Host–microbiota interactions: epigenomic regulation

Current Opinion in Immunology

Volumn 44, Issue , 2017, Pages 52-60

  Woo, Vivienne ^a   Alenghat, Theresa ^a  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE DEACETYLASE; SHORT CHAIN FATTY ACID; VOLATILE FATTY ACID;

AMEBIASIS; BIFIDOBACTERIUM; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CENTRAL NERVOUS SYSTEM; CLOSTRIDIA; COLON EPITHELIUM; COMMENSAL; COMMENSALISM; ENDOCYTOBIOSIS; ENTAMOEBA HISTOLYTICA; EPIGENETICS; GENE EXPRESSION; GENETIC CODE; HOST CELL; IMMUNE RESPONSE; INTESTINE EPITHELIUM CELL; INTESTINE INNERVATION; MAMMAL; MAMMAL CELL; MICROBIAL GENOME; MICROFLORA; NATURAL HOST; NONHUMAN; REVIEW; ANIMAL; BACTERIUM; GENETIC EPIGENESIS; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOLOGY; METABOLISM; SYMBIOSIS;

ANIMALS; BACTERIA; EPIGENESIS, GENETIC; EPIGENOMICS; FATTY ACIDS, VOLATILE; HISTONE DEACETYLASES; HOST-PATHOGEN INTERACTIONS; HUMANS; MICROBIOTA; SYMBIOSIS;

EID: 85009348377     PISSN: 09527915     EISSN: 18790372     Source Type: Journal    
DOI: 10.1016/j.coi.2016.12.001     Document Type: Review

References (91)

1. 1 Clemente, J.C., Ursell, L.K., Parfrey, L.W., Knight, R., The impact of the gut microbiota on human health: an integrative view. Cell 148 (2012), 1258–1270.
2. 2 Harakeh, S.M., Khan, I., Kumosani, T., Barbour, E., Almasaudi, S.B., Bahijri, S.M., Alfadul, S.M., Ajabnoor, G.M., Azhar, E.I., Gut microbiota: a contributing factor to obesity. Front Cell Infect Microbiol, 6, 2016, 95.
3. 3 Brestoff, J.R., Artis, D., Commensal bacteria at the interface of host metabolism and the immune system. Nat Immunol 14 (2013), 676–684.
4. 4 Kabat, A.M., Srinivasan, N., Maloy, K.J., Modulation of immune development and function by intestinal microbiota. Trends Immunol 35 (2014), 507–517.
5. 5 Kaiko, G.E., Stappenbeck, T.S., Host-microbe interactions shaping the gastrointestinal environment. Trends Immunol 35 (2014), 538–548.
6. 6 Tremaroli, V., Backhed, F., Functional interactions between the gut microbiota and host metabolism. Nature 489 (2012), 242–249.
7. 7 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.
8. 8 Stappenbeck, T.S., Hooper, L.V., Gordon, J.I., Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A 99 (2002), 15451–15455.
9. 9 Cantone, I., Fisher, A.G., Epigenetic programming and reprogramming during development. Nat Struct Mol Biol 20 (2013), 282–289.
10. 10 Sheaffer, K.L., Kim, R., Aoki, R., Elliott, E.N., Schug, J., Burger, L., Schubeler, D., Kaestner, K.H., DNA methylation is required for the control of stem cell differentiation in the small intestine. Genes Dev 28 (2014), 652–664.
11. 11 Avgustinova, A., Benitah, S.A., Epigenetic control of adult stem cell function. Nat Rev Mol Cell Biol, 2016.
12. 12 Berger, S.L., Kouzarides, T., Shiekhattar, R., Shilatifard, A., An operational definition of epigenetics. Genes Dev 23 (2009), 781–783.
13. 13 Arrowsmith, C.H., Bountra, C., Fish, P.V., Lee, K., Schapira, M., Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov 11 (2012), 384–400.
14. 14 Grunstein, M., Histone acetylation in chromatin structure and transcription. Nature 389 (1997), 349–352.
15. 15 Smith, C.L., Peterson, C.L., ATP-dependent chromatin remodeling. Curr Top Dev Biol 65 (2005), 115–148.
16. 16 Jenuwein, T., Allis, C.D., Translating the histone code. Science 293 (2001), 1074–1080.
17. 17 Strahl, B.D., Allis, C.D., The language of covalent histone modifications. Nature 403 (2000), 41–45.
