The microbiome: A key regulator of stress and neuroinflammation

Neurobiology of Stress

Volumn 4, Issue , 2016, Pages 23-33

  Rea, Kieran ^a   Dinan, Timothy G ^a,b   Cryan, John F ^a,b  

^a UNIVERSITY COLLEGE CORK   (Ireland)

^b UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

[No Author keywords available]

Indexed keywords

CATECHOLAMINE; CORTICOTROPIN; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 4; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MINERALOCORTICOID; NEUROPEPTIDE; NEUROTRANSMITTER; PATHOGEN ASSOCIATED MOLECULAR PATTERN; PATTERN RECOGNITION RECEPTOR; PEPTIDE YY; PROBIOTIC AGENT; SEROTONIN; TUMOR NECROSIS FACTOR;

ACTINOBACTERIA; ADENOHYPOPHYSIS; ADOLESCENCE; ADOLESCENT BEHAVIOR; ADULTHOOD; AGING; BACILLUS; BACTERIODETES; BEHAVIOR; BIFIDOBACTERIUM; BIOCHEMISTRY; BLAUTIA; BLOOD BRAIN BARRIER; CANDIDA; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL (TOPIC); CORTICOSTERONE RELEASE; DENDRITIC CELL; DISEASE ASSOCIATION; ENTEROCOCCUS; ESCHERICHIA; FIRMICUTES; FUSOBACTERIA; HOMEOSTASIS; HUMAN; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; IMMUNE RESPONSE; IMMUNOSURVEILLANCE; INTESTINE FLORA; LACTOBACILLUS; LACTOBACILLUS FARCIMINIS; LACTOBACILLUS HELVETICUS; LONG TERM POTENTIATION; NERVOUS SYSTEM INFLAMMATION; NEUROENDOCRINE SYSTEM; NEUROMODULATION; NONHUMAN; ORGANISMAL INTERACTION; PRIORITY JOURNAL; PROTEOBACTERIA; REVIEW; SACCHAROMYCES; STRESS; SYNAPTIC MEMBRANE; VERRUCOMICROBIA;

EID: 84960432592     PISSN: None     EISSN: 23522895     Source Type: Journal    
DOI: 10.1016/j.ynstr.2016.03.001     Document Type: Review

References (186)

1. Ait-Belgnaoui, A., Durand, H., Cartier, C., Chaumaz, G., Eutamene, H., Ferrier, L., Houdeau, E., Fioramonti, J., Bueno, L., Theodorou, V., Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology 37:11 (2012), 1885–1895.
2. Alboni, S., Maggi, L., Editorial: cytokines as players of neuronal plasticity and sensitivity to environment in healthy and pathological brain. Front. Cell Neurosci., 9, 2015, 508.
3. Allez, M., Tieng, V., Nakazawa, A., Treton, X., Pacault, V., Dulphy, N., Caillat-Zucman, S., Paul, P., Gornet, J.M., Douay, C., Ravet, S., Tamouza, R., Charron, D., Lemann, M., Mayer, L., Toubert, A., CD4+NKG2D+ T cells in Crohn's disease mediate inflammatory and cytotoxic responses through MICA interactions. Gastroenterology 132:7 (2007), 2346–2358.
4. Aspelund, A., Antila, S., Proulx, S.T., Karlsen, T.V., Karaman, S., Detmar, M., Wiig, H., Alitalo, K., A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 212:7 (2015), 991–999.
5. Bachstetter, A.D., Van Eldik, L.J., Schmitt, F.A., Neltner, J.H., Ighodaro, E.T., Webster, S.J., Patel, E., Abner, E.L., Kryscio, R.J., Nelson, P.T., Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging. Acta Neuropathol. Commun., 3, 2015, 32.
6. Bailey, M.T., Influence of stressor-induced nervous system activation on the intestinal microbiota and the importance for immunomodulation. Adv. Exp. Med. Biol. 817 (2014), 255–276.
7. Bailey, M.T., Dowd, S.E., Galley, J.D., Hufnagle, A.R., Allen, R.G., Lyte, M., Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav. Immun. 25:3 (2011), 397–407.
8. Barouei, J., Moussavi, M., Hodgson, D.M., Effect of maternal probiotic intervention on HPA axis, immunity and gut microbiota in a rat model of irritable bowel syndrome. PLoS One, 7(10), 2012, e46051.
9. Beattie, E.C., Stellwagen, D., Morishita, W., Bresnahan, J.C., Ha, B.K., Von Zastrow, M., Beattie, M.S., Malenka, R.C., Control of synaptic strength by glial TNFalpha. Science 295:5563 (2002), 2282–2285.
10. Beijers, R., Jansen, J., Riksen-Walraven, M., de Weerth, C., Maternal prenatal anxiety and stress predict infant illnesses and health complaints. Pediatrics 126:2 (2010), e401–e409.
11. Belkaid, Y., Naik, S., Compartmentalized and systemic control of tissue immunity by commensals. Nat. Immunol. 14:7 (2013), 646–653.
12. Bellavance, M.A., Rivest, S., The HPA - immune Axis and the immunomodulatory actions of glucocorticoids in the brain. Front. Immunol., 5, 2014, 136.
13. Bellavance, M.A., Rivest, S., The neuroendocrine control of the innate immune system in health and brain diseases. Immunol. Rev. 248:1 (2012), 36–55.
