigaku Zasshi 45(3):331–338
Tack J et al (2006) A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut 55(8):1095–1103
Tana C et al (2010) Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 22(5): 512–519, e114–5
Tang WY, Ho SM (2007) Epigenetic reprogramming and imprinting in origins of disease. Rev Endocr Metab Disord 8(2):173–182
Tannock GW, Savage DC (1974) Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect Immun 9(3):591–598
Taylor MW, Feng GS (1991) Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J 5(11):2516–2522
Tillisch K et al (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144(7):1394–1401, 1401.e1–1401.e4
Timoveyev L et al (2002) Stability to sound stress and changeability in intestinal microflora. Eur Psychiatry 17(Suppl 1):200
Toorop PE et al (2012) Co-adaptation of seed dormancy and flowering time in the arable weed Capsella bursa-pastoris (shepherd’s purse). Ann Bot 109(2):481–489
Tremaroli V, Bäckhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489(7415):242–249
Turnbaugh PJ, Gordon JI (2009) The core gut microbiome, energy balance and obesity. J Physiol 587(Pt 17):4153–4158
Turnbaugh PJ et al (2009) A core gut microbiome in obese and lean twins. Nature 457(7228):480–484
Ursell LK et al (2012) The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites. J Allergy Clin Immunol 129(5):1204–1208
Vaishampayan PA et al (2010) Comparative metagenomics and population dynamics of the gut microbiota in mother and infant. Genome Biol Evol 2:53–66
Valles Y et al (2012) Metagenomics and development of the gut microbiota in infants. Clin Microbiol Infect 18(Suppl 4):21–26
Van Loo JA (2004) Prebiotics promote good health: the basis, the potential, and the emerging evidence. J Clin Gastroenterol 38(6 Suppl):S70–S75
van Nood E et al (2013) Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 368(5):407–415
Verdu EF et al (2006) Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut 55(2):182–190
Vighi G et al (2008) Allergy and the gastrointestinal system. Clin Exp Immunol 153(Suppl 1):3–6
Wall R et al (2010) Impact of administered bifidobacterium on murine host fatty acid composition. Lipids 45(5):429–436
Wall R et al (2012) Contrasting effects of Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 on the composition of murine brain fatty acids and gut microbiota. Am J Clin Nutr 95(5):1278–1287
Wang L et al (2012) Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig Dis Sci 57(8):2096–2102
Weberpals JI, Koti M, Squire JA (2011) Targeting genetic and epigenetic alterations in the treatment of serous ovarian cancer. Cancer Genet 204(10):525–535
Weilburg JB (2004) An overview of SSRI and SNRI therapies for depression. Manag Care 13(6 Suppl Depression):25–33
Williams BL et al (2011) Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One 6(9):e24585
Woods C, Squires M (2011) Health IT in New Jersey: a view from the New Jersey Health IT Coordinator’s office. MD Advis 4(4):18–21
Wrase J et al (2006) Serotonergic dysfunction: brain imaging and behavioral correlates. Cogn Affect Behav Neurosci 6(1):53–61
Zucchelli M et al (2011) Association of TNFSF15 polymorphism with irritable bowel syndrome. Gut 60(12):1671–1677
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Rachel D. Moloney and Lieve Desbonnet contributed equally to this study.
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Moloney, R.D., Desbonnet, L., Clarke, G. et al. The microbiome: stress, health and disease. Mamm Genome 25, 49–74 (2014). https://doi.org/10.1007/s00335-013-9488-5
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DOI: https://doi.org/10.1007/s00335-013-9488-5