18. 18 Macfarlane, S., Macfarlane, G.T., Regulation of short-chain fatty acid production. Proc Nutr Soc 62 (2003), 67–72.
19. 19 Bolognini, D., Moss, C.E., Nilsson, K., Petersson, A.U., Donnelly, I., Sergeev, E., Konig, G.M., Kostenis, E., Kurowska-Stolarska, M., Miller, A., et al. A novel allosteric activator of free fatty acid 2 receptor displays unique gi-functional bias. J Biol Chem 291 (2016), 18915–18931.
20. 20 Rooks, M.G., Garrett, W.S., Gut microbiota, metabolites and host immunity. Nat Rev Immunol 16 (2016), 341–352.
21. 21 Rivera-Chavez, F., Zhang, L.F., Faber, F., Lopez, C.A., Byndloss, M.X., Olsan, E.E., Xu, G., Velazquez, E.M., Lebrilla, C.B., Winter, S.E., et al. Depletion of butyrate-producing Clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella. Cell Host Microbe 19 (2016), 443–454.
22. 22 Louis, P., Hold, G.L., Flint, H.J., The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 12 (2014), 661–672.
23. 23 Peng, L., He, Z., Chen, W., Holzman, I.R., Lin, J., Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier. Pediatr Res 61 (2007), 37–41.
24. 24 Suzuki, T., Yoshida, S., Hara, H., Physiological concentrations of short-chain fatty acids immediately suppress colonic epithelial permeability. Br J Nutr 100 (2008), 297–305.
25. 25 Maslowski, K.M., Vieira, A.T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H.C., Rolph, M.S., Mackay, F., Artis, D., et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461 (2009), 1282–1286.
26. 26 Macia, L., Tan, J., Vieira, A.T., Leach, K., Stanley, D., Luong, S., Maruya, M., Ian McKenzie, C., Hijikata, A., Wong, C., et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat Commun, 6, 2015, 6734.
27. 27 Kim, M.H., Kang, S.G., Park, J.H., Yanagisawa, M., Kim, C.H., Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology 145 (2013), 396–406 e391-310.
28. 28 Obata, Y., Furusawa, Y., Hase, K., Epigenetic modifications of the immune system in health and disease. Immunol Cell Biol 93 (2015), 226–232.
29. 29 Thaiss, C.A., Zmora, N., Levy, M., Elinav, E., The microbiome and innate immunity. Nature 535 (2016), 65–74.
30. 30 Ganal, S.C., Sanos, S.L., Kallfass, C., Oberle, K., Johner, C., Kirschning, C., Lienenklaus, S., Weiss, S., Staeheli, P., Aichele, P., et al. Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota. Immunity 37 (2012), 171–186.
31. 31 Kobayashi, T., Matsuoka, K., Sheikh, S.Z., Russo, S.M., Mishima, Y., Collins, C., deZoeten, E.F., Karp, C.L., Ting, J.P., Sartor, R.B., et al. IL-10 regulates Il12b expression via histone deacetylation: implications for intestinal macrophage homeostasis. J Immunol 189 (2012), 1792–1799.
32. 32• Chang, P.V., Hao, L., Offermanns, S., Medzhitov, R., The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A 111 (2014), 2247–2252 This study demonstrated that microbiota-derived butyrate regulated histone acetylation and gene expression in intestinal macrophages in a HDAC dependent manner.
33. 33 Abt, M.C., Osborne, L.C., Monticelli, L.A., Doering, T.A., Alenghat, T., Sonnenberg, G.F., Paley, M.A., Antenus, M., Williams, K.L., Erikson, J., et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37 (2012), 158–170.
34. 34 Ji, J., Shu, D., Zheng, M., Wang, J., Luo, C., Wang, Y., Guo, F., Zou, X., Lv, X., Li, Y., et al. Microbial metabolite butyrate facilitates M2 macrophage polarization and function. Sci Rep, 6, 2016, 24838.
35. 35 Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J.R., Pfeffer, K., Coffer, P.J., et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504 (2013), 451–455.
36. 36 Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P.D., Manicassamy, S., Munn, D.H., et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40 (2014), 128–139.
37. 37 Boucard-Jourdin, M., Kugler, D., Endale Ahanda, M.L., This, S., De Calisto, J., Zhang, A., Mora, J.R., Stuart, L.M., Savill, J., Lacy-Hulbert, A., et al. beta8 integrin expression and activation of TGF-beta by intestinal dendritic cells are determined by both tissue microenvironment and cell lineage. J Immunol 197 (2016), 1968–1978.