14. Bengmark, S., Gut microbiota, immune development and function. Pharmacol. Res. 69:1 (2013), 87–113.
15. Bharwani, A., Mian, M.F., Foster, J.A., Surette, M.G., Bienenstock, J., Forsythe, P., Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology 63 (2015), 217–227.
16. Biagi, E., Candela, M., Fairweather-Tait, S., Franceschi, C., Brigidi, P., Aging of the human metaorganism: the microbial counterpart. Age (Dordr) 34:1 (2012), 247–267.
17. Biagi, E., Nylund, L., Candela, M., Ostan, R., Bucci, L., Pini, E., Nikkila, J., Monti, D., Satokari, R., Franceschi, C., Brigidi, P., De Vos, W., Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One, 5(5), 2010, e10667.
18. Bilbo, S.D., Schwarz, J.M., Early-life programming of later-life brain and behavior: a critical role for the immune system. Front. Behav. Neurosci., 3, 2009, 14.
19. Bilbo, S.D., Schwarz, J.M., The immune system and developmental programming of brain and behavior. Front. Neuroendocrinol. 33:3 (2012), 267–286.
20. Bilimoria, P.M., Stevens, B., Microglia function during brain development: new insights from animal models. Brain Res. 1617 (2015), 7–17.
21. Blandino, P. Jr., Hueston, C.M., Barnum, C.J., Bishop, C., Deak, T., The impact of ventral noradrenergic bundle lesions on increased IL-1 in the PVN and hormonal responses to stress in male sprague dawley rats. Endocrinology 154:7 (2013), 2489–2500.
22. Borre, Y.E., Moloney, R.D., Clarke, G., Dinan, T.G., Cryan, J.F., The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. Adv. Exp. Med. Biol. 817 (2014), 373–403.
23. Borre, Y.E., O'Keeffe, G.W., Clarke, G., Stanton, C., Dinan, T.G., Cryan, J.F., Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol. Med. 20:9 (2014), 509–518.
24. Braniste, V., Al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., Toth, M., Korecka, A., Bakocevic, N., Ng, L.G., Kundu, P., Gulyas, B., Halldin, C., Hultenby, K., Nilsson, H., Hebert, H., Volpe, B.T., Diamond, B., Pettersson, S., The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med., 6(263), 2014 263ra158.
25. Bravo, J.A., Forsythe, P., Chew, M.V., Escaravage, E., Savignac, H.M., Dinan, T.G., Bienenstock, J., Cryan, J.F., 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. 108:38 (2011), 16050–16055.
26. Burnett, S., Sebastian, C., Cohen Kadosh, K., Blakemore, S.J., The social brain in adolescence: evidence from functional magnetic resonance imaging and behavioural studies. Neurosci. Biobehav Rev. 35:8 (2011), 1654–1664.
27. Burokas, A., Moloney, R.D., Arboleya, S., Stanton, C., Dinan, T.G., Cryan, J., Targeting the microbiota-gut-brain axis with prebiotics in mice: a novel strategy for stress-related disorders. Poster Session Presented at 45th Annual Conference for Society for Neuroscience, Oct 17-21, Washington, DC, USA, 2015.
28. Burokas, A., Moloney, R.D., Dinan, T.G., Cryan, J.F., Microbiota regulation of the Mammalian gut-brain axis. Adv. Appl. Microbiol. 91 (2015), 1–62.
29. Cani, P.D., Everard, A., Duparc, T., Gut microbiota, enteroendocrine functions and metabolism. Curr. Opin. Pharmacol. 13:6 (2013), 935–940.
30. Capuron, L., Miller, A.H., Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol. Ther. 130:2 (2011), 226–238.
31. Cassel, S.L., Sutterwala, F.S., Flavell, R.A., The tiny conductor: immune regulation via commensal organisms. Cell Host Microbe 3:6 (2008), 340–341.
32. Charo, I.F., Ransohoff, R.M., The many roles of chemokines and chemokine receptors in inflammation. N. Engl. J. Med. 354:6 (2006), 610–621.
33. Clarke, G., Cryan, J.F., Dinan, T.G., Quigley, E.M., Review article: probiotics for the treatment of irritable bowel syndrome–focus on lactic acid bacteria. Aliment. Pharmacol. Ther. 35:4 (2012), 403–413.
34. Clarke, G., Grenham, S., Scully, P., Fitzgerald, P., Moloney, R.D., Shanahan, F., Dinan, T.G., Cryan, J.F., The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol. Psychiatry 18:6 (2013), 666–673.
35. Collins, S.M., Surette, M., Bercik, P., The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol. 10:11 (2012), 735–742.
36. Crumeyrolle-Arias, M., Jaglin, M., Bruneau, A., Vancassel, S., Cardona, A., Dauge, V., Naudon, L., Rabot, S., Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology 42 (2014), 207–217.
37. Cryan, J.F., Dinan, T.G., Gut microbiota: microbiota and neuroimmune signalling-Metchnikoff to microglia. Nat. Rev. Gastroenterol. Hepatol. 12:9 (2015), 494–496.
38. Cryan, J.F., Dinan, T.G., Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13:10 (2012), 701–712.
39. Cryan, J.F., Dinan, T.G., More than a gut feeling: the microbiota regulates neurodevelopment and behavior. Neuropsychopharmacology 40:1 (2015), 241–242.
