Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals

Trends in Neurosciences

Volumn 39, Issue 11, 2016, Pages 763-781

  Sarkar, Amar ^a   Lehto, Soili M ^b,c   Harty, Siobhán ^a   Dinan, Timothy G ^d   Cryan, John F ^d   Burnet, Philip W J ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF EASTERN FINLAND   (Finland)

^c KUOPIO UNIVERSITY HOSPITAL   (Finland)

^d UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

gut brain axis; interkingdom signalling; microbiome; microbiota; prebiotics; probiotics

Indexed keywords

DRUG METABOLITE; GLUCOCORTICOID; PREBIOTIC AGENT; PROBIOTIC AGENT; PSYCHOBIOTIC AGENT; UNCLASSIFIED DRUG;

BACTERIAL IMMUNITY; COGNITION ASSESSMENT; DRUG EFFECT; DRUG MECHANISM; EMOTION; HUMAN; INTESTINE FLORA; INTESTINE INNERVATION; MENTAL DISEASE; MICROBIOME; NEUROPHARMACOLOGY; NONHUMAN; PRIORITY JOURNAL; PSYCHOPHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; BRAIN; GASTROINTESTINAL TRACT; METABOLISM; MICROBIOLOGY; MICROFLORA; PARASITOLOGY; PHYSIOLOGY;

ANIMALS; BRAIN; EMOTIONS; GASTROINTESTINAL TRACT; HUMANS; MICROBIOTA; PREBIOTICS; PROBIOTICS;

EID: 84994887788     PISSN: 01662236     EISSN: 1878108X     Source Type: Journal    
DOI: 10.1016/j.tins.2016.09.002     Document Type: Review

References (155)