38. 38 Burgess, S.L., Saleh, M., Cowardin, C.A., Buonomo, E., Noor, Z., Watanabe, K., Abhyankar, M., Lajoie, S., Wills-Karp, M., Petri, W.A. Jr., Role of serum amyloid A, GM-CSF and bone marrow granulocyte-monocyte precursor expansion in segmented filamentous bacteria-mediated protection from Entamoeba histolytica. Infect Immun, 2016.
39. 39 Cella, M., Fuchs, A., Vermi, W., Facchetti, F., Otero, K., Lennerz, J.K., Doherty, J.M., Mills, J.C., Colonna, M., A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457 (2009), 722–725.
40. 40 Sanos, S.L., Bui, V.L., Mortha, A., Oberle, K., Heners, C., Johner, C., Diefenbach, A., RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 10 (2009), 83–91.
41. 41 Satoh-Takayama, N., Vosshenrich, C.A., Lesjean-Pottier, S., Sawa, S., Lochner, M., Rattis, F., Mention, J.J., Thiam, K., Cerf-Bensussan, N., Mandelboim, O., et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29 (2008), 958–970.
42. 42 Sawa, S., Lochner, M., Satoh-Takayama, N., Dulauroy, S., Berard, M., Kleinschek, M., Cua, D., Di Santo, J.P., Eberl, G., RORgammat+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat Immunol 12 (2011), 320–326.
43. 43 Sonnenberg, G.F., Mjosberg, J., Spits, H., Artis D:, SnapShot: Innate Lymphoid Cells. Immunity, 39, 2013 622-622 e621.
44. 44 Eberl, G., Colonna, M., Di Santo, J.P., McKenzie, A.N., Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science, 348, 2015, aaa6566.
45. 45 Artis, D., Spits, H., The biology of innate lymphoid cells. Nature 517 (2015), 293–301.
46. 46 Buonocore, S., Ahern, P.P., Uhlig, H.H., Ivanov, I.I., Littman, D.R., Maloy, K.J., Powrie, F., Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464 (2010), 1371–1375.
47. 47 Zook, E.C., Kee, B.L., Development of innate lymphoid cells. Nat Immunol 17 (2016), 775–782.
48. 48 Serafini, N., Klein Wolterink, R.G., Satoh-Takayama, N., Xu, W., Vosshenrich, C.A., Hendriks, R.W., Di Santo, J.P., Gata3 drives development of RORgammat+ group 3 innate lymphoid cells. J Exp Med 211 (2014), 199–208.
49. 49 Sonnenberg, G.F., Monticelli, L.A., Alenghat, T., Fung, T.C., Hutnick, N.A., Kunisawa, J., Shibata, N., Grunberg, S., Sinha, R., Zahm, A.M., et al. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336 (2012), 1321–1325.
50. 50 Reynders, A., Yessaad, N., Vu Manh, T.P., Dalod, M., Fenis, A., Aubry, C., Nikitas, G., Escaliere, B., Renauld, J.C., Dussurget, O., et al. Identity, regulation and in vivo function of gut NKp46 + RORgammat+ and NKp46 + RORgammat- lymphoid cells. EMBO J 30 (2011), 2934–2947.
51. 51 Sawa, S., Cherrier, M., Lochner, M., Satoh-Takayama, N., Fehling, H.J., Langa, F., Di Santo, J.P., Eberl, G., Lineage relationship analysis of RORgammat+ innate lymphoid cells. Science 330 (2010), 665–669.
52. 52 Lee, J.S., Cella, M., McDonald, K.G., Garlanda, C., Kennedy, G.D., Nukaya, M., Mantovani, A., Kopan, R., Bradfield, C.A., Newberry, R.D., et al. AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat Immunol 13 (2011), 144–151.
53. ••].
54. ••].
55. 55•• Gury-BenAri, M., Thaiss, C.A., Serafini, N., Winter, D.R., Giladi, A., Lara-Astiaso, D., Levy, M., Salame, T.M., Weiner, A., David, E., et al. The spectrum and regulatory landscape of intestinal innate lymphoid cells are shaped by the microbiome. Cell 166 (2016), 1231–1246 e1213 This group of studies combined genome-wide and single-cell transcriptional and epigenomic approaches to demonstrate the influence of the microbiota on the epigenome of ILCs in the mouse and human intestine.