40. Cummings, J.H., Macfarlane, G.T., Role of intestinal bacteria in nutrient metabolism. JPEN J. Parenter. Enter. Nutr. 21:6 (1997), 357–365.
41. D'Mello, C., Le, T., Swain, M.G., Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. J. Neurosci. 29:7 (2009), 2089–2102.
42. D'Mello, C., Ronaghan, N., Zaheer, R., Dicay, M., Le, T., MacNaughton, W.K., Surrette, M.G., Swain, M.G., Probiotics improve inflammation-associated sickness behavior by altering communication between the peripheral immune system and the brain. J. Neurosci. 35:30 (2015), 10821–10830.
43. Dahl, R.E., Adolescent brain development: a period of vulnerabilities and opportunities. Keynote address. Ann. N. Y. Acad. Sci. 1021 (2004), 1–22.
44. Dallman, M.F., Akana, S.F., Levin, N., Walker, C.D., Bradbury, M.J., Suemaru, S., Scribner, K.S., Corticosteroids and the control of function in the hypothalamo-pituitary-adrenal (HPA) axis. Ann. N. Y. Acad. Sci. 746 (1994), 22–31 discussion 31-2, 64-7.
45. De Kloet, E.R., Oitzl, M.S., Schobitz, B., Cytokines and the brain corticosteroid receptor balance: relevance to pathophysiology of neuroendocrine-immune communication. Psychoneuroendocrinology 19:2 (1994), 121–134.
46. De Palma, G., Blennerhassett, P., Lu, J., Deng, Y., Park, A.J., Green, W., Denou, E., Silva, M.A., Santacruz, A., Sanz, Y., Surette, M.G., Verdu, E.F., Collins, S.M., Bercik, P., Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nat. Commun., 6, 2015, 7735.
47. De Palma, G., Collins, S.M., Bercik, P., Verdu, E.F., The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both?. J. Physiol. 592:Pt 14 (2014), 2989–2997.
48. Delpech, J.C., Madore, C., Nadjar, A., Joffre, C., Wohleb, E.S., Laye, S., Microglia in neuronal plasticity: influence of stress. Neuropharmacology 96:Pt A (2015), 19–28.
49. Desbonnet, L., Clarke, G., O'Sullivan, O., Cotter, P.D., Dinan, T.G., Cryan, J.F., Re: gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav. Immun. 50 (2015), 335–336.
50. Desbonnet, L., Clarke, G., Traplin, A., O'Sullivan, O., Crispie, F., Moloney, R.D., Cotter, P.D., Dinan, T.G., Cryan, J.F., Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav. Immun. 48 (2015), 165–173.
51. Desbonnet, L., Garrett, L., Clarke, G., Kiely, B., Cryan, J.F., Dinan, T.G., Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 170:4 (2010), 1179–1188.
52. Dickmeis, T., Weger, B.D., Weger, M., The circadian clock and glucocorticoids–interactions across many time scales. Mol. Cell Endocrinol. 380:1–2 (2013), 2–15.
53. Dinan, T.G., Cryan, J., Shanahan, F., Keeling, P.W., Quigley, E.M., IBS: an epigenetic perspective. Nat. Rev. Gastroenterol. Hepatol. 7:8 (2010), 465–471.
54. Dinan, T.G., Cryan, J.F., Regulation of the stress response by the gut microbiota: implications for psychoneuroendocrinology. Psychoneuroendocrinology 37:9 (2012), 1369–1378.
55. Dinan, T.G., Stilling, R.M., Stanton, C., Cryan, J.F., Collective unconscious: how gut microbes shape human behavior. J. Psychiatr. Res. 63 (2015), 1–9.
56. Dorrestein, P.C., Mazmanian, S.K., Knight, R., Finding the missing links among metabolites, microbes, and the host. Immunity 40:6 (2014), 824–832.
57. Duerkop, B.A., Vaishnava, S., Hooper, L.V., Immune responses to the microbiota at the intestinal mucosal surface. Immunity 31:3 (2009), 368–376.
58. Eckburg, P.B., Bik, E.M., Bernstein, C.N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S.R., Nelson, K.E., Relman, D.A., Diversity of the human intestinal microbial flora. Science 308:5728 (2005), 1635–1638.
59. El Aidy, S., Dinan, T.G., Cryan, J.F., Gut microbiota: the conductor in the orchestra of immune-neuroendocrine communication. Clin. Ther. 37:5 (2015), 954–967.
60. El Aidy, S., Dinan, T.G., Cryan, J.F., Immune modulation of the brain-gut-microbe axis. Front. Microbiol., 5, 2014, 146.
61. Elsenbruch, S., Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms. Brain Behav. Immun. 25:3 (2011), 386–394.
62. Erny, D., Hrabe de Angelis, A.L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., Schwierzeck, V., Utermohlen, O., Chun, E., Garrett, W.S., McCoy, K.D., Diefenbach, A., Staeheli, P., Stecher, B., Amit, I., Prinz, M., Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18:7 (2015), 965–977.
63. Eskandari, F., Webster, J.I., Sternberg, E.M., Neural immune pathways and their connection to inflammatory diseases. Arthritis Res. Ther. 5:6 (2003), 251–265.
64. Farhadi, A., Banan, A., Fields, J., Keshavarzian, A., Intestinal barrier: an interface between health and disease. J. Gastroenterol. Hepatol. 18:5 (2003), 479–497.