1. 1 Sudo, N., et al. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J. Physiol. 558 (2004), 263–275.
2. 2 Hooper, L.V., et al. Interactions between the microbiota and the immune system. Science 336 (2012), 1268–1273.
3. 3 Kau, A.L., et al. Human nutrition, the gut microbiome and the immune system. Nature 474 (2011), 327–336.
4. 4 Le Chatelier, E., et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500 (2013), 541–546.
5. 5 Turnbaugh, P.J., et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444 (2006), 1027–1031.
6. 6 Bravo, J.A., et al. Communication between gastrointestinal bacteria and the nervous system. Curr. Opin. Pharmacol. 12 (2012), 667–672.
7. 7 Foster, J.A., Neufeld, K.A.M., Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 36 (2013), 305–312.
8. 8 Dinan, T.G., et al. Psychobiotics: a novel class of psychotropic. Biol. Psychiatry 74 (2013), 720–726.
9. 9 Mayer, E.A., et al. Gut microbes and the brain: paradigm shift in neuroscience. J. Neurosci. 34 (2014), 15490–15496.
10. 10 Burnet, P.W., Cowen, P.J., Psychobiotics highlight the pathways to happiness. Biol. Psychiatry 74 (2013), 708–709.
11. 11 Sansonetti, P.J., Medzhitov, R., Learning tolerance while fighting ignorance. Cell 138 (2009), 416–420.
12. 12 Gibson, G.R., et al. Dietary prebiotics: current status and new definition. Food Sci. Technol. Bull. Funct. Foods 7 (2010), 1–19.
13. 13 Dowlati, Y., et al. A meta-analysis of cytokines in major depression. Biol. Psychiatry 67 (2010), 446–457.
14. 14 Udina, M., et al. Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J. Clin. Psychiatry 73 (2012), 1128–1138.
15. 15 McNutt, M.D., et al. Neurobehavioral effects of interferon-α in patients with hepatitis C: symptom dimensions and responsiveness to paroxetine. Neuropsychopharmacology 37 (2012), 1444–1454.
16. 16 Lu, Y., et al. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory?. Neurobiol. Learn. Mem. 89 (2008), 312–323.
17. 17 Heldt, S.A., et al. Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Mol. Psychiatry 12 (2007), 656–670.
18. 18 Martinowich, K., Lu, B., Interaction between BDNF and serotonin: role in mood disorders. Neuropsychopharmacology 33 (2008), 73–83.
19. 19 Desbonnet, L., et al. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 170 (2010), 1179–1188.
20. 20 Gareau, M.G., et al. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut 56 (2007), 1522–1528.
21. 21 Bravo, J.A., 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. U.S.A. 108 (2011), 16050–16055.
22. 22 Matthews, D.M., Jenks, S.M., Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice. Behav. Processes 96 (2013), 27–35.
23. 23 Desbonnet, L., et al. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J. Psychiatr. Res. 43 (2008), 164–174.
24. 24 Liang, S., et al. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress. Neuroscience 310 (2015), 561–577.
25. 25 Janik, R., et al. Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate. NeuroImage 125 (2016), 988–995.
26. 26 Alander, M., et al. Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl. Environ. Microbiol. 65 (1999), 351–354.
27. 27 Savignac, H.M., et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochem. Int. 63 (2013), 756–764.
28. 28 Li, F., Tsien, J.Z., Memory and the NMDA receptors. N. Engl. J. Med. 361 (2009), 302–303.
29. 29 Vázquez, E., et al. Effects of a human milk oligosaccharide, 2′-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents. J. Nutr. Biochem. 26 (2015), 455–465.
30. 30 Williams, S., et al. Neonatal prebiotic (BGOS) supplementation increases the levels of synaptophysin, GluN2A-subunits and BDNF proteins in the adult rat hippocampus. Synapse 70 (2016), 121–124.
31. 31 Oliveros, E., et al. Oral supplementation of 2′-fucosyllactose during lactation improves memory and learning in rats. J. Nutr. Biochem. 31 (2016), 20–27.
32. 32 Benton, D., et al. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61 (2007), 355–361.
33. 33 Messaoudi, M., 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. 105 (2011), 755–764.
34. 34 Messaoudi, M., et al. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2 (2011), 256–261.
35. 35 Steenbergen, L., et al. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav. Immun. 48 (2015), 258–264.
36. 36 Kato-Kataoka, A., et al. Fermented milk containing Lactobacillus casei strain Shirota preserves the diversity of the gut microbiota and relieves abdominal dysfunction in healthy medical students exposed to academic stress. Appl. Environ. Microbiol. 82 (2016), 3649–3658.
37. 37 Sashihara, T., et al. Effects of Lactobacillus gasseri OLL2809 and α-lactalbumin on university-student athletes: a randomized, double-blind, placebo-controlled clinical trial. Appl. Physiol. Nutr. Metab. 38 (2013), 1228–1235.
38. 38 O'Mahony, L., et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 128 (2005), 541–551.
39. 39 Mayer, E.A., Tillisch, K., The brain–gut axis in abdominal pain syndromes. Annu. Rev. Med. 62 (2011), 381–396.
40. 40 Kassinen, A., et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 133 (2007), 24–33.
41. 41 Clarke, G., et al. Irritable bowel syndrome: towards biomarker identification. Trends Mol. Med. 15 (2009), 478–489.