56. 56 Zeissig, S., Blumberg, R.S., Commensal microbial regulation of natural killer T cells at the frontiers of the mucosal immune system. FEBS Lett 588 (2014), 4188–4194.
57. 57 Olszak, T., An, D., Zeissig, S., Vera, M.P., Richter, J., Franke, A., Glickman, J.N., Siebert, R., Baron, R.M., Kasper, D.L., et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336 (2012), 489–493.
58. 58 Tanoue, T., Atarashi, K., Honda, K., Development and maintenance of intestinal regulatory T cells. Nat Rev Immunol 16 (2016), 295–309.
59. 59 Furusawa, Y., Obata, Y., Fukuda, S., Endo, T.A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504 (2013), 446–450.
60. 60 Park, J., Kim, M., Kang, S.G., Jannasch, A.H., Cooper, B., Patterson, J., Kim, C.H., Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol 8 (2015), 80–93.
61. 61 Smith, P.M., Howitt, M.R., Panikov, N., Michaud, M., Gallini, C.A., Bohlooly, Y.M., Glickman, J.N., Garrett, W.S., The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341 (2013), 569–573.
62. 62 Beier, U.H., Wang, L., Han, R., Akimova, T., Liu, Y., Hancock, W.W., Histone deacetylases 6 and 9 and sirtuin-1 control Foxp3+ regulatory T cell function through shared and isoform-specific mechanisms. Sci Signal, 5, 2012, ra45.
63. 63 Wang, L., Liu, Y., Han, R., Beier, U.H., Bhatti, T.R., Akimova, T., Greene, M.I., Hiebert, S.W., Hancock, W.W., FOXP3(+) regulatory T cell development and function require histone/protein deacetylase 3. J Clin Invest, 125, 2015, 3304.
64. 64•• Obata, Y., Furusawa, Y., Endo, T.A., Sharif, J., Takahashi, D., Atarashi, K., Nakayama, M., Onawa, S., Fujimura, Y., Takahashi, M., et al. The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells. Nat Immunol 15 (2014), 571–579 The authors linked the microbiota with expression of the DNA methylation adaptor protein UHRF1 and DNA methylation in colonic Treg cell homeostasis.
65. 65 Gallo, R.L., Hooper, L.V., Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol 12 (2012), 503–516.
66. 66 Peterson, L.W., Artis, D., Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol 14 (2014), 141–153.
67. 67 Hooper, L.V., Wong, M.H., Thelin, A., Hansson, L., Falk, P.G., Gordon, J.I., Molecular analysis of commensal host-microbial relationships in the intestine. Science 291 (2001), 881–884.
68. 68 Larsson, E., Tremaroli, V., Lee, Y.S., Koren, O., Nookaew, I., Fricker, A., Nielsen, J., Ley, R.E., Backhed, F., Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut 61 (2012), 1124–1131.
69. 69 Kernbauer, E., Cadwell, K., Autophagy, viruses, and intestinal immunity. Curr Opin Gastroenterol 30 (2014), 539–546.
70. 70 Atarashi, K., Tanoue, T., Ando, M., Kamada, N., Nagano, Y., Narushima, S., Suda, W., Imaoka, A., Setoyama, H., Nagamori, T., et al. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163 (2015), 367–380.
71. 71 Sommer, F., Nookaew, I., Sommer, N., Fogelstrand, P., Backhed, F., Site-specific programming of the host epithelial transcriptome by the gut microbiota. Genome Biol, 16, 2015, 62.
72. 72 Takahashi, K., Sugi, Y., Nakano, K., Tsuda, M., Kurihara, K., Hosono, A., Kaminogawa, S., Epigenetic control of the host gene by commensal bacteria in large intestinal epithelial cells. J Biol Chem 286 (2011), 35755–35762.
73. 73• Camp, J.G., Frank, C.L., Lickwar, C.R., Guturu, H., Rube, T., Wenger, A.M., Chen, J., Bejerano, G., Crawford, G.E., Rawls, J.F., Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape. Genome Res 24 (2014), 1504–1516 This study suggested that the microbiota does not globally alter chromatin accessibility but instead differentially regulates transcription factors expression and recruitment in IECs.
74. 74 Kraiczy, J., Nayak, K., Ross, A., Raine, T., Mak, T.N., Gasparetto, M., Cario, E., Rakyan, V., Heuschkel, R., Zilbauer, M., Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease. Mucosal Immunol 9 (2016), 647–658.
