Relationship between the gut microbiome and brain function

Nutrition Reviews

Volumn 76, Issue 7, 2018, Pages 481-496

  Hasan Mohajeri, M ^a   La Fata, Giorgio ^a   Steinert, Robert E ^a   Weber, Peter ^a  

^a DSM NUTRITIONAL PRODUCTS LTD   (Switzerland)

Author keywords

Alzheimer; Anxiety; Cognition; Depression; Memory; Microbiome; Prevention; Probiotics; Stress

Indexed keywords

ANXIETY; ARTICLE; BEHAVIOR; BRAIN FUNCTION; COGNITION; DEPRESSION; HUMAN; INTESTINE FLORA; INTESTINE INNERVATION; MAMMAL; NERVE CELL; NERVE CELL EXCITABILITY; NEUROMODULATION; NONHUMAN; STRESS; ADULT; BRAIN; FEMALE; GASTROINTESTINAL TRACT; MALE; MENTAL STRESS; MICROBIOLOGY; NERVOUS SYSTEM FUNCTION; PHYSIOLOGY;

PROBIOTIC AGENT;

ADULT; ANXIETY; BRAIN; DEPRESSION; FEMALE; GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL TRACT; HUMANS; MALE; NERVOUS SYSTEM PHYSIOLOGICAL PHENOMENA; PROBIOTICS; STRESS, PSYCHOLOGICAL;

EID: 85047296199     PISSN: 00296643     EISSN: 17534887     Source Type: Journal    
DOI: 10.1093/nutrit/nuy009     Document Type: Article

References (165)