65. Fasano, A., Shea-Donohue, T., Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat. Clin. Pract. Gastroenterol. Hepatol. 2:9 (2005), 416–422.
66. Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M.P., Invidia, L., Celani, L., Scurti, M., Cevenini, E., Castellani, G.C., Salvioli, S., Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128:1 (2007), 92–105.
67. Frank, D.N., Pace, N.R., Gastrointestinal microbiology enters the metagenomics era. Curr. Opin. Gastroenterol. 24:1 (2008), 4–10.
68. Frank, M.G., Baratta, M.V., Sprunger, D.B., Watkins, L.R., Maier, S.F., Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav. Immun. 21:1 (2007), 47–59.
69. Frank, M.G., Thompson, B.M., Watkins, L.R., Maier, S.F., Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses. Brain Behav. Immun. 26:2 (2012), 337–345.
70. Gaci, N., Borrel, G., Tottey, W., O'Toole, P.W., Brugere, J.F., Archaea and the human gut: new beginning of an old story. World J. Gastroenterol. 20:43 (2014), 16062–16078.
71. Ganguly, P., Brenhouse, H.C., Broken or maladaptive? Altered trajectories in neuroinflammation and behavior after early life adversity. Dev. Cogn. Neurosci. 11 (2015), 18–30.
72. Gareau, M.G., Jury, J., MacQueen, G., Sherman, P.M., Perdue, M.H., Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut 56:11 (2007), 1522–1528.
73. Gevers, D., Kugathasan, S., Denson, L.A., Vazquez-Baeza, Y., Van Treuren, W., Ren, B., Schwager, E., Knights, D., Song, S.J., Yassour, M., Morgan, X.C., Kostic, A.D., Luo, C., Gonzalez, A., McDonald, D., Haberman, Y., Walters, T., Baker, S., Rosh, J., Stephens, M., Heyman, M., Markowitz, J., Baldassano, R., Griffiths, A., Sylvester, F., Mack, D., Kim, S., Crandall, W., Hyams, J., Huttenhower, C., Knight, R., Xavier, R.J., The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 15:3 (2014), 382–392.
74. Golubeva, A.V., Crampton, S., Desbonnet, L., Edge, D., O'Sullivan, O., Lomasney, K.W., Zhdanov, A.V., Crispie, F., Moloney, R.D., Borre, Y.E., Cotter, P.D., Hyland, N.P., O'Halloran, K.D., Dinan, T.G., O'Keeffe, G.W., Cryan, J.F., Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood. Psychoneuroendocrinology 60 (2015), 58–74.
75. Hinwood, M., Morandini, J., Day, T.A., Walker, F.R., Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex. Cereb. Cortex 22:6 (2012), 1442–1454.
76. Hinwood, M., Tynan, R.J., Charnley, J.L., Beynon, S.B., Day, T.A., Walker, F.R., Chronic stress induced remodeling of the prefrontal cortex: structural re-organization of microglia and the inhibitory effect of minocycline. Cereb. Cortex 23:8 (2013), 1784–1797.
77. Hodes, G.E., Kana, V., Menard, C., Merad, M., Russo, S.J., Neuroimmune mechanisms of depression. Nat. Neurosci. 18:10 (2015), 1386–1393.
78. Hong, S., Dissing-Olesen, L., Stevens, B., New insights on the role of microglia in synaptic pruning in health and disease. Curr. Opin. Neurobiol. 36 (2016), 128–134.
79. Howell, M.P., Muglia, L.J., Effects of genetically altered brain glucocorticoid receptor action on behavior and adrenal axis regulation in mice. Front. Neuroendocrinol. 27:3 (2006), 275–284.
80. Hsiao, E.Y., McBride, S.W., Hsien, S., Sharon, G., Hyde, E.R., McCue, T., Codelli, J.A., Chow, J., Reisman, S.E., Petrosino, J.F., Patterson, P.H., Mazmanian, S.K., Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155:7 (2013), 1451–1463.
81. Human Microbiome Project, C., Structure, function and diversity of the healthy human microbiome. Nature 486:7402 (2012), 207–214.
82. Hyland, N.P., O'Mahony, S.M., O'Malley, D., O'Mahony, C.M., Dinan, T.G., Cryan, J.F., Early-life stress selectively affects gastrointestinal but not behavioral responses in a genetic model of brain-gut axis dysfunction. Neurogastroenterol. Motil. 27:1 (2015), 105–113.
83. Ivanov, A.I., Naydenov, N.G., Dynamics and regulation of epithelial adherens junctions: recent discoveries and controversies. Int. Rev. Cell Mol. Biol. 303 (2013), 27–99.
84. Jara, L.J., Navarro, C., Medina, G., Vera-Lastra, O., Blanco, F., Immune-neuroendocrine interactions and autoimmune diseases. Clin. Dev. Immunol. 13:2–4 (2006), 109–123.
85. Jeffery, I.B., Quigley, E.M., Ohman, L., Simren, M., O'Toole, P.W., The microbiota link to irritable bowel syndrome: an emerging story. Gut Microbes 3:6 (2012), 572–576.
86. Johnson, J.D., Campisi, J., Sharkey, C.M., Kennedy, S.L., Nickerson, M., Greenwood, B.N., Fleshner, M., Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines. Neuroscience 135:4 (2005), 1295–1307.
