1932

Abstract

The gastrointestinal tract harbors numerous commensal bacteria, referred to as the microbiota, that benefit host health by digesting dietary components and eliminating pathogens. The intestinal microbiota maintains epithelial barrier integrity and shapes the mucosal immune system, balancing host defense and oral tolerance with microbial metabolites, components, and attachment to host cells. To avoid aberrant immune responses, epithelial cells segregate the intestinal microbiota from immune cells by constructing chemical and physical barriers, leading to the establishment of host-commensal mutualism. Furthermore, intestinal immune cells participate in the maintenance of a healthy microbiota community and reinforce epithelial barrier functions. Perturbations of the microbiota composition are commonly observed in patients with autoimmune diseases and chronic inflammatory disorders. An understanding of the intimate interactions between the intestinal microbiota, epithelial cells, and immune cells that are crucial for the maintenance of intestinal homeostasis might promote advances in diagnostic and therapeutic approaches for various diseases.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-070119-115104
2020-04-26
2024-06-22
Loading full text...

Full text loading...

/deliver/fulltext/immunol/38/1/annurev-immunol-070119-115104.html?itemId=/content/journals/10.1146/annurev-immunol-070119-115104&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Berg RD. 1996. The indigenous gastrointestinal microflora. Trends Microbiol 4:430–35
    [Google Scholar]
  2. 2. 
    Underhill DM, Iliev ID. 2014. The mycobiota: interactions between commensal fungi and the host immune system. Nat. Rev. Immunol. 14:405–16
    [Google Scholar]
  3. 3. 
    Iliev ID, Leonardi I. 2017. Fungal dysbiosis: immunity and interactions at mucosal barriers. Nat. Rev. Immunol. 17:635–46
    [Google Scholar]
  4. 4. 
    Norman JM, Handley SA, Baldridge MT, Droit L, Liu CY et al. 2015. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160:447–60
    [Google Scholar]
  5. 5. 
    Virgin HW. 2014. The virome in mammalian physiology and disease. Cell 157:142–50
    [Google Scholar]
  6. 6. 
    Neil JA, Cadwell K. 2018. The intestinal virome and immunity. J. Immunol. 201:1615–24
    [Google Scholar]
  7. 7. 
    Cadwell K. 2015. The virome in host health and disease. Immunity 42:805–13
    [Google Scholar]
  8. 8. 
    Mani S, Boelsterli UA, Redinbo MR 2014. Understanding and modulating mammalian-microbial communication for improved human health. Annu. Rev. Pharmacol. Toxicol. 54:559–80
    [Google Scholar]
  9. 9. 
    Maynard CL, Elson CO, Hatton RD, Weaver CT 2012. Reciprocal interactions of the intestinal microbiota and immune system. Nature 489:231–41
    [Google Scholar]
  10. 10. 
    Round JL, Mazmanian SK. 2009. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9:313–23
    [Google Scholar]
  11. 11. 
    Honda K, Littman DR. 2012. The microbiome in infectious disease and inflammation. Annu. Rev. Immunol. 30:759–95
    [Google Scholar]
  12. 12. 
    Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT 2005. Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol. Rev. 206:260–76
    [Google Scholar]
  13. 13. 
    Peterson LW, Artis D. 2014. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14:141–53
    [Google Scholar]
  14. 14. 
    Johansson ME, Sjovall H, Hansson GC 2013. The gastrointestinal mucus system in health and disease. Nat. Rev. Gastroenterol. Hepatol. 10:352–61
    [Google Scholar]
  15. 15. 
    Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F 2016. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165:1332–45
    [Google Scholar]
  16. 16. 
    Marchix J, Goddard G, Helmrath MA 2018. Host-gut microbiota crosstalk in intestinal adaptation. Cell Mol. Gastroenterol. Hepatol. 6:149–62
    [Google Scholar]
  17. 17. 
    Hass R, Busche R, Luciano L, Reale E, Engelhardt WV 1997. Lack of butyrate is associated with induction of Bax and subsequent apoptosis in the proximal colon of guinea pig. Gastroenterology 112:875–81
    [Google Scholar]
  18. 18. 
    Frankel WL, Zhang W, Singh A, Klurfeld DM, Don S et al. 1994. Mediation of the trophic effects of short-chain fatty acids on the rat jejunum and colon. Gastroenterology 106:375–80
    [Google Scholar]
  19. 19. 
    Venkatraman A, Ramakrishna BS, Shaji RV, Kumar NS, Pulimood A, Patra S 2003. Amelioration of dextran sulfate colitis by butyrate: role of heat shock protein 70 and NF-κB. Am. J. Physiol. Gastrointest. Liver Physiol. 285:G177–84
    [Google Scholar]
  20. 20. 
