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Mammalian Genome

, Volume 25, Issue 1–2, pp 49–74 | Cite as

The microbiome: stress, health and disease

  • Rachel D. Moloney
  • Lieve Desbonnet
  • Gerard Clarke
  • Timothy G. Dinan
  • John F. Cryan
Article

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.

Keywords

Autism Spectrum Disorder Autism Spectrum Disorder Irritable Bowel Syndrome Enteric Nervous System Irritable Bowel Syndrome Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 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 11:22PubMedCentralPubMedGoogle Scholar
  2. 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):34PubMedCentralGoogle Scholar
  3. Adlerberth I, Wold AE (2009) Establishment of the gut microbiota in Western infants. Acta Paediatr 98(2):229–238PubMedGoogle Scholar
  4. 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):1885–1895PubMedGoogle Scholar
  5. Aroniadis OC, Brandt LJ (2013) Fecal microbiota transplantation: past, present and future. Curr Opin Gastroenterol 29(1):79–84PubMedGoogle Scholar
  6. Arora T, Singh S, Sharma RK (2013) Probiotics: interaction with gut microbiome and antiobesity potential. Nutrition 29(4):591–596PubMedGoogle Scholar
  7. Arumugam M et al (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174–180PubMedCentralPubMedGoogle Scholar
  8. Aziz Q, Thompson DG (1998) Brain–gut axis in health and disease. Gastroenterology 114(3):559–578PubMedGoogle Scholar
  9. Backhed F et al (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101(44):15718–15723PubMedGoogle Scholar
  10. Backhed F et al (2005) Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920PubMedGoogle Scholar
  11. Backhed F et al (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104(3):979–984PubMedGoogle Scholar
  12. Bailey MT, Coe CL (1999) Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev Psychobiol 35(2):146–155PubMedGoogle Scholar
  13. 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):397–407PubMedCentralPubMedGoogle Scholar
  14. Barrett E et al (2012a) Gamma-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113(2):411–417PubMedGoogle Scholar
  15. 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):e48159PubMedCentralPubMedGoogle Scholar
  16. 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–F340PubMedGoogle Scholar
  17. Bateman A et al (1989) The immune-hypothalamic–pituitary–adrenal axis. Endocr Rev 10(1):92–112PubMedGoogle Scholar
  18. Belzung C, Griebel G (2001) Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 125(1–2):141–149PubMedGoogle Scholar
  19. Bengmark S (2013) Gut microbiota, immune development and function. Pharmacol Res 69(1):87–113PubMedGoogle Scholar
  20. 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):355–361Google Scholar
  21. Bercik P (2011) The microbiota–gut–brain axis: learning from intestinal bacteria? Gut 60(3):288–289PubMedGoogle Scholar
  22. Bercik P et al (2010) Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 139(6):2102–2112PubMedGoogle Scholar
  23. Bercik P et al (2011a) The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141(2):599–609PubMedGoogle Scholar
  24. Bercik P et al (2011b) The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil 23(12):1132–1139PubMedCentralPubMedGoogle Scholar
  25. 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):5PubMedCentralPubMedGoogle Scholar
  26. 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):4PubMedCentralPubMedGoogle Scholar
  27. Bethea TC, Sikich L (2007) Early pharmacological treatment of autism: a rationale for developmental treatment. Biol Psychiatry 61(4):521–537PubMedCentralPubMedGoogle Scholar
  28. Biesiada G et al (2012) Lyme disease: review. Arch Med Sci 8(6):978–982PubMedCentralPubMedGoogle Scholar
  29. Bilbo SD, Schwarz JM (2012) The immune system and developmental programming of brain and behavior. Front Neuroendocrinol 33(3):267–286PubMedCentralPubMedGoogle Scholar
  30. Bonaz BL, Bernstein CN (2013) Brain–gut interactions in inflammatory bowel disease. Gastroenterology 144(1):36–49PubMedGoogle Scholar