1. Kennedy RJ, Kirk SJ, Gardiner KR. Probiotics [comment on Br J Surg 2001;88:161-162]. Br J Surg. 2001;88:1018-1019
2. Gruner D, Paris S, Schwendicke F. Probiotics for managing caries and periodontitis: systematic review and meta-analysis. J Dent. 2016;48:16-25
3. Jafarnejad S, Shab-Bidar S, Speakman JR, et al. Probiotics reduce the risk of antibiotic-associated diarrhea in adults (18-64 years) but not the elderly (>65 years): a meta-analysis. Nutr Clin Pract. 2016;31:502-513
4. Martin-Cabezas R, Davideau JL, Tenenbaum H, et al. Clinical efficacy of probiotics as an adjunctive therapy to non-surgical periodontal treatment of chronic periodontitis: a systematic review and meta-analysis. J Clin Periodontol. 2016;43:520-530
5. Zhang Q, Wu Y, Fei X. Effect of probiotics on body weight and body-mass index: a systematic review and meta-analysis of randomized, controlled trials. Int J Food Sci Nutr. 2015;67:571-580
6. Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444: 1027-1031
7. Backhed F, Ley RE, Sonnenburg JL, P, et al. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915-1920
8. Jumpstart Consortium Human Microbiome Project Data Generation Working Group. Evaluation of 16S rDNA-based community profiling for human microbiome research. PLoS One. 2012;7:e39315. doi:10.1371/journal.pone. 0039315
9. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222-227
10. Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature. 2007;449:804-810
11. Gill SR, Pop M, Deboy RT, et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355-1359
12. Saito YA, Schoenfeld P, Locke GR, 3rd. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002;97:1910-1915
13. Backhed F, Fraser CM, Ringel Y, et al. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe. 2012;12:611-622
14. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559-563
15. Mayer EA, Knight R, Mazmanian SK, et al. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014;34:15490-15496
16. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13:701-712
17. Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220-230
18. Penders J, Thijs C, Vink C, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006;118:511-521
19. Kennedy PJ, Cryan JF, Dinan TG, et al. Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology. 2017;112(pt B):399-412
20. Rodriguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050. doi:10.3402/mehd.v26.26050
21. Borre YE, O'Keeffe GW, Clarke G, et al. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014;20:509-518
22. Palmer C, Bik EM, DiGiulio DB, et al. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5:e177. doi:10.1371/journal.pbio.0050177
23. Claesson MJ, Cusack S, O'Sullivan O, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA. 2011;108(suppl 1):4586-4591
24. Knights D, Ward TL, McKinlay CE, et al. Rethinking "enterotypes." Cell Host Microbe. 2014;16:433-437
25. McVey Neufeld KA, Luczynski P, Seira Oriach C, et al. What's bugging your teen?-The microbiota and adolescent mental health. Neurosci Biobehav Rev. 2016;70:300-312
26. Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36:305-312
27. Bercik P, Denou E, Collins J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141:599-609. 609 e591-593
28. Cryan JF, O'Mahony SM. The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil. 2011;23:187-192
29. Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol. 2009;6:306-314
30. El Aidy S, Dinan TG, Cryan JF. Gut microbiota: the conductor in the orchestra of immune-neuroendocrine communication. Clin Ther. 2015;37:954-967
31. Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125:926-938
32. Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol. 2012;9:286-294
33. Badawy AA. Tryptophan availability for kynurenine pathway metabolism across the life span: control mechanisms and focus on aging, exercise, diet and nutritional supplements. Neuropharmacology. 2017;112(pt B):248-263
34. Desbonnet L, Clarke G, Traplin A, et al. Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav Immun. 2015;48:165-173
35. Erny D, Hrabe de Angelis AL, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18:965-977
36. Hoban AE, Stilling RM, Ryan FJ, et al. Regulation of prefrontal cortex myelination by the microbiota. Transl Psychiatry. 2016;6:e774
37. Ogbonnaya ES, Clarke G, Shanahan F, et al. Adult hippocampal neurogenesis is regulated by the microbiome. Biol Psychiatry. 2015;78:e7-e9
38. Collins SM, Kassam Z, Bercik P. The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Curr Opin Microbiol. 2013;16:240-245