    Ahmad MS, Krishnan S, Ramakrishna BS, Mathan M, Pulimood AB, Murthy SN 2000. Butyrate and glucose metabolism by colonocytes in experimental colitis in mice. Gut 46:493–99
    [Google Scholar]
  21. 21. 
    Kim MH, Kang SG, Park JH, Yanagisawa M, Kim CH 2013. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology 145:396–406.e10
    [Google Scholar]
  22. 22. 
    Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R et al. 2014. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40:128–39
    [Google Scholar]
  23. 23. 
    Dupaul-Chicoine J, Yeretssian G, Doiron K, Bergstrom KS, McIntire CR et al. 2010. Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 32:367–78
    [Google Scholar]
  24. 24. 
    Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA et al. 2011. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145:745–57
    [Google Scholar]
  25. 25. 
    Byndloss MX, Olsan EE, Rivera-Chavez F, Tiffany CR, Cevallos SA et al. 2017. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science 357:570–75
    [Google Scholar]
  26. 26. 
    Finnie IA, Dwarakanath AD, Taylor BA, Rhodes JM 1995. Colonic mucin synthesis is increased by sodium butyrate. Gut 36:93–99
    [Google Scholar]
  27. 27. 
    Burger-van Paassen N, Vincent A, Puiman PJ, van der Sluis M, Bouma J et al. 2009. The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection. Biochem. J. 420:211–19
    [Google Scholar]
  28. 28. 
    von Moltke J, Ji M, Liang HE, Locksley RM 2016. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529:221–25
    [Google Scholar]
  29. 29. 
    Nadjsombati MS, McGinty JW, Lyons-Cohen MR, Jaffe JB, DiPeso L et al. 2018. Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit. Immunity 49:33–41.e7
    [Google Scholar]
  30. 30. 
    Guo C, Xie S, Chi Z, Zhang J, Liu Y et al. 2016. Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome. Immunity 45:802–16
    [Google Scholar]
  31. 31. 
    de Aguiar Vallim TQ, Tarling EJ, Edwards PA 2013. Pleiotropic roles of bile acids in metabolism. Cell Metab 17:657–69
    [Google Scholar]
  32. 32. 
    Halpern MD, Holubec H, Saunders TA, Dvorak K, Clark JA et al. 2006. Bile acids induce ileal damage during experimental necrotizing enterocolitis. Gastroenterology 130:359–72
    [Google Scholar]
  33. 33. 
    Mroz MS, Lajczak NK, Goggins BJ, Keely S, Keely SJ 2018. The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing. Am. J. Physiol. Gastrointest. Liver Physiol. 314:G378–87
    [Google Scholar]
  34. 34. 
    Maran RR, Thomas A, Roth M, Sheng Z, Esterly N et al. 2009. Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J. Pharmacol. Exp. Ther. 328:469–77
    [Google Scholar]
  35. 35. 
    Golden JM, Escobar OH, Nguyen MVL, Mallicote MU, Kavarian P et al. 2018. Ursodeoxycholic acid protects against intestinal barrier breakdown by promoting enterocyte migration via EGFR- and COX-2-dependent mechanisms. Am. J. Physiol. Gastrointest. Liver Physiol. 315:G259–71
    [Google Scholar]
  36. 36. 
    Alemi F, Poole DP, Chiu J, Schoonjans K, Cattaruzza F et al. 2013. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology 144:145–54
    [Google Scholar]
  37. 37. 
    Hubbard TD, Murray IA, Perdew GH 2015. Indole and tryptophan metabolism: endogenous and dietary routes to Ah receptor activation. Drug Metab. Dispos. 43:1522–35
    [Google Scholar]
  38. 38. 
    Metidji A, Omenetti S, Crotta S, Li Y, Nye E et al. 2018. The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity. Immunity 49:353–62.e5 Correction. 2019 Immunity 50:1542
    [Google Scholar]
  39. 39. 
    Shimada Y, Kinoshita M, Harada K, Mizutani M, Masahata K et al. 2013. Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon. PLOS ONE 8:e80604
    [Google Scholar]
  40. 40. 
    Venkatesh M, Mukherjee S, Wang H, Li H, Sun K et al. 2014. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41:296–310
    [Google Scholar]
  41. 41. 
    Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ 2000. Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1:113–18
    [Google Scholar]
  42. 42. 
    Vaishnava S, Yamamoto M, Severson KM, Ruhn KA, Yu X et al. 2011. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334:255–58
    [Google Scholar]
  43. 43. 
    Frantz AL, Rogier EW, Weber CR, Shen L, Cohen DA et al. 2012. Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides. Mucosal Immunol 5:501–12
    [Google Scholar]
  44. 44. 
    Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara JL 2001. Cutting edge: Bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J. Immunol. 167:1882–85
    [Google Scholar]
  45. 45. 
    Birchenough GM, Nystrom EE, Johansson ME, Hansson GC 2016. A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science 352:1535–42
    [Google Scholar]
  46. 46. 