87. Kamada, N., Seo, S.U., Chen, G.Y., Nunez, G., Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol. 13:5 (2013), 321–335.
88. Kasubuchi, M., Hasegawa, S., Hiramatsu, T., Ichimura, A., Kimura, I., Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients 7:4 (2015), 2839–2849.
89. Kelly, J.R., Kennedy, P.J., Cryan, J.F., Dinan, T.G., Clarke, G., Hyland, N.P., Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell Neurosci., 9, 2015, 392.
90. Kettenmann, H., Hanisch, U.K., Noda, M., Verkhratsky, A., Physiology of microglia. Physiol. Rev. 91:2 (2011), 461–553.
91. Kim, H.S., Suh, Y.H., Minocycline and neurodegenerative diseases. Behav. Brain Res. 196:2 (2009), 168–179.
92. Kim, S.U., de Vellis, J., Microglia in health and disease. J. Neurosci. Res. 81:3 (2005), 302–313.
93. Kleiman, A., Tuckermann, J.P., Glucocorticoid receptor action in beneficial and side effects of steroid therapy: lessons from conditional knockout mice. Mol. Cell Endocrinol. 275:1–2 (2007), 98–108.
94. Kreisel, T., Frank, M.G., Licht, T., Reshef, R., Ben-Menachem-Zidon, O., Baratta, M.V., Maier, S.F., Yirmiya, R., Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis. Mol. Psychiatry 19:6 (2014), 699–709.
95. Kunis, G., Baruch, K., Rosenzweig, N., Kertser, A., Miller, O., Berkutzki, T., Schwartz, M., IFN-gamma-dependent activation of the brain's choroid plexus for CNS immune surveillance and repair. Brain 136:Pt 11 (2013), 3427–3440.
96. Kurokawa, K., Itoh, T., Kuwahara, T., Oshima, K., Toh, H., Toyoda, A., Takami, H., Morita, H., Sharma, V.K., Srivastava, T.P., Taylor, T.D., Noguchi, H., Mori, H., Ogura, Y., Ehrlich, D.S., Itoh, K., Takagi, T., Sakaki, Y., Hayashi, T., Hattori, M., Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res. 14:4 (2007), 169–181.
97. Ley, R.E., Hamady, M., Lozupone, C., Turnbaugh, P.J., Ramey, R.R., Bircher, J.S., Schlegel, M.L., Tucker, T.A., Schrenzel, M.D., Knight, R., Gordon, J.I., Evolution of mammals and their gut microbes. Science 320:5883 (2008), 1647–1651.
98. Lightman, S.L., The neuroendocrinology of stress: a never ending story. J. Neuroendocrinol. 20:6 (2008), 880–884.
99. Louveau, A., Smirnov, I., Keyes, T.J., Eccles, J.D., Rouhani, S.J., Peske, J.D., Derecki, N.C., Castle, D., Mandell, J.W., Lee, K.S., Harris, T.H., Kipnis, J., Structural and functional features of central nervous system lymphatic vessels. Nature 523:7560 (2015), 337–341.
100. Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K., Knight, R., Diversity, stability and resilience of the human gut microbiota. Nature 489:7415 (2012), 220–230.
101. Lyte, M., Microbial endocrinology and the microbiota-gut-brain axis. Adv. Exp. Med. Biol. 817 (2014), 3–24.
102. Lyte, M., Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS Pathog., 9(11), 2013, e1003726.
103. Madara, J.L., Regulation of the movement of solutes across tight junctions. Annu. Rev. Physiol. 60 (1998), 143–159.
104. Mastorakos, G., Ilias, I., Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress. Ann. N. Y. Acad. Sci. 1088 (2006), 373–381.
105. Mastorakos, G., Ilias, I., Relationship between interleukin-6 (IL-6) and hypothalamic-pituitary-adrenal axis hormones in rheumatoid arthritis. Z Rheumatol., 59(Suppl. 2), 2000 II/75–9.
106. Matsuo, K., Zhang, X., Ono, Y., Nagatomi, R., Acute stress-induced colonic tissue HSP70 expression requires commensal bacterial components and intrinsic glucocorticoid. Brain Behav. Immun. 23:1 (2009), 108–115.
107. Mayer, E.A., The neurobiology of stress and gastrointestinal disease. Gut 47:6 (2000), 861–869.
108. Mayer, E.A., Knight, R., Mazmanian, S.K., Cryan, J.F., Tillisch, K., Gut microbes and the brain: paradigm shift in neuroscience. J. Neurosci. 34:46 (2014), 15490–15496.
109. Mayer, E.A., Tillisch, K., Gupta, A., Gut/brain axis and the microbiota. J. Clin. Invest 125:3 (2015), 926–938.
110. Mazmanian, S.K., Liu, C.H., Tzianabos, A.O., Kasper, D.L., An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122:1 (2005), 107–118.
111. McEwen, B.S., Gray, J.D., Nasca, C., 60 YEARS OF NEUROENDOCRINOLOGY: redefining neuroendocrinology: stress, sex and cognitive and emotional regulation. J. Endocrinol. 226:2 (2015), T67–T83.
112. McKernan, D.P., Fitzgerald, P., Dinan, T.G., Cryan, J.F., The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat. Neurogastroenterol. Motil., 22(9), 2010 1029–35, e268.
113. Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A., Bisson, J.F., Rougeot, C., Pichelin, M., Cazaubiel, M., Cazaubiel, J.M., Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br. J. Nutr. 105:5 (2011), 755–764.