42. 42 Tillisch, K., et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144 (2013), 1394–1401.
43. 43 Britton, J.C., et al. Facial expressions and complex IAPS pictures: common and differential networks. Neuroimage 31 (2006), 906–919.
44. 44 Schmidt, K., et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl) 232 (2015), 1793–1801.
45. 45 Bhagwagar, Z., et al. Increased salivary cortisol after waking in depression. Psychopharmacology (Berl) 182 (2005), 54–57.
46. 46 Mannie, Z.N., et al. Increased waking salivary cortisol levels in young people at familial risk of depression. Am. J. Psychiatry 164 (2007), 617–621.
47. 47 Beck, A.T., Cognitive Therapy and the Emotional Disorders. 1979, Penguin.
48. 48 Ironside, M., et al. Frontal cortex stimulation reduces vigilance to threat: implications for the treatment of depression and anxiety. Biol. Psychiatry 79 (2016), 823–830.
49. 49 Bercik, P., et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut–brain communication. Neurogastroenterol. Motil. 23 (2011), 1132–1139.
50. 50 Kunze, W.A., et al. Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J. Cell. Mol. Med. 13 (2009), 2261–2270.
51. 51 Ma, X., et al. Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli. Am. J. Physiol. Gastrointest. Liver Physiol. 296 (2009), G868–G875.
52. 52 Cryan, J.F., Dinan, T.G., Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13 (2012), 701–712.
53. 53 McVey Neufeld, et al. The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol. Motil. 25 (2013), 183–188.
54. 54 Collins, J., et al. Intestinal microbiota influence the early postnatal development of the enteric nervous system. Neurogastroenterol. Motil. 26 (2014), 98–107.
55. 55 Lomasney, K.W., et al. Selective influence of host microbiota on cAMP-mediated ion transport in mouse colon. Neurogastroenterol. Motil. 26 (2014), 887–888.
56. 56 Kabouridis, P.S., et al. Microbiota controls the homeostasis of glial cells in the gut lamina propria. Neuron 85 (2015), 289–295.
57. 57 Barrett, E., et al. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J. Appl. Microbiol. 113 (2012), 411–417.
58. 58 Dinan, T.G., et al. Collective unconscious: how gut microbes shape human behavior. J. Psychiatr. Res. 63 (2015), 1–9.
59. 59 Lyte, M., Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. Bioessays 33 (2011), 574–581.
60. 60 Thayer, J.F., Sternberg, E.M., Neural concomitants of immunity: focus on the vagus nerve. Neuroimage 47 (2009), 908–910.
61. 61 de Haan, J.J., et al. Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex. Am. J. Physiol. Gastrointest. Liver Physiol. 305 (2013), G383–G391.
62. 62 Mezzacappa, E.S., et al. Vagal rebound and recovery from psychological stress. Psychosom. Med. 63 (2001), 650–657.
63. 63 Spalding, T.W., et al. Vagal and cardiac reactivity to psychological stressors in trained and untrained men. Med. Sci. Sports Exerc. 32 (2000), 581–591.
64. 64 Borovikova, L.V., et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405 (2000), 458–462.
65. 65 Kirchner, A., et al. Left vagus nerve stimulation suppresses experimentally induced pain. Neurology 55 (2000), 1167–1171.
66. 66 Morris, G.L., Mueller, W.M., Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology 53 (1999), 1731–1735.
67. 67 Sackeim, H.A., et al. Vagus nerve stimulation (VNS™) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology 25 (2001), 713–728.
68. 68 Rush, A.J., et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol. Psychiatry 58 (2005), 347–354.
69. 69 Adinoff, B., et al. Vagal tone decreases following intravenous diazepam. Psychiatry Res. 41 (1992), 89–97.
70. 70 Salam, O.M.A., Fluoxetine and sertraline stimulate gastric acid secretion via a vagal pathway in anaesthetised rats. Pharmacol. Res. 50 (2004), 309–316.
71. 71 Smith, R., et al. Increased association over time between regional frontal lobe BOLD change magnitude and cardiac vagal control with sertraline treatment for major depression. Psychiatry Res. Neuroimag. 224 (2014), 225–233.
72. 72 De Lartigue, G., et al. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin. Physiol. Behav. 105 (2011), 100–105.
73. 73 Bercik, P., et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141 (2011), 599–609.
74. 74 Qin, J., et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464 (2010), 59–65.
75. 75 Horn, T., Klein, J., Neuroprotective effects of lactate in brain ischemia: dependence on anesthetic drugs. Neurochem. Int. 62 (2013), 251–257.
76. 76 Moretti, M., et al. Behavioral and neurochemical effects of sodium butyrate in an animal model of mania. Behav. Pharmacol. 22 (2011), 766–772.
77. 77 Overduin, J., et al. Dietary galacto-oligosaccharides and calcium: effects on energy intake, fat-pad weight and satiety-related, gastrointestinal hormones in rats. Br. J. Nutr. 109 (2013), 1338–1348.
78. 78 Sun, J., et al. Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress. Neurosci. Lett. 618 (2016), 159–166.
79. 79 Stilling, R.M., et al. Microbial genes, brain & behaviour–epigenetic regulation of the gut–brain axis. Genes Brain Behav. 13 (2014), 69–86.
80. 80 Erny, D., et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18 (2015), 965–977.