    Biswas A, Liu YJ, Hao L, Mizoguchi A, Salzman NH et al. 2010. Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum. PNAS 107:14739–44
    [Google Scholar]
  47. 47. 
    Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP et al. 2014. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156:1045–59
    [Google Scholar]
  48. 48. 
    Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y et al. 2015. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:367–80
    [Google Scholar]
  49. 49. 
    Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–98
    [Google Scholar]
  50. 50. 
    Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K et al. 2006. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 203:2271–79
    [Google Scholar]
  51. 51. 
    Sano T, Huang W, Hall JA, Yang Y, Chen A et al. 2015. An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell 163:381–93
    [Google Scholar]
  52. 52. 
    Price AE, Shamardani K, Lugo KA, Deguine J, Roberts AW et al. 2018. A map of Toll-like receptor expression in the intestinal epithelium reveals distinct spatial, cell type-specific, and temporal patterns. Immunity 49:560–75.e6
    [Google Scholar]
  53. 53. 
    Yount NY, Bayer AS, Xiong YQ, Yeaman MR 2006. Advances in antimicrobial peptide immunobiology. Biopolymers 84:435–58
    [Google Scholar]
  54. 54. 
    Brogden KA. 2005. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat. Rev. Microbiol. 3:238–50
    [Google Scholar]
  55. 55. 
    Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS et al. 1999. Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286:113–17
    [Google Scholar]
  56. 56. 
    Selsted ME, Ouellette AJ. 2005. Mammalian defensins in the antimicrobial immune response. Nat. Immunol. 6:551–57
    [Google Scholar]
  57. 57. 
    Iimura M, Gallo RL, Hase K, Miyamoto Y, Eckmann L, Kagnoff MF 2005. Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J. Immunol. 174:4901–7
    [Google Scholar]
  58. 58. 
    Lehotzky RE, Partch CL, Mukherjee S, Cash HL, Goldman WE et al. 2010. Molecular basis for peptidoglycan recognition by a bactericidal lectin. PNAS 107:7722–27
    [Google Scholar]
  59. 59. 
    Cash HL, Whitham CV, Behrendt CL, Hooper LV 2006. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313:1126–30
    [Google Scholar]
  60. 60. 
    Mukherjee S, Zheng H, Derebe MG, Callenberg KM, Partch CL et al. 2014. Antibacterial membrane attack by a pore-forming intestinal C-type lectin. Nature 505:103–7
    [Google Scholar]
  61. 61. 
    Bhinder G, Stahl M, Sham HP, Crowley SM, Morampudi V et al. 2014. Intestinal epithelium-specific MyD88 signaling impacts host susceptibility to infectious colitis by promoting protective goblet cell and antimicrobial responses. Infect. Immun. 82:3753–63
    [Google Scholar]
  62. 62. 
    Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA 2008. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29:947–57
    [Google Scholar]
  63. 63. 
    Nenci A, Becker C, Wullaert A, Gareus R, van Loo G et al. 2007. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446:557–61
    [Google Scholar]
  64. 64. 
    Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC 2008. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. PNAS 105:15064–69
    [Google Scholar]
  65. 65. 
    Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J et al. 2014. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158:1000–10
    [Google Scholar]
  66. 66. 
    Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J et al. 2010. Enteric defensins are essential regulators of intestinal microbial ecology. Nat. Immunol. 11:76–83
    [Google Scholar]
  67. 67. 
    Cunliffe RN, Mahida YR. 2004. Expression and regulation of antimicrobial peptides in the gastrointestinal tract. J. Leukoc. Biol. 75:49–58
    [Google Scholar]
  68. 68. 
    Yanagibashi T, Hosono A, Oyama A, Tsuda M, Suzuki A et al. 2013. IgA production in the large intestine is modulated by a different mechanism than in the small intestine: Bacteroides acidifaciens promotes IgA production in the large intestine by inducing germinal center formation and increasing the number of IgA+ B cells. Immunobiology 218:645–51
    [Google Scholar]
  69. 69. 
    Okumura R, Kurakawa T, Nakano T, Kayama H, Kinoshita M et al. 2016. Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. Nature 532:117–21
    [Google Scholar]
  70. 70. 
    van Putten JPM, Strijbis K 2017. Transmembrane mucins: signaling receptors at the intersection of inflammation and cancer. J. Innate Immun. 9:281–99
    [Google Scholar]
  71. 71. 
    McGuckin MA, Every AL, Skene CD, Linden SK, Chionh YT et al. 2007. Muc1 mucin limits both Helicobacter pylori colonization of the murine gastric mucosa and associated gastritis. Gastroenterology 133:1210–18
    [Google Scholar]
  72. 72. 
    McAuley JL, Linden SK, Png CW, King RM, Pennington HL et al. 2007. MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J. Clin. Investig. 117:2313–24
    [Google Scholar]
  73. 73. 