114. Messaoudi, M., Violle, N., Bisson, J.F., Desor, D., Javelot, H., Rougeot, C., Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2:4 (2011), 256–261.
115. Miller, A.H., Neuroendocrine and immune system interactions in stress and depression. Psychiatr. Clin. North Am. 21:2 (1998), 443–463.
116. Moloney, R.D., Desbonnet, L., Clarke, G., Dinan, T.G., Cryan, J.F., The microbiome: stress, health and disease. Mamm. Genome 25:1–2 (2014), 49–74.
117. Moloney, R.D., O'Leary, O.F., Felice, D., Bettler, B., Dinan, T.G., Cryan, J.F., Early-life stress induces visceral hypersensitivity in mice. Neurosci. Lett. 512:2 (2012), 99–102.
118. Mulla, A., Buckingham, J.C., Regulation of the hypothalamo-pituitary-adrenal axis by cytokines. Baillieres Best. Pract. Res. Clin. Endocrinol. Metab. 13:4 (1999), 503–521.
119. Nayak, D., Zinselmeyer, B.H., Corps, K.N., McGavern, D.B., In vivo dynamics of innate immune sentinels in the CNS. Intravital 1:2 (2012), 95–106.
120. Neufeld, K.A., Kang, N., Bienenstock, J., Foster, J.A., Effects of intestinal microbiota on anxiety-like behavior. Commun. Integr. Biol. 4:4 (2011), 492–494.
121. Neufeld, K.M., Kang, N., Bienenstock, J., Foster, J.A., Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol. Motil., 23(3), 2011 255–64, e119.
122. Nilsson, N.E., Kotarsky, K., Owman, C., Olde, B., Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem. Biophys. Res. Commun. 303:4 (2003), 1047–1052.
123. Nishino, R., Mikami, K., Takahashi, H., Tomonaga, S., Furuse, M., Hiramoto, T., Aiba, Y., Koga, Y., Sudo, N., Commensal microbiota modulate murine behaviors in a strictly contamination-free environment confirmed by culture-based methods. Neurogastroenterol. Motil. 25:6 (2013), 521–528.
124. O'Connor, R.M., Cryan, J.F., Adolescent brain vulnerability and psychopathology through the generations: role of diet and dopamine. Biol. Psychiatry 75:1 (2014), 4–6.
125. O'Mahony, S.M., Clarke, G., Dinan, T.G., Cryan, J.F., Early-life adversity and brain development: is the microbiome a missing piece of the puzzle?. Neuroscience, 2015.
126. O'Mahony, S.M., Felice, V.D., Nally, K., Savignac, H.M., Claesson, M.J., Scully, P., Woznicki, J., Hyland, N.P., Shanahan, F., Quigley, E.M., Marchesi, J.R., O'Toole, P.W., Dinan, T.G., Cryan, J.F., Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience 277 (2014), 885–901.
127. Palmer, C., Bik, E.M., DiGiulio, D.B., Relman, D.A., Brown, P.O., Development of the human infant intestinal microbiota. PLoS Biol., 5(7), 2007, e177.
128. Palomar, M.M., Maldonado Galdeano, C., Perdigon, G., Influence of a probiotic lactobacillus strain on the intestinal ecosystem in a stress model mouse. Brain Behav. Immun. 35 (2014), 77–85.
129. Paolicelli, R.C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T.A., Guiducci, E., Dumas, L., Ragozzino, D., Gross, C.T., Synaptic pruning by microglia is necessary for normal brain development. Science 333:6048 (2011), 1456–1458.
130. Petanjek, Z., Judas, M., Simic, G., Rasin, M.R., Uylings, H.B., Rakic, P., Kostovic, I., Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc. Natl. Acad. Sci. U. S. A. 108:32 (2011), 13281–13286.
131. Pitossi, F., del Rey, A., Kabiersch, A., Besedovsky, H., Induction of cytokine transcripts in the central nervous system and pituitary following peripheral administration of endotoxin to mice. J. Neurosci. Res. 48:4 (1997), 287–298.
132. Pocock, J.M., Kettenmann, H., Neurotransmitter receptors on microglia. Trends Neurosci. 30:10 (2007), 527–535.
133. Pott, J., Hornef, M., Innate immune signalling at the intestinal epithelium in homeostasis and disease. EMBO Rep. 13:8 (2012), 684–698.
134. Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K.S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., Mende, D.R., Li, J., Xu, J., Li, S., Li, D., Cao, J., Wang, B., Liang, H., Zheng, H., Xie, Y., Tap, J., Lepage, P., Bertalan, M., Batto, J.M., Hansen, T., Le Paslier, D., Linneberg, A., Nielsen, H.B., Pelletier, E., Renault, P., Sicheritz-Ponten, T., Turner, K., Zhu, H., Yu, C., Li, S., Jian, M., Zhou, Y., Li, Y., Zhang, X., Li, S., Qin, N., Yang, H., Wang, J., Brunak, S., Dore, J., Guarner, F., Kristiansen, K., Pedersen, O., Parkhill, J., Weissenbach, J., Meta, H.I.T.C., Bork, P., Ehrlich, S.D., Wang, J., A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:7285 (2010), 59–65.
135. Rajilic-Stojanovic, M., Heilig, H.G., Tims, S., Zoetendal, E.G., de Vos, W.M., Long-term monitoring of the human intestinal microbiota composition. Environ. Microbiol., 2012.