  31. Borody TJ, Khoruts A (2012) Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol 9(2):88–96Google Scholar
  32. Bostrom AM et al (2012) Workplace aggression experienced by frontline staff in dementia care. J Clin Nurs 21(9–10):1453–1465PubMedGoogle Scholar
  33. 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):16050–16055PubMedGoogle Scholar
  34. Bravo JA et al (2012) Communication between gastrointestinal bacteria and the nervous system. Curr Opin Pharmacol 12(6):667–672PubMedGoogle Scholar
  35. 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):1903–1915PubMedGoogle Scholar
  36. Caspi A et al (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386–389PubMedGoogle Scholar
  37. Cho CE, Norman M (2013) Cesarean section and development of the immune system in the offspring. Am J Obstet Gynecol 208(4):249–254PubMedGoogle Scholar
  38. Cho I et al (2012) Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488(7413):621–626PubMedCentralPubMedGoogle Scholar
  39. 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):4586–4591PubMedGoogle Scholar
  40. Claesson MJ et al (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488(7410):178–184PubMedGoogle Scholar
  41. Clarke G et al (2009) Irritable bowel syndrome: towards biomarker identification. Trends Mol Med 15(10):478–489PubMedGoogle Scholar
  42. 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):403–413PubMedGoogle Scholar
  43. Clarke G, Dinan TG, Cryan JF (2013a) Microbiome–gut–brain axis: encyclopedia of metagenomics. Springer, BerlinGoogle Scholar
  44. 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):666–673PubMedGoogle Scholar
  45. Codling C et al (2010) A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. Dig Dis Sci 55(2):392–397PubMedGoogle Scholar
  46. Collins SM, Bercik P (2009) The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136(6):2003–2014PubMedGoogle Scholar
  47. Collins SM, Bercik P (2013) Gut microbiota: Intestinal bacteria influence brain activity in healthy humans. Nat Rev Gastroenterol Hepatol 10(6):326–327PubMedGoogle Scholar
  48. Collins SM, Surette M, Bercik P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10(11):735–742PubMedGoogle Scholar
  49. Costedio MM, Hyman N, Mawe GM (2007) Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum 50(3):376–388PubMedGoogle Scholar
  50. Costello EK et al (2012) The application of ecological theory toward an understanding of the human microbiome. Science 336(6086):1255–1262PubMedGoogle Scholar
  51. 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):2295–2297PubMedGoogle Scholar
  52. Creed F et al (2003) The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology 124(2):303–317PubMedGoogle Scholar
  53. Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13(10):701–712PubMedGoogle Scholar
  54. Cryan JF, O’Mahony SM (2011) The microbiome–gut–brain axis: from bowel to behavior. Neurogastroenterol Motil 23(3):187–192PubMedGoogle Scholar
  55. 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):1452–1459PubMedGoogle Scholar
  56. 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 240:287–296PubMedGoogle Scholar
  57. 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):155–169Google Scholar
  58. 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:e309PubMedCentralPubMedGoogle Scholar
  59. Davis KD et al (2008) Cortical thinning in IBS: implications for homeostatic, attention, and pain processing. Neurology 70(2):153–154PubMedGoogle Scholar
  60. 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):14691–14696PubMedGoogle Scholar
  61. 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–S80PubMedGoogle Scholar
  62. 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):419–427PubMedGoogle Scholar
  63. Desbonnet L et al (2008) The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res 43(2):164–174PubMedGoogle Scholar
  64. Desbonnet L et al (2010) Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 170(4):1179–1188PubMedGoogle Scholar