75. 75 Elliott, E.N., Kaestner, K.H., Epigenetic regulation of the intestinal epithelium. Cell Mol Life Sci 72 (2015), 4139–4156.
76. 76• Yu, D.H., Gadkari, M., Zhou, Q., Yu, S., Gao, N., Guan, Y., Schady, D., Roshan, T.N., Chen, M.H., Laritsky, E., et al. Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome. Genome Biol, 16, 2015, 211 The authors demonstrated a microbiota-dependent DNA methylation patterning in intestinal epithelial cells at genes associated with intestinal development.
77. 77 Elliott, E.N., Sheaffer, K.L., Schug, J., Stappenbeck, T.S., Kaestner, K.H., Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium. Development 142 (2015), 2163–2172.
78. 78 Donohoe, D.R., Garge, N., Zhang, X., Sun, W., O'Connell, T.M., Bunger, M.K., Bultman, S.J., The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab 13 (2011), 517–526.
79. 79• Kaiko, G.E., Ryu, S.H., Koues, O.I., Collins, P.L., Solnica-Krezel, L., Pearce, E.J., Pearce, E.L., Oltz, E.M., Stappenbeck, T.S., The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 165 (2016), 1708–1720 The authors identified that colonic crypt structure protects the intestinal stem cells from butyrate-induced dysregulation of intestinal stem cell function and epithelial development.
80. 80 Alenghat, T., Osborne, L.C., Saenz, S.A., Kobuley, D., Ziegler, C.G., Mullican, S.E., Choi, I., Grunberg, S., Sinha, R., Wynosky-Dolfi, M., et al. Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature 504 (2013), 153–157.
81. 81 Turgeon, N., Gagne, J.M., Blais, M., Gendron, F.P., Boudreau, F., Asselin, C., The acetylome regulators Hdac1 and Hdac2 differently modulate intestinal epithelial cell dependent homeostatic responses in experimental colitis. Am J Physiol Gastrointest Liver Physiol 306 (2014), G594–G605.
82. 82 Zimberlin, C.D., Lancini, C., Sno, R., Rosekrans, S.L., McLean, C.M., Vlaming, H., van den Brink, G.R., Bots, M., Medema, J.P., Dannenberg, J.H., HDAC1 and HDAC2 collectively regulate intestinal stem cell homeostasis. FASEB J 29 (2015), 2070–2080.
83. 83 Gonneaud, A., Turgeon, N., Boudreau, F., Perreault, N., Rivard, N., Asselin, C., Distinct roles for intestinal epithelial cell-specific Hdac1 and Hdac2 in the regulation of murine intestinal homeostasis. J Cell Physiol 231 (2016), 436–448.
84. 84 Carabotti, M., Scirocco, A., Maselli, M.A., Severi, C., The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 28 (2015), 203–209.
85. 85 McVey Neufeld, K.A., Mao, Y.K., Bienenstock, J., Foster, J.A., Kunze, W.A., The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol Motil, 25, 2013 183-e188.
86. 86 Anitha, M., Vijay-Kumar, M., Sitaraman, S.V., Gewirtz, A.T., Srinivasan, S., Gut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling. Gastroenterology 143 (2012), 1006–1016 e1004.
87. 87 Yano, J.M., Yu, K., Donaldson, G.P., Shastri, G.G., Ann, P., Ma, L., Nagler, C.R., Ismagilov, R.F., Mazmanian, S.K., Hsiao, E.Y., Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161 (2015), 264–276.
88. 88 Reigstad, C.S., Salmonson, C.E., Rainey, J.F. 3rd, Szurszewski, J.H., Linden, D.R., Sonnenburg, J.L., Farrugia, G., Kashyap, P.C., Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29 (2015), 1395–1403.
89. 89 Suply, E., de Vries, P., Soret, R., Cossais, F., Neunlist, M., Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon. Am J Physiol Gastrointest Liver Physiol 302 (2012), G1373–G1380.
90. 90 Soret, R., Chevalier, J., De Coppet, P., Poupeau, G., Derkinderen, P., Segain, J.P., Neunlist, M., Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. Gastroenterology 138 (2010), 1772–1782.
91. 91•• Erny, D., Hrabe de Angelis, A.L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18 (2015), 965–977 This study identified a novel role for the microbiota and SCFAs in mediating microglia development and homeostasis in the CNS.