136. Rakic, P., Bourgeois, J.P., Eckenhoff, M.F., Zecevic, N., Goldman-Rakic, P.S., Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 232:4747 (1986), 232–235.
137. Rakic, P., Bourgeois, J.P., Goldman-Rakic, P.S., Synaptic development of the cerebral cortex: implications for learning, memory, and mental illness. Prog. Brain Res. 102 (1994), 227–243.
138. Rakic, P.T., The importance of being well placed and having the right connections. Ann. N. Y. Acad. Sci. 882 (1999), 90–106 discussion 128–34.
139. Ransohoff, R.M., Engelhardt, B., The anatomical and cellular basis of immune surveillance in the central nervous system. Nat. Rev. Immunol. 12:9 (2012), 623–635.
140. Ransohoff, R.M., Schafer, D., Vincent, A., Blachere, N.E., Bar-Or, A., Neuroinflammation: ways in which the immune system affects the brain. Neurotherapeutics, 2015.
141. Raznahan, A., Shaw, P., Lalonde, F., Stockman, M., Wallace, G.L., Greenstein, D., Clasen, L., Gogtay, N., Giedd, J.N., How does your cortex grow?. J. Neurosci. 31:19 (2011), 7174–7177.
142. Reber, S.O., Peters, S., Slattery, D.A., Hofmann, C., Scholmerich, J., Neumann, I.D., Obermeier, F., Mucosal immunosuppression and epithelial barrier defects are key events in murine psychosocial stress-induced colitis. Brain Behav. Immun. 25:6 (2011), 1153–1161.
143. Rhee, S.H., Pothoulakis, C., Mayer, E.A., Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat. Rev. Gastroenterol. Hepatol. 6:5 (2009), 306–314.
144. Rosas-Ballina, M., Tracey, K.J., Cholinergic control of inflammation. J. Intern Med. 265:6 (2009), 663–679.
145. Round, J.L., Mazmanian, S.K., The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9:5 (2009), 313–323.
146. Royet, J., Gupta, D., Dziarski, R., Peptidoglycan recognition proteins: modulators of the microbiome and inflammation. Nat. Rev. Immunol. 11:12 (2011), 837–851.
147. Russell, W.R., Hoyles, L., Flint, H.J., Dumas, M.E., Colonic bacterial metabolites and human health. Curr. Opin. Microbiol. 16:3 (2013), 246–254.
148. Sampson, T.R., Mazmanian, S.K., Control of brain development, function, and behavior by the microbiome. Cell Host Microbe 17:5 (2015), 565–576.
149. Savastano, S., Tommaselli, A.P., Valentino, R., Scarpitta, M.T., D'Amore, G., Luciano, A., Covelli, V., Lombardi, G., Hypothalamic-pituitary-adrenal axis and immune system. Acta Neurol. (Napoli) 16:4 (1994), 206–213.
150. Savignac, H.M., Couch, Y., Stratford, M., Bannerman, D.M., Tzortzis, G., Anthony, D.C., Burnet, P.W., Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL-1-beta levels in male mice. Brain Behav. Immun., 2015.
151. Savignac, H.M., Kiely, B., Dinan, T.G., Cryan, J.F., Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol. Motil. 26:11 (2014), 1615–1627.
152. Scarpellini, E., Ianiro, G., Attili, F., Bassanelli, C., De Santis, A., Gasbarrini, A., The human gut microbiota and virome: potential therapeutic implications. Dig. Liver Dis., 2015.
153. Schafer, D.P., Lehrman, E.K., Kautzman, A.G., Koyama, R., Mardinly, A.R., Yamasaki, R., Ransohoff, R.M., Greenberg, M.E., Barres, B.A., Stevens, B., Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:4 (2012), 691–705.
154. Schafer, D.P., Lehrman, E.K., Stevens, B., The “quad-partite” synapse: microglia-synapse interactions in the developing and mature CNS. Glia 61:1 (2013), 24–36.
155. Schafer, D.P., Stevens, B., Microglia function in Central nervous system development and plasticity. Cold Spring Harb. Perspect. Biol., 2015.
156. Schmidt, K., Cowen, P.J., Harmer, C.J., Tzortzis, G., Errington, S., Burnet, P.W., Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacol. Berl. 232:10 (2015), 1793–1801.
157. Shankar, V., Homer, D., Rigsbee, L., Khamis, H.J., Michail, S., Raymer, M., Reo, N.V., Paliy, O., The networks of human gut microbe-metabolite associations are different between health and irritable bowel syndrome. ISME J. 9:8 (2015), 1899–1903.
158. Sierra, A., Gottfried-Blackmore, A., Milner, T.A., McEwen, B.S., Bulloch, K., Steroid hormone receptor expression and function in microglia. Glia 56:6 (2008), 659–674.
159. Smith, S.M., Vale, W.W., The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin. Neurosci. 8:4 (2006), 383–395.
160. Souza, D.G., Vieira, A.T., Soares, A.C., Pinho, V., Nicoli, J.R., Vieira, L.Q., Teixeira, M.M., The essential role of the intestinal microbiota in facilitating acute inflammatory responses. J. Immunol. 173:6 (2004), 4137–4146.
161. Sowell, E.R., Thompson, P.M., Holmes, C.J., Jernigan, T.L., Toga, A.W., In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nat. Neurosci. 2:10 (1999), 859–861.