  65. Desbonnet L et al (2013) Microbiota is essential for social development in the mouse. Mol Psychiatry. doi: 10.1038/mp.2013.65
  66. 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):588–591PubMedGoogle Scholar
  67. Diaz Heijtz R et al (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA 108(7):3047–3052PubMedGoogle Scholar
  68. Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74(10):720–726PubMedGoogle Scholar
  69. 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):11971–11975PubMedGoogle Scholar
  70. 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 95Google Scholar
  71. Douglas-Escobar M, Elliott E, Neu J (2013) Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr 167(4):374–379PubMedGoogle Scholar
  72. Eckburg PB et al (2005) Diversity of the human intestinal microbial flora. Science 308(5728):1635–1638PubMedCentralPubMedGoogle Scholar
  73. Finegold SM et al (2002) Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 35(Suppl 1):S6–S16PubMedGoogle Scholar
  74. Finegold SM et al (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16(4):444–453PubMedGoogle Scholar
  75. Folks DG (2004) The interface of psychiatry and irritable bowel syndrome. Curr Psychiatry Rep 6(3):210–215PubMedGoogle Scholar
  76. Fombonne E (2005) Epidemiology of autistic disorder and other pervasive developmental disorders. J Clin Psychiatry 66(Suppl 10):3–8PubMedGoogle Scholar
  77. Forsythe P, Kunze WA (2013) Voices from within: gut microbes and the CNS. Cell Mol Life Sci 70(1):55–69PubMedGoogle Scholar
  78. Forsythe P et al (2010) Mood and gut feelings. Brain Behav Immun 24(1):9–16PubMedGoogle Scholar
  79. Foster JA, McVey Neufeld KA (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36(5):305–312PubMedGoogle Scholar
  80. 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):312–322PubMedGoogle Scholar
  81. 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):16–24PubMedGoogle Scholar
  82. Gareau MG et al (2007) Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut 56(11):1522–1528PubMedGoogle Scholar
  83. Gareau MG, Silva MA, Perdue MH (2008) Pathophysiological mechanisms of stress-induced intestinal damage. Curr Mol Med 8(4):274–281PubMedGoogle Scholar
  84. Gareau MG et al (2011) Bacterial infection causes stress-induced memory dysfunction in mice. Gut 60(3):307–317PubMedGoogle Scholar
  85. 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):253–258PubMedGoogle Scholar
  86. 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):e55468PubMedCentralPubMedGoogle Scholar
  87. Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125(6):1401–1412PubMedGoogle Scholar
  88. 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):334–344PubMedGoogle Scholar
  89. 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):419–427PubMedGoogle Scholar
  90. Grabrucker AM (2012) Environmental factors in autism. Front Psychiatry 3:118PubMedCentralPubMedGoogle Scholar
  91. Gregory KE (2011) Microbiome aspects of perinatal and neonatal health. J Perinat Neonatal Nurs 25(2): 158–162; quiz 63–64Google Scholar
  92. Grenham S et al (2011) Brain–gut–microbe communication in health and disease. Front Physiol 2:94PubMedCentralPubMedGoogle Scholar
  93. Grice EA, Segre JA (2012) The human microbiome: our second genome. Annu Rev Genomics Hum Genet 13:151–170PubMedCentralPubMedGoogle Scholar
  94. Groeger D et al (2013) Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes 4(4):325–339PubMedGoogle Scholar
  95. Gulati AS et al (2012) Mouse background strain profoundly influences Paneth cell function and intestinal microbial composition. PLoS One 7(2):e32403PubMedCentralPubMedGoogle Scholar
  96. Hakem A et al (2011) Role of Pirh2 in mediating the regulation of p53 and c-Myc. PLoS Genet 7(11):e1002360PubMedCentralPubMedGoogle Scholar
  97. 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):25–39PubMedGoogle Scholar
  98. Hedges DW, Woon FL (2011) Early-life stress and cognitive outcome. Psychopharmacology (Berl) 214(1):121–130Google Scholar