    Linden SK, Sheng YH, Every AL, Miles KM, Skoog EC et al. 2009. MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy. PLOS Pathog 5:e1000617
    [Google Scholar]
  74. 74. 
    Zhou C, Liu Z, Liu Y, Fu W, Ding X et al. 2013. Gene silencing of porcine MUC13 and ITGB5: candidate genes towards Escherichia coli F4ac adhesion. PLOS ONE 8:e70303
    [Google Scholar]
  75. 75. 
    Resta-Lenert S, Das S, Batra SK, Ho SB 2011. Muc17 protects intestinal epithelial cells from enteroinvasive E. coli infection by promoting epithelial barrier integrity. Am. J. Physiol. Gastrointest. Liver Physiol. 300:G1144–55
    [Google Scholar]
  76. 76. 
    McGovern DP, Jones MR, Taylor KD, Marciante K, Yan X et al. 2010. Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. Hum. Mol. Genet. 19:3468–76
    [Google Scholar]
  77. 77. 
    Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II et al. 2014. Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Science 345:1254009
    [Google Scholar]
  78. 78. 
    Furuse M. 2010. Molecular basis of the core structure of tight junctions. Cold Spring Harb. Perspect. Biol. 2:a002907
    [Google Scholar]
  79. 79. 
    Garcia-Hernandez V, Quiros M, Nusrat A 2017. Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation. Ann. N. Y. Acad. Sci. 1397:66–79
    [Google Scholar]
  80. 80. 
    Holmes JL, Van Itallie CM, Rasmussen JE, Anderson JM 2006. Claudin profiling in the mouse during postnatal intestinal development and along the gastrointestinal tract reveals complex expression patterns. Gene Expr. Patterns 6:581–88
    [Google Scholar]
  81. 81. 
    Tamura A, Kitano Y, Hata M, Katsuno T, Moriwaki K et al. 2008. Megaintestine in claudin-15-deficient mice. Gastroenterology 134:523–34
    [Google Scholar]
  82. 82. 
    Muto S, Hata M, Taniguchi J, Tsuruoka S, Moriwaki K et al. 2010. Claudin-2-deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules. PNAS 107:8011–16
    [Google Scholar]
  83. 83. 
    Ding L, Lu Z, Foreman O, Tatum R, Lu Q et al. 2012. Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice. Gastroenterology 142:305–15
    [Google Scholar]
  84. 84. 
    Klose CS, Artis D. 2016. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat. Immunol. 17:765–74
    [Google Scholar]
  85. 85. 
    Joeris T, Muller-Luda K, Agace WW, Mowat AM 2017. Diversity and functions of intestinal mononuclear phagocytes. Mucosal Immunol 10:845–64
    [Google Scholar]
  86. 86. 
    Sakaguchi S, Miyara M, Costantino CM, Hafler DA 2010. FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol. 10:490–500
    [Google Scholar]
  87. 87. 
    Rooks MG, Garrett WS. 2016. Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol. 16:341–52
    [Google Scholar]
  88. 88. 
    Tanoue T, Atarashi K, Honda K 2016. Development and maintenance of intestinal regulatory T cells. Nat. Rev. Immunol. 16:295–309
    [Google Scholar]
  89. 89. 
    Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–73
    [Google Scholar]
  90. 90. 
    Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J et al. 2013. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504:451–55
    [Google Scholar]
  91. 91. 
    Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–50
    [Google Scholar]
  92. 92. 
    Chang PV, Hao L, Offermanns S, Medzhitov R 2014. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. PNAS 111:2247–52
    [Google Scholar]
  93. 93. 
    Singh N, Thangaraju M, Prasad PD, Martin PM, Lambert NA et al. 2010. Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J. Biol. Chem. 285:27601–8
    [Google Scholar]
  94. 94. 
    Park J, Kim M, Kang SG, Jannasch AH, Cooper B et al. 2015. 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 8:80–93
    [Google Scholar]
  95. 95. 
    Sun M, Wu W, Chen L, Yang W, Huang X et al. 2018. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat. Commun. 9:3555
    [Google Scholar]
  96. 96. 
    Jost T, Lacroix C, Braegger CP, Chassard C 2012. New insights in gut microbiota establishment in healthy breast fed neonates. PLOS ONE 7:e44595
    [Google Scholar]
  97. 97. 
    Iatsenko I, Boquete JP, Lemaitre B 2018. Microbiota-derived lactate activates production of reactive oxygen species by the intestinal NADPH oxidase Nox and shortens Drosophila lifespan. Immunity 49:929–42.e5
    [Google Scholar]
  98. 98. 
    Okada T, Fukuda S, Hase K, Nishiumi S, Izumi Y et al. 2013. Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice. Nat. Commun. 4:1654
    [Google Scholar]
  99. 99. 