162. Sowell, E.R., Thompson, P.M., Tessner, K.D., Toga, A.W., Mapping continued brain growth and gray matter density reduction in dorsal frontal cortex: inverse relationships during postadolescent brain maturation. J. Neurosci. 21:22 (2001), 8819–8829.
163. Sowell, E.R., Thompson, P.M., Toga, A.W., Mapping changes in the human cortex throughout the span of life. Neuroscientist 10:4 (2004), 372–392.
164. Spear, L.P., Adolescent brain development and animal models. Ann. N. Y. Acad. Sci. 1021 (2004), 23–26.
165. Steenbergen, L., Sellaro, R., van Hemert, S., Bosch, J.A., Colzato, L.S., A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav. Immun. 48 (2015), 258–264.
166. Sudo, N., Role of microbiome in regulating the HPA axis and its relevance to allergy. Chem. Immunol. Allergy 98 (2012), 163–175.
167. Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X.N., Kubo, C., Koga, Y., Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 558:Pt 1 (2004), 263–275.
168. Takeda, K., Akira, S., Microbial recognition by Toll-like receptors. J. Dermatol Sci. 34:2 (2004), 73–82.
169. Tikka, T.M., Koistinaho, J.E., Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia. J. Immunol. 166:12 (2001), 7527–7533.
170. Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., Guyonnet, D., Legrain-Raspaud, S., Trotin, B., Naliboff, B., Mayer, E.A., Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144:7 (2013), 1394–1401 1401 e1–4.
171. Tracey, K.J., Physiology and immunology of the cholinergic antiinflammatory pathway. J. Clin. Invest 117:2 (2007), 289–296.
172. Tramullas, M., Finger, B.C., Moloney, R.D., Golubeva, A.V., Moloney, G., Dinan, T.G., Cryan, J.F., Toll-like receptor 4 regulates chronic stress-induced visceral pain in mice. Biol. Psychiatry 76:4 (2014), 340–348.
173. Tremblay, M.E., Stevens, B., Sierra, A., Wake, H., Bessis, A., Nimmerjahn, A., The role of microglia in the healthy brain. J. Neurosci. 31:45 (2011), 16064–16069.
174. Tsigos, C., Chrousos, G.P., Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J. Psychosom. Res. 53:4 (2002), 865–871.
175. Turrin, N.P., Rivest, S., Unraveling the molecular details involved in the intimate link between the immune and neuroendocrine systems. Exp. Biol. Med. (Maywood) 229:10 (2004), 996–1006.
176. Tynan, R.J., Naicker, S., Hinwood, M., Nalivaiko, E., Buller, K.M., Pow, D.V., Day, T.A., Walker, F.R., Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions. Brain Behav. Immun. 24:7 (2010), 1058–1068.
177. Vaishnava, S., Behrendt, C.L., Hooper, L.V., Innate immune responses to commensal bacteria in the gut epithelium. J. Pediatr. Gastroenterol. Nutr. 1:46 Suppl (2008), E10–E11.
178. Vaishnava, S., Behrendt, C.L., Ismail, A.S., Eckmann, L., Hooper, L.V., Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc. Natl. Acad. Sci. U. S. A. 105:52 (2008), 20858–20863.
179. Verma, S., Nakaoke, R., Dohgu, S., Banks, W.A., Release of cytokines by brain endothelial cells: a polarized response to lipopolysaccharide. Brain Behav. Immun. 20:5 (2006), 449–455.
180. von Bernhardi, R., Eugenin-Von Bernhardi, L., Eugenin, J., Microglial cell dysregulation in brain aging and neurodegeneration. Front. Aging Neurosci., 7, 2015, 124.
181. Wilder, R.L., Neuroendocrine-immune system interactions and autoimmunity. Annu. Rev. Immunol. 13 (1995), 307–338.
182. Williamson, L.L., McKenney, E.A., Holzknecht, Z.E., Belliveau, C., Rawls, J.F., Poulton, S., Parker, W., Bilbo, S.D., Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection. Brain Behav. Immun., 2015.
183. Wohleb, E.S., McKim, D.B., Shea, D.T., Powell, N.D., Tarr, A.J., Sheridan, J.F., Godbout, J.P., Re-establishment of anxiety in stress-sensitized mice is caused by monocyte trafficking from the spleen to the brain. Biol. Psychiatry 75:12 (2014), 970–981.
184. Wohleb, E.S., McKim, D.B., Sheridan, J.F., Godbout, J.P., Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior. Front. Neurosci., 8, 2014, 447.
185. Wohleb, E.S., Powell, N.D., Godbout, J.P., Sheridan, J.F., Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior. J. Neurosci. 33:34 (2013), 13820–13833.
186. Yamasaki, R., Lu, H., Butovsky, O., Ohno, N., Rietsch, A.M., Cialic, R., Wu, P.M., Doykan, C.E., Lin, J., Cotleur, A.C., Kidd, G., Zorlu, M.M., Sun, N., Hu, W., Liu, L., Lee, J.C., Taylor, S.E., Uehlein, L., Dixon, D., Gu, J., Floruta, C.M., Zhu, M., Charo, I.F., Weiner, H.L., Ransohoff, R.M., Differential roles of microglia and monocytes in the inflamed central nervous system. J. Exp. Med. 211:8 (2014), 1533–1549.