39. Mayer EA, Aziz Q, Coen S, et al. Brain imaging approaches to the study of functional GI disorders: a Rome Working Team report. Neurogastroenterol Motil. 2009;21:579-596
40. Mayer EA, Tillisch K, Bradesi S. Review article: modulation of the brain-gut axis as a therapeutic approach in gastrointestinal disease. Aliment Pharmacol Ther. 2006;24:919-933
41. Halvorson HA, Schlett CD, Riddle MS. Postinfectious irritable bowel syndrome-a meta-analysis. Am J Gastroenterol. 2006;101:1894-1899
42. Schwille-Kiuntke J, Enck P, Zendler C, et al. Postinfectious irritable bowel syndrome: follow-up of a patient cohort of confirmed cases of bacterial infection with Salmonella or Campylobacter. Neurogastroenterol Motil. 2011;23:e479-e488
43. Maxwell PR, Rink E, Kumar D, et al. Antibiotics increase functional abdominal symptoms. Am J Gastroenterol. 2002;97:104-108
44. Mayer EA. The neurobiology of stress and gastrointestinal disease. Gut. 2000;47:861-869
45. Mayer EA. Psychological stress and colitis. Gut. 2000;46:595-596
46. Sharkey KA, Savidge TC. Role of enteric neurotransmission in host defense and protection of the gastrointestinal tract. Auton Neurosci. 2014;181:94-106
47. Costa M, Brookes SJ, Hennig GW. Anatomy and physiology of the enteric nervous system. Gut. 2000;47(suppl 4):iv15-iv19; discussion iv26
48. Costa M, Glise H, Sjodahl R. The enteric nervous system in health and disease. Gut. 2000;47(suppl 4):iv1. doi:10.1136/gut.47.suppl_4.iv1
49. Furness JB. The organisation of the autonomic nervous system: peripheral connections. Auton Neurosci. 2006;130:1-5
50. Bercik P, Verdu EF, Foster JA, et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology. 2010;139:2102.e1-2112.e1
51. Bravo JA, Forsythe P, Chew MV, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA. 2011;108:16050-16055
52. Lyte M, Li W, Opitz N, et al. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium. Physiol Behav. 2006;89:350-357
53. Gilbert K, Arseneault-Breard J, Flores Monaco F, et al. Attenuation of postmyocardial infarction depression in rats by n-3 fatty acids or probiotics starting after the onset of reperfusion. Br J Nutr. 2013;109:50-56
54. Oike H, Aoki-Yoshida A, Kimoto-Nira H, et al. Dietary intake of heat-killed Lactococcus lactis H61 delays age-related hearing loss in C57BL/6J mice. Sci Rep. 2016;6:23556. doi:10.1038/srep23556
55. Perez-Burgos A, Wang B, Mao YK, et al. Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. Am J Physiol Gastrointest Liver Physiol. 2013;304:G211-G220
56. Galligan JJ, Furness JB, Costa M. Migration of the myoelectric complex after interruption of the myenteric plexus: intestinal transection and regeneration of enteric nerves in the guinea pig. Gastroenterology. 1989;97:1135-1146
57. McVey Neufeld KA, Mao YK, Bienenstock J, et al. The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol Motil. 2013;25:183-e88
58. Wu RY, Pasyk M, Wang B, et al. Spatiotemporal maps reveal regional differences in the effects on gut motility for Lactobacillus reuteri and rhamnosus strains. Neurogastroenterol Motil. 2013;25:e205-e214
59. McVey Neufeld KA, Perez-Burgos A, Mao YK, et al. The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin. Neurogastroenterol Motil. 2015;27:627-636
60. Perez-Burgos A, Wang L, McVey Neufeld KA, et al. The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938. J Physiol (Lond). 2015;593:3943-3957
61. Lee YS, Taylor AN, Reimers TJ, et al. Calbindin-D in peripheral nerve cells is vitamin D and calcium dependent. Proc Natl Acad Sci USA. 1987;84:7344-7348
62. Meyer J, Fullmer CS, Wasserman RH, et al. Dietary restriction of calcium, phosphorus, and vitamin D elicits differential regulation of the mRNAs for avian intestinal calbindin-D28k and the 1, 25-dihydroxyvitamin D3 receptor. J Bone Miner Res. 1992;7:441-448
63. Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000;23:477-501
64. Heim C, NemeroffCB. Neurobiology of posttraumatic stress disorder. CNS Spectr. 2009;14(1 suppl 1):13-24
65. Walker EF, Trotman HD, Pearce BD, et al. Cortisol levels and risk for psychosis: initial findings from the North American Prodrome Longitudinal Study. Biol Psychiatry. 2013;74:410-417
66. Spencer RL, Deak T. A users guide to HPA axis research. Physiol Behav. 2017;178:43-65
67. Luczynski P, McVey Neufeld KA, et al. Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior. Int J Neuropsychopharmacol. 2016;19. doi:10.1093/ijnp/pyw020