  99. Hillila MT, Farkkila NJ, Farkkila MA (2010) Societal costs for irritable bowel syndrome—a population based study. Scand J Gastroenterol 45(5):582–591PubMedGoogle Scholar
  100. Holzer P, Reichmann F, Farzi A (2012) Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis. Neuropeptides 46(6):261–274PubMedCentralPubMedGoogle Scholar
  101. Hori T et al (1995) The autonomic nervous system as a communication channel between the brain and the immune system. Neuroimmunomodulation 2(4):203–215PubMedGoogle Scholar
  102. Hornig M (2013) The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol 25(4):488–495PubMedGoogle Scholar
  103. Jeffery IB et al (2012) An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 61(7):997–1006PubMedGoogle Scholar
  104. Jimenez E et al (2008) Is meconium from healthy newborns actually sterile? Res Microbiol 159(3):187–193PubMedGoogle Scholar
  105. Johnson CL, Versalovic J (2012) The human microbiome and its potential importance to pediatrics. Pediatrics 129(5):950–960PubMedGoogle Scholar
  106. 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):3179–3186PubMedGoogle Scholar
  107. Kandel E (2012) The biological mind and art. A conversation with Eric Kandel, MD. Interview by Sue Pondrom. Ann Neurol 72(5):A7–A8PubMedGoogle Scholar
  108. 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–S1178PubMedGoogle Scholar
  109. 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):1243–1251PubMedGoogle Scholar
  110. Kennedy PJ et al (2012) Gut memories: towards a cognitive neurobiology of irritable bowel syndrome. Neurosci Biobehav Rev 36(1):310–340PubMedGoogle Scholar
  111. Kinross J, Nicholson JK (2012) Gut microbiota: Dietary and social modulation of gut microbiota in the elderly. Nat Rev Gastroenterol Hepatol 9(10):563–564PubMedGoogle Scholar
  112. Konieczna P et al (2012) Portrait of an immunoregulatory Bifidobacterium. Gut Microbes 3(3):261–266PubMedGoogle Scholar
  113. 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 9:95PubMedCentralPubMedGoogle Scholar
  114. 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):2261–2270PubMedGoogle Scholar
  115. Larsen N et al (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5(2):e9085PubMedCentralPubMedGoogle Scholar
  116. Ledford JR, Gast DL (2006) Feeding problems in children with autism spectrum disorders : a review. Focus Autism Other Dev Disabl 21:153Google Scholar
  117. Leonard BE (2005) The HPA and immune axes in stress: the involvement of the serotonergic system. Eur Psychiatry 20(Suppl 3):S302–S306PubMedGoogle Scholar
  118. Ley RE et al (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102(31):11070–11075PubMedGoogle Scholar
  119. Ley RE et al (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023PubMedGoogle Scholar
  120. Longstreth GF et al (2006) Functional bowel disorders. Gastroenterology 130(5):1480–1491PubMedGoogle Scholar
  121. Louis P (2012) Does the human gut microbiota contribute to the etiology of autism spectrum disorders? Dig Dis Sci 57(8):1987–1989PubMedGoogle Scholar
  122. Lozupone CA et al (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489(7415):220–230PubMedCentralPubMedGoogle Scholar
  123. Lupien SJ et al (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10(6):434–445PubMedGoogle Scholar
  124. 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):63–68PubMedGoogle Scholar
  125. 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):47–54PubMedGoogle Scholar
  126. Macpherson AJ, Uhr T (2002) Gut flora—mechanisms of regulation. Eur J Surg Suppl 587:53–57PubMedGoogle Scholar
  127. 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):117–124PubMedGoogle Scholar
  128. Marco ML et al (2009) Lifestyle of Lactobacillus plantarum in the mouse caecum. Environ Microbiol 11(10):2747–2757PubMedCentralPubMedGoogle Scholar
  129. Marques TM et al (2010) Programming infant gut microbiota: influence of dietary and environmental factors. Curr Opin Biotechnol 21(2):149–156PubMedGoogle Scholar