    Lee YS, Kim TY, Kim Y, Lee SH, Kim S et al. 2018. Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development. Cell Host Microbe 24:833–46.e6
    [Google Scholar]
  100. 100. 
    Morita N, Umemoto E, Fujita S, Hayashi A, Kikuta J et al. 2019. GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites. Nature 566:110–14
    [Google Scholar]
  101. 101. 
    Pols TW, Nomura M, Harach T, Lo Sasso G, Oosterveer MH et al. 2011. TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading. Cell Metab 14:747–57
    [Google Scholar]
  102. 102. 
    Biagioli M, Carino A, Cipriani S, Francisci D, Marchiano S et al. 2017. The bile acid receptor GPBAR1 regulates the M1/M2 phenotype of intestinal macrophages and activation of GPBAR1 rescues mice from murine colitis. J. Immunol. 199:718–33
    [Google Scholar]
  103. 103. 
    Vavassori P, Mencarelli A, Renga B, Distrutti E, Fiorucci S 2009. The bile acid receptor FXR is a modulator of intestinal innate immunity. J. Immunol. 183:6251–61
    [Google Scholar]
  104. 104. 
    Keitel V, Reinehr R, Gatsios P, Rupprecht C, Gorg B et al. 2007. The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells. Hepatology 45:695–704
    [Google Scholar]
  105. 105. 
    Olszak T, An D, Zeissig S, Vera MP, Richter J et al. 2012. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336:489–93
    [Google Scholar]
  106. 106. 
    Ramesh R, Kozhaya L, McKevitt K, Djuretic IM, Carlson TJ et al. 2014. Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. J. Exp. Med. 211:89–104
    [Google Scholar]
  107. 107. 
    Cao W, Kayama H, Chen ML, Delmas A, Sun A et al. 2017. The xenobiotic transporter Mdr1 enforces T cell homeostasis in the presence of intestinal bile acids. Immunity 47:1182–96.e10
    [Google Scholar]
  108. 108. 
    Annese V, Valvano MR, Palmieri O, Latiano A, Bossa F, Andriulli A 2006. Multidrug resistance 1 gene in inflammatory bowel disease: a meta-analysis. World J. Gastroenterol. 12:3636–44
    [Google Scholar]
  109. 109. 
    Panwala CM, Jones JC, Viney JL 1998. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J. Immunol. 161:5733–44
    [Google Scholar]
  110. 110. 
    Hironaka I, Iwase T, Sugimoto S, Okuda K, Tajima A et al. 2013. Glucose triggers ATP secretion from bacteria in a growth-phase-dependent manner. Appl. Environ. Microbiol. 79:2328–35
    [Google Scholar]
  111. 111. 
    Mempin R, Tran H, Chen C, Gong H, Kim Ho K, Lu S 2013. Release of extracellular ATP by bacteria during growth. BMC Microbiol 13:301
    [Google Scholar]
  112. 112. 
    Iwase T, Shinji H, Tajima A, Sato F, Tamura T et al. 2010. Isolation and identification of ATP-secreting bacteria from mice and humans. J. Clin. Microbiol. 48:1949–51
    [Google Scholar]
  113. 113. 
    Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M et al. 2008. ATP drives lamina propria TH17 cell differentiation. Nature 455:808–12
    [Google Scholar]
  114. 114. 
    Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A et al. 2007. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110:1225–32
    [Google Scholar]
  115. 115. 
    Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A et al. 2007. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204:1257–65
    [Google Scholar]
  116. 116. 
    Corriden R, Chen Y, Inoue Y, Beldi G, Robson SC et al. 2008. Ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1/CD39) regulates neutrophil chemotaxis by hydrolyzing released ATP to adenosine. J. Biol. Chem. 283:28480–86
    [Google Scholar]
  117. 117. 
    Kukulski F, Bahrami F, Ben Yebdri F, Lecka J, Martin-Satue M et al. 2011. NTPDase1 controls IL-8 production by human neutrophils. J. Immunol. 187:644–53
    [Google Scholar]
  118. 118. 
    Levesque SA, Kukulski F, Enjyoji K, Robson SC, Sevigny J 2010. NTPDase1 governs P2X7-dependent functions in murine macrophages. Eur. J. Immunol. 40:1473–85
    [Google Scholar]
  119. 119. 
    Friedman DJ, Kunzli BM, A-Rahim YI, Sevigny J, Berberat PO et al. 2009. CD39 deletion exacerbates experimental murine colitis and human polymorphisms increase susceptibility to inflammatory bowel disease. PNAS 106:16788–93
    [Google Scholar]
  120. 120. 
    Kusu T, Kayama H, Kinoshita M, Jeon SG, Ueda Y et al. 2013. Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine. J. Immunol. 190:774–83
    [Google Scholar]
  121. 121. 
    Stefan C, Jansen S, Bollen M 2006. Modulation of purinergic signaling by NPP-type ectophosphodiesterases. Purinergic Signal 2:361–70
    [Google Scholar]
  122. 122. 