81. 81 Gagliano, H., et al. High doses of the histone deacetylase inhibitor sodium butyrate trigger a stress-like response. Neuropharmacology 79 (2014), 75–82.
82. 82 Alenghat, T., Artis, D., Epigenomic regulation of host–microbiota interactions. Trends Immunol. 35 (2014), 518–525.
83. 83 Perry, R.J., et al. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature 534 (2016), 213–217.
84. 84 Nøhr, M.K., et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology 154 (2013), 3552–3564.
85. 85 Psichas, A., et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. 39 (2015), 424–429.
86. 86 Cani, P.D., et al. Oligofructose promotes satiety in rats fed a high-fat diet: involvement of glucagon-like peptide-1. Obes. Res. 13 (2005), 1000–1007.
87. 87 Dockray, G.J., Gastrointestinal hormones and the dialogue between gut and brain. J. Physiol. 592 (2014), 2927–2941.
88. 88 Anderberg, R.H., et al. Dopamine signaling in the amygdala, increased by food ingestion and GLP-1, regulates feeding behavior. Physiol. Behav. 136 (2014), 135–144.
89. 89 Stadlbauer, U., et al. PYY 3-36: Beyond food intake. Front. Neuroendocrinol. 38 (2015), 1–11.
90. 90 Morris, G., et al. The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmune disease. Mol. Neurobiol., 2016 Published online June 27, 2016 http://dx.doi.org/10.1007/s12035-016-0004-2.
91. 91 Wikoff, W.R., et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl. Acad. Sci. U.S.A. 106 (2009), 3698–3703.
92. 92 Yano, J.M., et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161 (2015), 264–276.
93. 93 Mackey, D., McFall, A.J., MAMPs and MIMPs: proposed classifications for inducers of innate immunity. Mol. Microbiol. 61 (2006), 1365–1371.
94. 94 Chu, H., Mazmanian, S.K., Innate immune recognition of the microbiota promotes host-microbial symbiosis. Nat. Immunol. 14 (2013), 668–675.
95. 95 Zhou, W., et al. Protective effects of bifidobacteria on intestines in newborn rats with necrotizing enterocolitis and its regulation on TLR2 and TLR4. Genet Mol. Res. 14 (2015), 11505–11514.
96. 96 Bode, L., et al. Inhibition of monocyte, lymphocyte, and neutrophil adhesion to endothelial cells by human milk oligosaccharides. Thromb. Haemost. 92 (2004), 1402–1410.
97. 97 Eiwegger, T., et al. Prebiotic oligosaccharides: in vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties. Pediatr. Allergy Immunol. 21 (2010), 1179–1188.
98. 98 McCusker, R.H., Kelley, K.W., Immune–neural connections: How the immune system's response to infectious agents influences behavior. J. Exp. Biol. 216 (2013), 84–98.
99. 99 Miller, A.H., et al. Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress. Anxiety 30 (2013), 297–306.
100. 100 Felger, J.C., Lotrich, F.E., Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience 246 (2013), 199–229.
101. 101 Louveau, A., et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523 (2015), 337–341.
102. 102 Pessi, T., et al. Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin. Exp. Allergy 30 (2000), 1804–1808.
103. 103 Banks, W.A., Erickson, M.A., The blood–brain barrier and immune function and dysfunction. Neurobiol. Dis. 37 (2010), 26–32.
104. 104 de Vries, H.E., et al. The influence of cytokines on the integrity of the blood–brain barrier in vitro. J. Neuroimmunol. 64 (1996), 37–43.
105. 105 Ek, M., et al. Inflammatory response: pathway across the blood–brain barrier. Nature 410 (2001), 430–431.
106. 106 Bercik, P., et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 139 (2010), 2102–2112.
107. 107 Wang, F., et al. Interferon-γ and tumor necrosis factor-α synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression. Am. J. Pathol. 166 (2005), 409–419.
108. 108 Wang, F., et al. IFN-γ-induced TNFR2 expression is required for TNF-dependent intestinal epithelial barrier dysfunction. Gastroenterology 131 (2006), 1153–1163.
109. 109 Donato, K.A., et al. Lactobacillus rhamnosus GG attenuates interferon-γ and tumour necrosis factor-α-induced barrier dysfunction and pro-inflammatory signalling. Microbiology 156 (2010), 3288–3297.
110. 110 O'Hara, A.M., et al. Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius. Immunology 118 (2006), 202–215.
111. 111 Redhu, N., et al. O-005 YI microbiota drives inflammation by altering intestinal lamina propria macrophage phenotype in a novel IL10R-deficient model of very early onset IBD. Inflamm. Bowe. Dis., 2016, 22.
112. 112 Ray, A., et al. Gut microbial dysbiosis due to helicobacter drives an increase in marginal zone B cells in the absence of IL-10 signaling in macrophages. J. Immunol. 195 (2015), 3071–3085.
113. 113 Kim, K.S., et al. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science 351 (2016), 858–863.
114. 114 Bharwani, A., et al. Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology 63 (2016), 217–227.
115. 115 Söderholm, J.D., Perdue, M.H., II. Stress and intestinal barrier function. Am. J. Physiol. Gastrointest. Liver Physiol. 280 (2001), G7–G13.
116. 116 Santos, J., et al. Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut 48 (2001), 630–636.
117. 117 Mass, M., et al. 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 (2008), 117–124.
