Gut Microbiota and IL-17A: Physiological and Pathological Responses


IL-17A is a cytokine which is produced by several immune and non-immune cells. The cytokine plays dual roles from protection from microbes and protection from pro-inflammatory based diseases to induction of the pro-inflammatory based diseases. The main mechanisms which lead to the controversial roles of IL-17A are yet to be clarified. Gut microbiota (GM) are the resident probiotic bacteria in the gastrointestinal tracts which have been introduced as a plausible regulator of IL-17A production and functions. This review article describes the recent information regarding the roles played by GM in determination of IL-17A functions outcome.

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  1. 1.

    Xu M-Q, Cao H-L, Wang W-Q, Wang S, Cao X-C, Yan F, Wang B-M (2015) Fecal microbiota transplantation broadening its application beyond intestinal disorders. World J Gastroenterol: WJG 21(1):102

    CAS  PubMed  Google Scholar 

  2. 2.

    Walker AW, Duncan SH, Louis P, Flint HJ (2014) Phylogeny, culturing, and metagenomics of the human gut microbiota. Trends Microbiol 22(5):267–274

    CAS  PubMed  Google Scholar 

  3. 3.

    Tailford LE, Crost EH, Kavanaugh D, Juge N (2015) Mucin glycan foraging in the human gut microbiome. Front Genet 6:81

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Halfvarson J, Brislawn CJ, Lamendella R, Vázquez-Baeza Y, Walters WA, Bramer LM, D'Amato M, Bonfiglio F, McDonald D, Gonzalez A (2017) Dynamics of the human gut microbiome in inflammatory bowel disease. Nature Microbiology 2:17004

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Xu Z, Knight R (2015) Dietary effects on human gut microbiome diversity. Br J Nutr 113(S1):S1–S5

    CAS  PubMed  Google Scholar 

  6. 6.

    Zackular JP, Baxter NT, Iverson KD, Sadler WD, Petrosino JF, Chen GY, Schloss PD (2013) The gut microbiome modulates colon tumorigenesis. MBio 4(6):e00692–e00613

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Wu H-J, Wu E (2012) The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes 3(1):4–14.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Steves CJ, Bird S, Williams FM, Spector TD (2016) The microbiome and musculoskeletal conditions of aging: a review of evidence for impact and potential therapeutics. J Bone Miner Res 31(2):261–269

    PubMed  Google Scholar 

  9. 9.

    Cerniglia CE, Pineiro SA, Kotarski SF (2016) An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome. Drug Testing and Analysis 8(5–6):539–548

    CAS  PubMed  Google Scholar 

  10. 10.

    Walters WA, Xu Z, Knight R (2014) Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 588(22):4223–4233

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Arndtz K, Hirschfield GM (2016) The pathogenesis of autoimmune liver disease. Dig Dis 34(4):327–333.

    Article  PubMed  Google Scholar 

  12. 12.

    Ramos-Levi AM, Marazuela M (2016) Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms. Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion 63(8):421–429.

    Article  Google Scholar 

  13. 13.

    Arababadi MK, Bidaki MZ, Kennedy D (2014) IL-17A in hepatitis B infection: friend or foe? Arch Virol 159(8):1883–1888

    CAS  PubMed  Google Scholar 

  14. 14.

    Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21 (4):467–476.

  15. 15.

    McKenzie BS, Kastelein RA, Cua DJ (2006) Understanding the IL-23-IL-17 immune pathway. Trends Immunol 27(1):17–23.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Da Silva CA, Hartl D, Liu W, Lee CG, Elias JA (2008) TLR-2 and IL-17A in chitin-induced macrophage activation and acute inflammation. J Immunol 181(6):4279–4286

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Schulz SM, Köhler G, Holscher C, Iwakura Y, Alber G (2008) IL-17A is produced by Th17, γδ T cells and other CD4−lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance. Int Immunol 20(9):1129–1138

    CAS  PubMed  Google Scholar 

  18. 18.

    Vaknin-Dembinsky A, Balashov K, Weiner HL (2006) IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production. J Immunol 176(12):7768–7774

    CAS  PubMed  Google Scholar 

  19. 19.

    Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F (2002) A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168(11):5699–5708

    CAS  PubMed  Google Scholar 

  20. 20.

    Fathalizadeh J, Fathalizadeh H, Mirzabeigi M, Hakimi H, Arababadi MK (2017) The Role of Interleukin-17A (IL-17A) in depression Iran Red Cresc Med J Article in press

  21. 21.

    Marques JM, Rial A, Munoz N, Pellay FX, Van Maele L, Leger H, Camou T, Sirard JC, Benecke A, Chabalgoity JA (2012) Protection against Streptococcus pneumoniae serotype 1 acute infection shows a signature of Th17- and IFN-gamma-mediated immunity. Immunobiology 217(4):420–429

    CAS  PubMed  Google Scholar 

  22. 22.