    Stefan C, Jansen S, Bollen M 2005. NPP-type ectophosphodiesterases: unity in diversity. Trends Biochem. Sci. 30:542–50
    [Google Scholar]
  123. 123. 
    Furuta Y, Tsai SH, Kinoshita M, Fujimoto K, Okumura R et al. 2017. E-NPP3 controls plasmacytoid dendritic cell numbers in the small intestine. PLOS ONE 12:e0172509
    [Google Scholar]
  124. 124. 
    Tsai SH, Kinoshita M, Kusu T, Kayama H, Okumura R et al. 2015. The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells. Immunity 42:279–93
    [Google Scholar]
  125. 125. 
    Kurashima Y, Amiya T, Nochi T, Fujisawa K, Haraguchi T et al. 2012. Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors. Nat. Commun. 3:1034
    [Google Scholar]
  126. 126. 
    Varol C, Zigmond E, Jung S 2010. Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria. Nat. Rev. Immunol. 10:415–26
    [Google Scholar]
  127. 127. 
    Diehl GE, Longman RS, Zhang JX, Breart B, Galan C et al. 2013. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX3CR1hi cells. Nature 494:116–20
    [Google Scholar]
  128. 128. 
    Ueda Y, Kayama H, Jeon SG, Kusu T, Isaka Y et al. 2010. Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10. Int. Immunol. 22:953–62
    [Google Scholar]
  129. 129. 
    Hayashi A, Sato T, Kamada N, Mikami Y, Matsuoka K et al. 2013. A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice. Cell Host Microbe 13:711–22
    [Google Scholar]
  130. 130. 
    Uematsu S, Jang MH, Chevrier N, Guo Z, Kumagai Y et al. 2006. Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells. Nat. Immunol. 7:868–74
    [Google Scholar]
  131. 131. 
    Uematsu S, Akira S. 2009. Immune responses of TLR5+ lamina propria dendritic cells in enterobacterial infection. J. Gastroenterol. 44:803–11
    [Google Scholar]
  132. 132. 
    Franchi L, Amer A, Body-Malapel M, Kanneganti TD, Ozoren N et al. 2006. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages. Nat. Immunol. 7:576–82
    [Google Scholar]
  133. 133. 
    Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P et al. 2012. NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat. Immunol. 13:449–56
    [Google Scholar]
  134. 134. 
    Miao EA, Leaf IA, Treuting PM, Mao DP, Dors M et al. 2010. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat. Immunol. 11:1136–42
    [Google Scholar]
  135. 135. 
    Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K et al. 2008. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity 29:261–71
    [Google Scholar]
  136. 136. 
    Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, Littman DR 2004. An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells. Nat. Immunol. 5:64–73
    [Google Scholar]
  137. 137. 
    Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ et al. 2008. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat. Immunol. 9:769–76
    [Google Scholar]
  138. 138. 
    Mora JR, Iwata M, Eksteen B, Song SY, Junt T et al. 2006. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314:1157–60
    [Google Scholar]
  139. 139. 
    Tezuka H, Abe Y, Iwata M, Takeuchi H, Ishikawa H et al. 2007. Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature 448:929–33
    [Google Scholar]
  140. 140. 
    Tezuka H, Abe Y, Asano J, Sato T, Liu J et al. 2011. Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction. Immunity 34:247–57
    [Google Scholar]
  141. 141. 
    Kirkland D, Benson A, Mirpuri J, Pifer R, Hou B et al. 2012. B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage. Immunity 36:228–38
    [Google Scholar]
  142. 142. 
    Fukata M, Breglio K, Chen A, Vamadevan AS, Goo T et al. 2008. The myeloid differentiation factor 88 (MyD88) is required for CD4+ T cell effector function in a murine model of inflammatory bowel disease. J. Immunol. 180:1886–94
    [Google Scholar]
  143. 143. 
    Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J 2003. Regulatory T cells selectively express Toll-like receptors and are activated by lipopolysaccharide. J. Exp. Med. 197:403–11
    [Google Scholar]
  144. 144. 
    Liu H, Komai-Koma M, Xu D, Liew FY 2006. Toll-like receptor 2 signaling modulates the functions of CD4+CD25+ regulatory T cells. PNAS 103:7048–53
    [Google Scholar]
  145. 145. 
    Sutmuller RP, den Brok MH, Kramer M, Bennink EJ, Toonen LW et al. 2006. Toll-like receptor 2 controls expansion and function of regulatory T cells. J. Clin. Investig. 116:485–94
    [Google Scholar]
  146. 146. 
    An D, Oh SF, Olszak T, Neves JF, Avci FY et al. 2014. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 156:123–33
    [Google Scholar]
  147. 147. 
    Round JL, Mazmanian SK. 2010. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. PNAS 107:12204–9
    [Google Scholar]
  148. 148. 