118. 118 Maes, M., et al. Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J. Affect. Disord. 141 (2012), 55–62.
119. 119 Ait-Belgnaoui, A., et al. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology 37 (2012), 1885–1895.
120. 120 Zareie, M., et al. Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut 55 (2006), 1553–1560.
121. 121 Romijn, A.R., Rucklidge, J.J., Systematic review of evidence to support the theory of psychobiotics. Nutr. Rev. 73 (2015), 675–693.
122. 122 Forsythe, P., et al. Moody microbes or fecal phrenology: what do we know about the microbiota–gut–brain axis?. BMC Med., 14, 2016, 58.
123. 123 Davey, K.J., et al. Olanzapine induced weight gain in the rat: Impact on inflammatory, metabolic and microbiota parameters. Psychopharmacology (Berl) 221 (2013), 155–169.
124. 124 Davey, K.J., et al. Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl. Psychiatry, 3, 2013, e309.
125. 125 Cho, I., et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488 (2012), 621–626.
126. 126 El Rakaiby, M., et al. Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics. OMICS 18 (2014), 402–414.
127. 127 David, L.A., et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505 (2014), 559–563.
128. 128 Hildebrandt, M.A., et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137 (2009), 1716–1724.
129. 129 Kang, S.S., et al. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol. Neurodegener., 9, 2014, 36.
130. 130 Goldsmith, R.L., et al. Physical fitness as a determinant of vagal modulation. Med. Sci. Sports Exerc. 29 (1997), 812–817.
131. 131 Sugawara, J., et al. Change in post-exercise vagal reactivation with exercise training and detraining in young men. Eur. J. Appl. Physiol. 85 (2001), 259–263.
132. 132 De Filippo, C., et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. U.S.A. 107 (2010), 14691–14696.
133. 133 Fallani, M., et al. Intestinal microbiota of 6-week-old infants across Europe: geographic influence beyond delivery mode, breast-feeding, and antibiotics. J. Pediatr. Gastroenterol. Nutr. 51 (2010), 77–84.
134. 134 Yatsunenko, T., et al. Human gut microbiome viewed across age and geography. Nature 486 (2012), 222–227.
135. 135 Jia, S., et al. Chitosan oligosaccharides alleviate cognitive deficits in an amyloid-β 1-42-induced rat model of Alzheimer disease. Int. J. Biol. Macromol. 83 (2016), 416–425.
136. 136 Song, L., et al. Galactooligosaccharide improves the animal survival and alleviates motor neuron death in SOD1 G93A mouse model of amyotrophic lateral sclerosis. Neuroscience 246 (2013), 281–290.
137. 137 Hsiao, E.Y., et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155 (2013), 1451–1463.
138. 138 Rodrigues, D.M., et al. Probiotics are effective for the prevention and treatment of Citrobacter rodentium–induced colitis in mice. J. Infect. Dis. 206 (2012), 99–109.
139. 139 Gareau, M.G., et al. Probiotics prevent death caused by Citrobacter rodentium infection in neonatal mice. J. Infect. Dis. 201 (2010), 81–91.
140. 140 Mackos, A.R., et al. Probiotic Lactobacillus reuteri attenuates the stressor-enhanced severity of Citrobacter rodentium infection. Infect. Immun. 81 (2013), 3253–3263.
141. 141 Mackos, A.R., et al. Social stress-enhanced severity of Citrobacter rodentium-induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri. Mucosal. Immunol. 9 (2015), 515–526.
142. 142 Davari, S., et al. Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome–gut–brain axis. Neuroscience 240 (2013), 287–296.
143. 143 Marques, T.M., et al. Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model. Benef. Microbes, 2016, 1–12.
144. 144 Luo, J., et al. Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat. Sci. China Life Sci. 57 (2014), 327–335.
145. 145 Savignac, H.M., et al. Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice. Brain Behav. Immun. 52 (2016), 120–131.
146. 146 McNulty, N.P., et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci. Transl. Med., 3, 2011, 106ra106.
147. 147 Kristensen, N.B., et al. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Med., 8, 2016, 52.
148. 148 Claesson, M.J., et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc. Natl. Acad. Sci. U.S.A. 108 (2011), 4586–4591.
149. 149 Claesson, M.J., et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 488 (2012), 178–184.
150. 150 Distrutti, E., et al. Modulation of intestinal microbiota by the probiotic VSL# 3 resets brain gene expression and ameliorates the age-related deficit in LTP. PLoS One, 9, 2014, e106503.
151. 151 Lahtinen, S.J., et al. Probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM® modifies subpopulations of fecal lactobacilli and Clostridium difficile in the elderly. Age 34 (2012), 133–143.
152. 152 Rampelli, S., et al. A probiotics-containing biscuit modulates the intestinal microbiota in the elderly. J. Nutr. Health Aging 17 (2013), 166–172.
153. 153 Savignac, H.M., et al. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol. Motil. 26 (2014), 1615–1627.
154. 154 Savignac, H.M., et al. Bifidobacteria modulate cognitive processes in an anxious mouse strain. Behav. Brain Res. 287 (2015), 59–72.
155. 155 Ohland, C.L., et al. Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology 38 (2013), 1738–1747.