    Marwaha AK, Leung NJ, McMurchy AN, Levings MK (2012) TH17 Cells in autoimmunity and immunodeficiency: protective or pathogenic? Front Immunol 3:129.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Gaffen S (2016) IL-17 receptor composition. Nat Rev Immunol 16(1):4.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Moseley TA, Haudenschild DR, Rose L, Reddi AH (2003) Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev 14(2):155–174

    CAS  PubMed  Google Scholar 

  25. 25.

    Park JH, Jeong SY, Choi AJ, Kim SJ (2015) Lipopolysaccharide directly stimulates Th17 differentiation in vitro modulating phosphorylation of RelB and NF-kappaB1. Immunol Lett 165(1):10–19.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, Mulder I, Lan A, Bridonneau C, Rochet V, Pisi A, De Paepe M, Brandi G, Eberl G, Snel J, Kelly D, Cerf-Bensussan N (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31(4):677–689.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Luzza F, Parrello T, Monteleone G, Sebkova L, Romano M, Zarrilli R, Imeneo M, Pallone F (2000) Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa. J Immunol 165(9):5332–5337

    CAS  PubMed  Google Scholar 

  28. 28.

    Kamiya T, Watanabe Y, Makino S, Kano H, Tsuji NM (2016) Improvement of intestinal immune cell function by lactic acid bacteria for dairy products. Microorganisms 5(1):1.

    CAS  Article  PubMed Central  Google Scholar 

  29. 29.

    Ren W, Chen S, Zhang L, Liu G, Hussain T, Hao X, Yin J, Duan J, Tan B, Wu G, Bazer FW, Yin Y (2016) Interferon tau affects mouse intestinal microbiota and expression of IL-17. Mediat Inflamm 2016:2839232.

    CAS  Article  Google Scholar 

  30. 30.

    Hergott CB, Roche AM, Tamashiro E, Clarke TB, Bailey AG, Laughlin A, Bushman FD, Weiser JN (2016) Peptidoglycan from the gut microbiota governs the lifespan of circulating phagocytes at homeostasis. Blood 127(20):2460–2471.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Sano T, Huang W, Hall JA, Yang Y, Chen A, Gavzy SJ, Lee JY, Ziel JW, Miraldi ER, Domingos AI, Bonneau R, Littman DR (2015) An IL-23R/IL-22 circuit regulates epithelial serum amyloid a to promote local effector Th17 responses. Cell 163(2):381–393.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Ivanov II, Frutos Rde L, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, Finlay BB, Littman DR (2008) Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4(4):337–349

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139(3):485–498

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Fricke WF, Song Y, Wang AJ, Smith A, Grinchuk V, Mongodin E, Pei C, Ma B, Lu N, Urban JF Jr, Shea-Donohue T, Zhao A (2015) Type 2 immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis. Microbiome 3:40.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Burgess SL, Buonomo E, Carey M, Cowardin C, Naylor C, Noor Z, Wills-Karp M, Petri WA Jr (2014) Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis. MBio 5(6):e01817.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Ivanov, II, Manel N (2010) [Induction of gut mucosal Th17 cells by segmented filamentous bacteria]. Med Sci (Paris) 26 (4):352–355.

  37. 37.

    Atarashi K, Tanoue T, Umesaki Y, Honda K (2010) Regulation of Th17 cell differentiation by intestinal commensal bacteria. Benef Microbes 1(4):327–334

    CAS  PubMed  Google Scholar 

  38. 38.

    Wang S, Charbonnier LM, Noval Rivas M, Georgiev P, Li N, Gerber G, Bry L, Chatila TA (2015) MyD88 adaptor-dependent microbial sensing by regulatory T cells promotes mucosal tolerance and enforces commensalism. Immunity 43(2):289–303

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Shih VF, Cox J, Kljavin NM, Dengler HS, Reichelt M, Kumar P, Rangell L, Kolls JK, Diehl L, Ouyang W, Ghilardi N (2014) Homeostatic IL-23 receptor signaling limits Th17 response through IL-22-mediated containment of commensal microbiota. Proc Natl Acad Sci U S A 111(38):13942–13947.

  40. 40.

    Nishio J, Honda K (2012) Immunoregulation by the gut microbiota. Cell Mol Life Sci 69(21):3635–3650.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Tanabe S (2013) The effect of probiotics and gut microbiota on Th17 cells. Int Rev Immunol 32(5–6):511–525.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Atarashi K, Tanoue T, Honda K (2010) Induction of lamina propria Th17 cells by intestinal commensal bacteria. Vaccine 28(50):8036–8038

    CAS  PubMed  Google Scholar 

  43. 43.

    Van Praet JT, Donovan E, Vanassche I, Drennan MB, Windels F, Dendooven A, Allais L, Cuvelier CA, van de Loo F, Norris PS, Kruglov AA, Nedospasov SA, Rabot S, Tito R, Raes J, Gaboriau-Routhiau V, Cerf-Bensussan N, Van de Wiele T, Eberl G, Ware CF, Elewaut D (2015) Commensal microbiota influence systemic autoimmune responses. EMBO J 34(4):466–474

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Lochner M, Berard M, Sawa S, Hauer S, Gaboriau-Routhiau V, Fernandez TD, Snel J, Bousso P, Cerf-Bensussan N, Eberl G (2011) Restricted microbiota and absence of cognate TCR antigen leads to an unbalanced generation of Th17 cells. J Immunol 186(3):1531–1537

    CAS  PubMed  Google Scholar 

  45. 45.