    Mazmanian SK, Round JL, Kasper DL 2008. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620–25
    [Google Scholar]
  149. 149. 
    Dasgupta S, Erturk-Hasdemir D, Ochoa-Reparaz J, Reinecker HC, Kasper DL 2014. Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms. Cell Host Microbe 15:413–23
    [Google Scholar]
  150. 150. 
    Sears CL, Geis AL, Housseau F 2014. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J. Clin. Investig. 124:4166–72
    [Google Scholar]
  151. 151. 
    Lee YK, Mehrabian P, Boyajian S, Wu WL, Selicha J et al. 2018. The protective role of Bacteroides fragilis in a murine model of colitis-associated colorectal cancer. mSphere 3:e00587–18
    [Google Scholar]
  152. 152. 
    Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL 2005. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122:107–18
    [Google Scholar]
  153. 153. 
    Wang Q, McLoughlin RM, Cobb BA, Charrel-Dennis M, Zaleski KJ et al. 2006. A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2. J. Exp. Med. 203:2853–63
    [Google Scholar]
  154. 154. 
    Round JL, Lee SM, Li J, Tran G, Jabri B et al. 2011. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332:974–77
    [Google Scholar]
  155. 155. 
    Chu H, Khosravi A, Kusumawardhani IP, Kwon AH, Vasconcelos AC et al. 2016. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science 352:1116–20
    [Google Scholar]
  156. 156. 
    Jeon SG, Kayama H, Ueda Y, Takahashi T, Asahara T et al. 2012. Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon. PLOS Pathog 8:e1002714
    [Google Scholar]
  157. 157. 
    Foligne B, Zoumpopoulou G, Dewulf J, Ben Younes A, Chareyre F et al. 2007. A key role of dendritic cells in probiotic functionality. PLOS ONE 2:e313
    [Google Scholar]
  158. 158. 
    Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E 2017. Dysbiosis and the immune system. Nat. Rev. Immunol. 17:219–32
    [Google Scholar]
  159. 159. 
    Dudakov JA, Hanash AM, van den Brink MR 2015. Interleukin-22: immunobiology and pathology. Annu. Rev. Immunol. 33:747–85
    [Google Scholar]
  160. 160. 
    Zenewicz LA, Yin X, Wang G, Elinav E, Hao L et al. 2013. IL-22 deficiency alters colonic microbiota to be transmissible and colitogenic. J. Immunol. 190:5306–12
    [Google Scholar]
  161. 161. 
    Behnsen J, Jellbauer S, Wong CP, Edwards RA, George MD et al. 2014. The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity 40:262–73
    [Google Scholar]
  162. 162. 
    Kinnebrew MA, Buffie CG, Diehl GE, Zenewicz LA, Leiner I et al. 2012. Interleukin 23 production by intestinal CD103+CD11b+ dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36:276–87
    [Google Scholar]
  163. 163. 
    Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA et al. 2012. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336:1321–25
    [Google Scholar]
  164. 164. 
    Goto Y, Panea C, Nakato G, Cebula A, Lee C et al. 2014. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity 40:594–607
    [Google Scholar]
  165. 165. 
    Lecuyer E, Rakotobe S, Lengline-Garnier H, Lebreton C, Picard M et al. 2014. Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses. Immunity 40:608–20
    [Google Scholar]
  166. 166. 
    Qiu J, Guo X, Chen ZM, He L, Sonnenberg GF et al. 2013. Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity 39:386–99
    [Google Scholar]
  167. 167. 
    Pickard JM, Maurice CF, Kinnebrew MA, Abt MC, Schenten D et al. 2014. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness. Nature 514:638–41
    [Google Scholar]
  168. 168. 
    Goto Y, Lamichhane A, Kamioka M, Sato S, Honda K et al. 2015. IL-10-producing CD4+ T cells negatively regulate fucosylation of epithelial cells in the gut. Sci. Rep. 5:15918
    [Google Scholar]
  169. 169. 
    Dharakul T, Labbe M, Cohen J, Bellamy AR, Street JE et al. 1991. Immunization with baculovirus-expressed recombinant rotavirus proteins VP1, VP4, VP6, and VP7 induces CD8+ T lymphocytes that mediate clearance of chronic rotavirus infection in SCID mice. J. Virol. 65:5928–32
    [Google Scholar]
  170. 170. 
    Lepage AC, Buzoni-Gatel D, Bout DT, Kasper LH 1998. Gut-derived intraepithelial lymphocytes induce long term immunity against Toxoplasma gondii. J. . Immunol 161:4902–8
    [Google Scholar]
  171. 171. 
    Kanwar SS, Ganguly NK, Walia BN, Mahajan RC 1986. Direct and antibody dependent cell mediated cytotoxicity against Giardia lamblia by splenic and intestinal lymphoid cells in mice. Gut 27:73–77
    [Google Scholar]
  172. 172. 