  130. Matsumoto M et al (2013) Cerebral low-molecular metabolites influenced by intestinal microbiota: a pilot study. Front Syst Neurosci 7:9PubMedCentralPubMedGoogle Scholar
  131. Matthews DM, Jenks SM (2013) Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice. Behav Processes 96:27–35PubMedGoogle Scholar
  132. Mayer EA (2011) Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 12(8):453–466PubMedGoogle Scholar
  133. Maynard CL et al (2012) Reciprocal interactions of the intestinal microbiota and immune system. Nature 489(7415):231–241PubMedGoogle Scholar
  134. McEwen BS (2012) Brain on stress: how the social environment gets under the skin. Proc Natl Acad Sci USA 109(Suppl 2):17180–17185PubMedGoogle Scholar
  135. McKernan DP et al (2010) The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat. Neurogastroenterol Motil 22 (9), 1029–1035, e268Google Scholar
  136. McLean PG, Borman RA, Lee K (2007) 5-HT in the enteric nervous system: gut function and neuropharmacology. Trends Neurosci 30(1):9–13PubMedGoogle Scholar
  137. 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–e183Google Scholar
  138. Mertz H (2002) Role of the brain and sensory pathways in gastrointestinal sensory disorders in humans. Gut 51(Suppl 1):i29–i33PubMedGoogle Scholar
  139. Mertz H et al (2000) Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology 118(5):842–848PubMedGoogle Scholar
  140. 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):256–261Google Scholar
  141. Moayyedi P et al (2010) The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 59(3):325–332PubMedGoogle Scholar
  142. Mocking RJ et al (2013) Relationship between the hypothalamic–pituitary–adrenal-axis and fatty acid metabolism in recurrent depression. Psychoneuroendocrinology 38(9):1607–1617PubMedGoogle Scholar
  143. Moore P et al (2000) Clinical and physiological consequences of rapid tryptophan depletion. Neuropsychopharmacology 23(6):601–622PubMedGoogle Scholar
  144. Mulle JG, Sharp WG, Cubells JF (2013) The gut microbiome: a new frontier in autism research. Curr Psychiatry Rep 15(2):337PubMedCentralPubMedGoogle Scholar
  145. Murphy EF et al (2013) Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut 62(2):220–226PubMedGoogle Scholar
  146. Myint AM et al (2007) Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord 98(1–2):143–151PubMedGoogle Scholar
  147. Myint AM et al (2013) Tryptophan metabolism and immunogenetics in major depression: a role for interferon-gamma gene. Brain Behav Immun 31:128–133PubMedGoogle Scholar
  148. Nance DM, Sanders VM (2007) Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 21(6):736–745PubMedCentralPubMedGoogle Scholar
  149. Naslund J et al (2013) Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat. Psychopharmacology (Berl) 230(1):29–35Google Scholar
  150. Neufeld KM et al (2011) Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 23(3): 255–264, e119Google Scholar
  151. Nicholson JK et al (2012) Host-gut microbiota metabolic interactions. Science 336(6086):1262–1267PubMedGoogle Scholar
  152. 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):521–528Google Scholar
  153. Nolen-Hoeksema S, Larson J, Grayson C (1999) Explaining the gender difference in depressive symptoms. J Pers Soc Psychol 77(5):1061–1072PubMedGoogle Scholar
  154. Nutt DJ, Malizia AL (2004) Structural and functional brain changes in posttraumatic stress disorder. J Clin Psychiatry 65(Suppl 1):11–17PubMedGoogle Scholar
  155. 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):1738–1747Google Scholar
  156. Olivares M, Laparra JM, Sanz Y (2013) Host genotype, intestinal microbiota and inflammatory disorders. Br J Nutr 109(Suppl 2):S76–S80PubMedGoogle Scholar
  157. 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):263–267PubMedGoogle Scholar
  158. O’Mahony SM et al (2011) Maternal separation as a model of brain–gut axis dysfunction. Psychopharmacology (Berl) 214(1):71–88Google Scholar
  159. Ozawa E (1955) Studies on growth promotion by antibiotics. II. Results of aurofac administration to infants. J Antibiot (Tokyo) 8(6):212–214Google Scholar