68. Smith CJ, Emge JR, Berzins K, et al. Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice. Am J Physiol Gastrointest Liver Physiol. 2014;307:G793-G802
69. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558:263-275
70. Desbonnet L, Garrett L, Clarke G, et al. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170:1179-1188
71. Stilling RM, Ryan FJ, Hoban AE, et al. Microbes & neurodevelopment-absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala. Brain Behav Immun. 2015;50:209-220
72. D'Mello C, Ronaghan N, Zaheer R, et al. Probiotics improve inflammationassociated sickness behavior by altering communication between the peripheral immune system and the brain. J Neurosci. 2015;35:10821-10830
73. Messaoudi M, Lalonde R, Violle N, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105:755-764
74. Desbonnet L, Garrett L, Clarke G, et al. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43:164-174
75. Gareau MG, Jury J, MacQueen G, et al. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut. 2007;56:1522-1528
76. Frohlich EE, Farzi A, Mayerhofer R, et al. Cognitive impairment by antibioticinduced gut dysbiosis: analysis of gut microbiota-brain communication. Brain Behav Immun. 2016;56:140-155
77. Li W, Dowd SE, Scurlock B, et al. Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria. Physiol Behav. 2009;96:557-567
78. Ohland CL, Kish L, Bell H, et al. Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology. 2013;38:1738-1747
79. Davari S, Talaei SA, Alaei H, et al. Probiotics treatment improves diabetesinduced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience. 2013;240:287-296
80. Gareau MG, Wine E, Rodrigues DM, et al. Bacterial infection causes stressinduced memory dysfunction in mice. Gut. 2011;60:307-317
81. Lyte M, Varcoe JJ, Bailey MT. Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation. Physiol Behav. 1998;65:63-68
82. Gacias M, Gaspari S, Santos PM, et al. Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior. eLife. 2016;5. doi:10.7554/eLife.13442
83. Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressivelike behaviors through a pathway mediated by the host's metabolism. Mol Psychiatry. 2016;21:786-796
84. Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 2016;167:1469.e12-1480.e12
85. Diaz Heijtz R, Wang S, Anuar F, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA. 2011;108:3047-3052
86. Neufeld KM, Kang N, Bienenstock J, et al. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011;23:255-e119
87. Clarke G, Grenham S, Scully P, et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry. 2013;18:666-673
88. Desbonnet L, Clarke G, Shanahan F, et al. Microbiota is essential for social development in the mouse. Mol Psychiatry. 2014;19:146-148
89. Arentsen T, Raith H, Qian Y, et al. Host microbiota modulates development of social preference in mice. Microb Ecol Health Dis. 2015;26:29719. doi:10.3402/mehd.v26.29719
90. Dhiman RK, Rana B, Agrawal S, et al. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology. 2014;147:1327.e3-1337.e3
91. World Health Organization. Depression: let's talk. WHO website. http://www. who.int/mental_health/management/depression/en/. Accessed March 21, 2018
92. Midtvedt T. Society for microbial ecology, microbial ecology in health and disease, and the future. Microb Ecol Health Dis. 2013;24. doi:10.3402/mehd.v24i0. 23315
93. Savignac HM, Corona G, Mills H, et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochem Int. 2013;63:756-764
94. Savignac HM, Kiely B, Dinan TG, et al. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil. 2014;26:1615-1627
95. Wong ML, Inserra A, Lewis MD, et al. Inflammasome signaling affects anxietyand depressive-like behavior and gut microbiome composition. Mol Psychiatry. 2016;21:797-805
96. Mohammadi AA, Jazayeri S, Khosravi-Darani K, et al. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: a randomized, doubleblind, placebo-controlled trial in petrochemical workers. Nutr Neurosci. 2016;19:387-395
97. Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007;61:355-361
98. Allen AP, Hutch W, Borre YE, et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl Psychiatry. 2016;6:e939. doi:10.1038/tp.2016.191
99. Tillisch K, Labus J, Kilpatrick L, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013;144:1394.e4-1401.e4
100. Chung Y-C, Jin H-M, Cui Y, et al. Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults. J Funct Foods. 2014;10:465-474