    Chen B, Ni X, Sun R, Zeng B, Wei H et al. 2018. Commensal bacteria-dependent CD8αβ+ T cells in the intestinal epithelium produce antimicrobial peptides. Front. Immunol. 9:1065
    [Google Scholar]
  173. 173. 
    Ismail AS, Behrendt CL, Hooper LV 2009. Reciprocal interactions between commensal bacteria and γδ intraepithelial lymphocytes during mucosal injury. J. Immunol. 182:3047–54
    [Google Scholar]
  174. 174. 
    Ismail AS, Severson KM, Vaishnava S, Behrendt CL, Yu X et al. 2011. γδ intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. PNAS 108:8743–48
    [Google Scholar]
  175. 175. 
    Hoytema van Konijnenburg DP, Reis BS, Pedicord VA, Farache J, Victora GD, Mucida D 2017. Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection. Cell 171:783–94.e13
    [Google Scholar]
  176. 176. 
    Jiang W, Wang X, Zeng B, Liu L, Tardivel A et al. 2013. Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes. J. Exp. Med. 210:2465–76
    [Google Scholar]
  177. 177. 
    Nieuwenhuis EE, Matsumoto T, Lindenbergh D, Willemsen R, Kaser A et al. 2009. Cd1d-dependent regulation of bacterial colonization in the intestine of mice. J. Clin. Investig. 119:1241–50
    [Google Scholar]
  178. 178. 
    Chiba A, Murayama G, Miyake S 2018. Mucosal-associated invariant T cells in autoimmune diseases. Front. Immunol. 9:1333
    [Google Scholar]
  179. 179. 
    Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V et al. 2003. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422:164–69
    [Google Scholar]
  180. 180. 
    Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B et al. 2012. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491:717–23
    [Google Scholar]
  181. 181. 
    Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O et al. 2014. T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature 509:361–65
    [Google Scholar]
  182. 182. 
    Le Bourhis L, Martin E, Peguillet I, Guihot A, Froux N et al. 2010. Antimicrobial activity of mucosal-associated invariant T cells. Nat. Immunol. 11:701–8
    [Google Scholar]
  183. 183. 
    Fagarasan S, Kawamoto S, Kanagawa O, Suzuki K 2010. Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis. Annu. Rev. Immunol. 28:243–73
    [Google Scholar]
  184. 184. 
    Shulzhenko N, Morgun A, Hsiao W, Battle M, Yao M et al. 2011. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat. Med. 17:1585–93
    [Google Scholar]
  185. 185. 
    Suzuki K, Meek B, Doi Y, Muramatsu M, Chiba T et al. 2004. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. PNAS 101:1981–86
    [Google Scholar]
  186. 186. 
    Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T 2002. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science 298:1424–27
    [Google Scholar]
  187. 187. 
    Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, Honjo T 2011. Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nat. Immunol. 12:264–70
    [Google Scholar]
  188. 188. 
    Kawamoto S, Tran TH, Maruya M, Suzuki K, Doi Y et al. 2012. The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science 336:485–89
    [Google Scholar]
  189. 189. 
    Masahata K, Umemoto E, Kayama H, Kotani M, Nakamura S et al. 2014. Generation of colonic IgA-secreting cells in the caecal patch. Nat. Commun. 5:3704
    [Google Scholar]
  190. 190. 
    Wieland A, Frank DN, Harnke B, Bambha K 2015. Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease. Aliment. Pharmacol. Ther. 42:1051–63
    [Google Scholar]
  191. 191. 
    Manichanh C, Borruel N, Casellas F, Guarner F 2012. The gut microbiota in IBD. Nat. Rev. Gastroenterol. Hepatol. 9:599–608
    [Google Scholar]
  192. 192. 
    Noval Rivas M, Crother TR, Arditi M 2016. The microbiome in asthma. Curr. Opin. Pediatr. 28:764–71
    [Google Scholar]
  193. 193. 
    Gerhardt S, Mohajeri MH. 2018. Changes of colonic bacterial composition in Parkinson's disease and other neurodegenerative diseases. Nutrients 10:E708
    [Google Scholar]
  194. 194. 
    Fatkhullina AR, Peshkova IO, Dzutsev A, Aghayev T, McCulloch JA et al. 2018. An interleukin-23-interleukin-22 axis regulates intestinal microbial homeostasis to protect from diet-induced atherosclerosis. Immunity 49:943–57.e9
    [Google Scholar]
  195. 195. 
    Martinez KB, Leone V, Chang EB 2017. Microbial metabolites in health and disease: Navigating the unknown in search of function. J. Biol. Chem. 292:8553–59
    [Google Scholar]
/content/journals/10.1146/annurev-immunol-070119-115104
Loading
/content/journals/10.1146/annurev-immunol-070119-115104
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error