  160. Parfrey LW, Knight R (2012) Spatial and temporal variability of the human microbiota. Clin Microbiol Infect 18(Suppl 4):8–11PubMedGoogle Scholar
  161. Parkes GC, Sanderson JD, Whelan K (2010) Treating irritable bowel syndrome with probiotics: the evidence. Proc Nutr Soc 69(2):187–194PubMedGoogle Scholar
  162. 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–G220PubMedGoogle Scholar
  163. Pickett BE et al (2012) ViPR: an open bioinformatics database and analysis resource for virology research. Nucleic Acids Res 40(Database issue):D593–D598PubMedCentralPubMedGoogle Scholar
  164. Pimentel M, Lezcano S (2007) Irritable bowel syndrome: bacterial overgrowth—what’s known and what to do. Curr Treat Options Gastroenterol 10(4):328–337PubMedGoogle Scholar
  165. Qin J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(7285):59–65PubMedCentralPubMedGoogle Scholar
  166. Qin J et al (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490(7418):55–60PubMedGoogle Scholar
  167. 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):4948–4959PubMedGoogle Scholar
  168. Rajilic-Stojanovic M, Smidt H, de Vos WM (2007) Diversity of the human gastrointestinal tract microbiota revisited. Environ Microbiol 9(9):2125–2136PubMedGoogle Scholar
  169. Relman DA (2012) The human microbiome: ecosystem resilience and health. Nutr Rev 70(Suppl 1):S2–S9PubMedCentralPubMedGoogle Scholar
  170. Rhee SH, Pothoulakis C, Mayer EA (2009) Principles and clinical implications of the brain–gut–enteric microbiota axis. Nat Rev Gastroenterol Hepatol 6(5):306–314PubMedGoogle Scholar
  171. 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):243–246PubMedGoogle Scholar
  172. Rousseaux C et al (2007) Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med 13(1):35–37PubMedGoogle Scholar
  173. Ruddick JP et al (2006) Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med 8(20):1–27PubMedGoogle Scholar
  174. Salonen A, de Vos WM, Palva A (2010) Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives. Microbiology 156(Pt 11):3205–3215PubMedGoogle Scholar
  175. Sam AH et al (2012) The role of the gut/brain axis in modulating food intake. Neuropharmacology 63(1):46–56Google Scholar
  176. Sandler RH et al (2000) Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol 15(7):429–435PubMedGoogle Scholar
  177. Saulnier DM et al (2013) The intestinal microbiome, probiotics and prebiotics in neurogastroenterology. Gut Microbes 4(1):17–27PubMedGoogle Scholar
  178. 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):756–764Google Scholar
  179. Schellekens H et al (2012) Ghrelin signalling and obesity: at the interface of stress, mood and food reward. Pharmacol Ther 135(3):316–326Google Scholar
  180. Schultz ST et al (2006) Breastfeeding, infant formula supplementation, and autistic disorder: the results of a parent survey. Int Breastfeed J 1:16PubMedCentralPubMedGoogle Scholar
  181. 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, BaselGoogle Scholar
  182. Selye H (1936) A syndrome produced by diverse nocuous agents. 1936. J Neuropsychiatry Clin Neurosci 10(2):230–231Google Scholar
  183. 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):2159–2173Google Scholar
  184. 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):25–35PubMedGoogle Scholar
  185. 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):e413PubMedCentralPubMedGoogle Scholar
  186. Spiller R, Garsed K (2009) Postinfectious irritable bowel syndrome. Gastroenterology 136(6):1979–1988PubMedGoogle Scholar
  187. Squire LR, Wixted JT (2011) The cognitive neuroscience of human memory since H.M. Annu Rev Neurosci 34:259–288PubMedCentralPubMedGoogle Scholar
  188. 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):1–210PubMedGoogle Scholar
  189. Sudo N et al (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 558(Pt 1):263–275PubMedGoogle Scholar
  190. 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):331–338PubMedGoogle Scholar