101. Brenner DM, Moeller MJ, Chey WD, et al. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol. 2009;104:1033-1049
102. Akbari E, Asemi Z, Daneshvar Kakhaki R, et al. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trial. Front Aging Neurosci. 2016;8:256. doi:10.3389/fnagi.2016.00256
103. Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, et al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial. Nutrition. 2016;32:315-320
104. Schmidt K, Cowen PJ, Harmer CJ, et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl). 2015;232:1793-1801
105. Steenbergen L, Sellaro R, van Hemert S, et al. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015;48:258-264
106. Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186-194
107. Naseribafrouei A, Hestad K, Avershina E, et al. Correlation between the human fecal microbiota and depression. Neurogastroenterol Motil. 2014;26:1155-1162
108. Jagmag SA, Tripathi N, Jha MP, et al. Exploring the relationship between gut microbiome and depression. Trends Gastroenterol. 2016;1:1-5
109. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013;74:720-726
110. Ait-Belgnaoui A, Durand H, Cartier C, et al. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology. 2012;37:1885-1895
111. Evrensel A, Ceylan ME. The gut-brain axis: the missing link in depression. Clin Psychopharmacol Neurosci. 2015;13:239-244
112. Golubeva AV, Crampton S, Desbonnet L, et al. Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood. Psychoneuroendocrinology. 2015;60:58-74
113. Jasarevic E, Howerton CL, Howard CD, et al. Alterations in the vaginal microbiome by maternal stress are associated with metabolic reprogramming of the offspring gut and brain. Endocrinology. 2015;156:3265-3276
114. Bailey MT, Coe CL. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev Psychobiol. 1999;35:146-155
115. O'Mahony SM, Marchesi JR, Scully P, et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009;65:263-267
116. Bailey MT, Dowd SE, Galley JD, et al. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun. 2011;25:397-407
117. Bharwani A, Mian MF, Foster JA, et al. Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology. 2016;63:217-227
118. Galley JD, Nelson MC, Yu Z, et al. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota. BMC Microbiol. 2014;14:189. doi:10.1186/1471-2180-14-189
119. Reber SO, Siebler PH, Donner NC, et al. Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. Proc Natl Acad Sci USA. 2016;113:E3130-E3139
120. Prenderville JA, Kennedy PJ, Dinan TG, et al. Adding fuel to the fire: the impact of stress on the ageing brain. Trends Neurosci. 2015;38:13-25
121. Gareau MG. Microbiota-gut-brain axis and cognitive function. Adv Exp Med Biol. 2014;817:357-371
122. Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe. 2015;17:565-576
123. Levenson JM, O'Riordan KJ, Brown KD, et al. Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem. 2004;279:40545-40559
124. Lattal KM, Barrett RM, Wood MA. Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci. 2007;121:1125-1131
125. Fischer A, Sananbenesi F, Wang X, et al. Recovery of learning and memory is associated with chromatin remodelling. Nature. 2007;447:178-182
126. Govindarajan N, Agis-Balboa RC, Walter J, et al. Sodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression. J Alzheimers Dis. 2011;26:187-197
127. Sharma S, Taliyan R, Singh S. Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: modulation of histone deacetylase activity. Behav Brain Res. 2015;291:306-314
128. Ryu H, Smith K, Camelo SI, et al. Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. J Neurochem. 2005;93:1087-1098
129. Ferrante RJ, Kubilus JK, Lee J, et al. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice. J Neurosci. 2003;23:9418-9427
130. Chou AH, Chen SY, Yeh TH, et al. HDAC inhibitor sodium butyrate reverses transcriptional downregulation and ameliorates ataxic symptoms in a transgenic mouse model of SCA3. Neurobiol Dis. 2011;41:481-488
131. Bravo JA, Julio-Pieper M, Forsythe P, et al. Communication between gastrointestinal bacteria and the nervous system. Curr Opin Pharmacol. 2012;12:667-672
132. Morgan MA, Romanski LM, LeDoux JE. Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett. 1993;163:109-113
133. Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions. Science. 2012;336:1262-1267
134. Stilling RM, van de Wouw M, Clarke G, et al. The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016;99:110-132