  191. Tack J et al (2006) A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut 55(8):1095–1103PubMedGoogle Scholar
  192. 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, e114–5Google Scholar
  193. Tang WY, Ho SM (2007) Epigenetic reprogramming and imprinting in origins of disease. Rev Endocr Metab Disord 8(2):173–182PubMedGoogle Scholar
  194. Tannock GW, Savage DC (1974) Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect Immun 9(3):591–598PubMedCentralPubMedGoogle Scholar
  195. Taylor MW, Feng GS (1991) Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J 5(11):2516–2522PubMedGoogle Scholar
  196. Tillisch K et al (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144(7):1394–1401, 1401.e1–1401.e4Google Scholar
  197. Timoveyev L et al (2002) Stability to sound stress and changeability in intestinal microflora. Eur Psychiatry 17(Suppl 1):200Google Scholar
  198. 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):481–489PubMedGoogle Scholar
  199. Tremaroli V, Bäckhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489(7415):242–249PubMedGoogle Scholar
  200. Turnbaugh PJ, Gordon JI (2009) The core gut microbiome, energy balance and obesity. J Physiol 587(Pt 17):4153–4158PubMedGoogle Scholar
  201. Turnbaugh PJ et al (2009) A core gut microbiome in obese and lean twins. Nature 457(7228):480–484PubMedCentralPubMedGoogle Scholar
  202. Ursell LK et al (2012) The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites. J Allergy Clin Immunol 129(5):1204–1208PubMedCentralPubMedGoogle Scholar
  203. Vaishampayan PA et al (2010) Comparative metagenomics and population dynamics of the gut microbiota in mother and infant. Genome Biol Evol 2:53–66PubMedCentralPubMedGoogle Scholar
  204. Valles Y et al (2012) Metagenomics and development of the gut microbiota in infants. Clin Microbiol Infect 18(Suppl 4):21–26PubMedGoogle Scholar
  205. Van Loo JA (2004) Prebiotics promote good health: the basis, the potential, and the emerging evidence. J Clin Gastroenterol 38(6 Suppl):S70–S75PubMedGoogle Scholar
  206. van Nood E et al (2013) Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 368(5):407–415PubMedGoogle Scholar
  207. Verdu EF et al (2006) Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut 55(2):182–190PubMedGoogle Scholar
  208. Vighi G et al (2008) Allergy and the gastrointestinal system. Clin Exp Immunol 153(Suppl 1):3–6PubMedCentralPubMedGoogle Scholar
  209. Wall R et al (2010) Impact of administered bifidobacterium on murine host fatty acid composition. Lipids 45(5):429–436PubMedGoogle Scholar
  210. 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):1278–1287PubMedGoogle Scholar
  211. 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):2096–2102PubMedGoogle Scholar
  212. Weberpals JI, Koti M, Squire JA (2011) Targeting genetic and epigenetic alterations in the treatment of serous ovarian cancer. Cancer Genet 204(10):525–535PubMedGoogle Scholar
  213. Weilburg JB (2004) An overview of SSRI and SNRI therapies for depression. Manag Care 13(6 Suppl Depression):25–33PubMedGoogle Scholar
  214. 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):e24585PubMedCentralPubMedGoogle Scholar
  215. 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):18–21PubMedGoogle Scholar
  216. Wrase J et al (2006) Serotonergic dysfunction: brain imaging and behavioral correlates. Cogn Affect Behav Neurosci 6(1):53–61PubMedGoogle Scholar
  217. Zucchelli M et al (2011) Association of TNFSF15 polymorphism with irritable bowel syndrome. Gut 60(12):1671–1677PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rachel D. Moloney
    • 1
    • 2
  • Lieve Desbonnet
    • 1
    • 3
  • Gerard Clarke
    • 1
    • 2
  • Timothy G. Dinan
    • 1
    • 2
  • John F. Cryan
    • 1
    • 3
  1. 1.Laboratory of NeuroGastroenterology, Alimentary Pharmabiotic CentreUniversity College CorkCorkIreland
  2. 2.Department of PsychiatryUniversity College CorkCorkIreland
  3. 3.Department of Anatomy and NeuroscienceUniversity College CorkCorkIreland

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