135. Farrugia G, Szurszewski JH. Carbon monoxide, hydrogen sulfide, and nitric oxide as signaling molecules in the gastrointestinal tract. Gastroenterology. 2014;147:303-313
136. Savidge TC. S-nitrosothiol signals in the enteric nervous system: lessons learnt from big brother. Front Neurosci. 2011;5:31. doi:10.3389/fnins.2011.00031
137. Gulbransen BD, Bashashati M, Hirota SA, et al. Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat Med. 2012;18:600-604
138. Gulbransen BD, Sharkey KA. Novel functional roles for enteric glia in the gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 2012;9:625-632
139. Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014;38:1-12
140. Kabouridis PS, Lasrado R, McCallum S, et al. Microbiota controls the homeostasis of glial cells in the gut lamina propria. Neuron. 2015;85:289-295
141. MacEachern SJ, Patel BA, Keenan CM, et al. Inhibiting inducible nitric oxide synthase in enteric glia restores electrogenic ion transport in mice with colitis. Gastroenterology. 2015;149:445.e3-455.e3
142. MacEachern SJ, Patel BA, McKay DM, et al. Nitric oxide regulation of colonic epithelial ion transport: a novel role for enteric glia in the myenteric plexus. J Physiol. 2011;589:3333-3348
143. Savidge TC, Newman P, Pothoulakis C, et al. Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology. 2007;132:1344-1358
144. Grubiśić V, Gulbransen BD. Enteric glia: the most alimentary of all glia. J Physiol. 2017;595:557-570
145. Alemi F, Poole DP, Chiu J, et al. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology. 2013;144:145-154
146. Sorg JA, Sonenshein AL. Chenodeoxycholate is an inhibitor of Clostridium difficile spore germination. J Bacteriol. 2009;191:1115-1117
147. Sorg JA, Sonenshein AL. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J Bacteriol. 2010;192:4983-4990
148. Chen C, Brown DR, Xie Y, et al. Catecholamines modulate Escherichia coli O157:H7 adherence to murine cecal mucosa. Shock. 2003;20:183-188
149. Chen C, Lyte M, Stevens MP, et al. Mucosally-directed adrenergic nerves and sympathomimetic drugs enhance non-intimate adherence of Escherichia coli O157:H7 to porcine cecum and colon. Eur J Pharmacol. 2006;539:116-124
150. Freestone PP, Sandrini SM, Haigh RD, et al. Microbial endocrinology: how stress influences susceptibility to infection. Trends Microbiol. 2008;16:55-64
151. Hughes DT, Clarke MB, Yamamoto K, et al. The QseC adrenergic signaling cascade in enterohemorrhagic E. coli (EHEC). PLoS Pathog. 2009;5:e1000553. doi:10.1371/journal.ppat.1000553
152. Lyte M, Vulchanova L, Brown DR. Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res. 2011;343:23-32
153. Savidge TC. Epigenetic regulation of enteric neurotransmission by gut bacteria. Front Cell Neurosci. 2015;9:503. doi:10.3389/fncel.2015.00503
154. Ruddick JP, Evans AK, Nutt DJ, et al. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med. 2006;8:1-27
155. Ohland CL, Pankiv E, Baker G, et al. Western diet-induced anxiolytic effects in mice are associated with alterations in tryptophan metabolism. Nutr Neurosci. 2016;19:337-345
156. Reigstad CS, Salmonson CE, Rainey JF III, et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 2015;29:1395-1403
157. Özoğul F. Production of biogenic amines by Morganella morganii, Klebsiella pneumoniae and Hafnia alvei using a rapid HPLC method. Eur Food Res Technol. 2004;219:465-469. 219(5): 465-469
158. Shishov VA, Kirovskaia TA, Kudrin VS, et al. Amine neuromediators, their precursors, and oxidation products in the culture of Escherichia coli K-12 [in Russian]. Appl Biochem Microbiol. 2009;45:550-554
159. Barrett E, Ross RP, O'Toole PW, et al. c-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol. 2012;113:411-417
160. Romano KA, Vivas EI, Amador-Noguez D, et al. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. MBio. 2015;6:e02481. doi:10.1128/mBio.02481-14
161. Kelly JR, Kennedy PJ, Cryan JF, et al. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015;9:392. doi:10.3389/fncel.2015.00392
162. Luczynski P, Whelan SO, O'Sullivan C, et al. Adult microbiota-deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus. Eur J Neurosci. 2016;44:2654-2666
163. Simren M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome Foundation report. Gut. 2013;62:159-176
164. Margolis KG, Gershon MD. Neuropeptides and inflammatory bowel disease. Curr Opin Gastroenterol. 2009;25:503-511
165. Lomax AE, Sharkey KA, Furness JB. The participation of the sympathetic innervation of the gastrointestinal tract in disease states. Neurogastroenterol Motil. 2010;22:7-18