    Jellbauer S, Perez Lopez A, Behnsen J, Gao N, Nguyen T, Murphy C, Edwards RA, Raffatellu M (2016) Beneficial effects of sodium phenylbutyrate administration during infection with Salmonella enterica Serovar Typhimurium. Infect Immun 84(9):26-39-265.

    CAS  Article  Google Scholar 

  46. 46.

    Kumar P, Monin L, Castillo P, Elsegeiny W, Horne W, Eddens T, Vikram A, Good M, Schoenborn AA, Bibby K, Montelaro RC, Metzger DW, Gulati AS, Kolls JK (2016) Intestinal Interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation. Immunity 44(3):659–671.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Cao AT, Yao S, Gong B, Nurieva RI, Elson CO, Cong Y (2015) Interleukin (IL)-21 promotes intestinal IgA response to microbiota. Mucosal Immunol 8(5):1072–1082.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Rizzo A, Losacco A, Carratelli CR, Domenico MD, Bevilacqua N (2013) Lactobacillus plantarum reduces streptococcus pyogenes virulence by modulating the IL-17, IL-23 and toll-like receptor 2/4 expressions in human epithelial cells. Int Immunopharmacol 17(2):453–461.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Zhang Z, Andoh A, Inatomi O, Bamba S, Takayanagi A, Shimizu N, Fujiyama Y (2005) Interleukin-17 and lipopolysaccharides synergistically induce cyclooxygenase-2 expression in human intestinal myofibroblasts. J Gastroenterol Hepatol 20(4):619–627.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Geem D, Medina-Contreras O, McBride M, Newberry RD, Koni PA, Denning TL (2014) Specific microbiota-induced intestinal Th17 differentiation requires MHC class II but not GALT and mesenteric lymph nodes. J Immunol 193(1):431–438

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Cha HR, Chang SY, Chang JH, Kim JO, Yang JY, Kim CH, Kweon MN (2010) Downregulation of Th17 cells in the small intestine by disruption of gut flora in the absence of retinoic acid. J Immunol 184(12):6799–6806

    CAS  PubMed  Google Scholar 

  52. 52.

    McAleer JP, Nguyen NL, Chen K, Kumar P, Ricks DM, Binnie M, Armentrout RA, Pociask DA, Hein A, Yu A, Vikram A, Bibby K, Umesaki Y, Rivera A, Sheppard D, Ouyang W, Hooper LV, Kolls JK (2016) Pulmonary Th17 antifungal immunity is regulated by the gut microbiome. J Immunol 197(1):97–107

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Hong CP, Park A, Yang BG, Yun CH, Kwak MJ, Lee GW, Kim JH, Jang MS, Lee EJ, Jeun EJ, You G, Kim KS, Choi Y, Park JH, Hwang D, Im SH, Kim JF, Kim YK, Seoh JY, Surh CD, Kim YM, Jang MH (2017) Gut-specific delivery of T-helper 17 cells reduces obesity and insulin resistance in mice. Gastroenterology 152(8):1998–2010.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Varelias A, Ormerod KL, Bunting MD, Koyama M, Gartlan KH, Kuns RD, Lachner N, Locke KR, Lim CY, Henden AS, Zhang P, Clouston AD, Hasnain SZ, McGuckin MA, Blazar BR, MacDonald KPA, Hugenholtz P, Hill GR (2017) Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood 129(15):2172–2185.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Liu X, Zeng B, Zhang J, Li W, Mou F, Wang H, Zou Q, Zhong B, Wu L, Wei H, Fang Y (2016) Role of the gut microbiome in modulating arthritis progression in mice. Sci Rep 6:30594.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Zhang M, Jiang Z, Li D, Jiang D, Wu Y, Ren H, Peng H, Lai Y (2015) Oral antibiotic treatment induces skin microbiota dysbiosis and influences wound healing. Microb Ecol 69(2):415–421.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Stntzing S, Heuschmann P, Barbera L, Ocker M, Jung A, Kirchner T, Neureiter D (2005) Overexpression of MMP9 and tissue factor in unstable carotid plaques associated with Chlamydia pneumoniae, inflammation, and apoptosis. Annal Vascular Surgery 19(3):310–319

    Google Scholar 

  58. 58.

    Kaplan RC, Smith NL, Zucker S, Heckbert SR, Rice K, Psaty BM (2008) Matrix metalloproteinase-3 (MMP3) and MMP9 genes and risk of myocardial infarction, ischemic stroke, and hemorrhagic stroke. Atherosclerosis 201(1):130–137.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Rodrigues DM, Sousa AJ, Hawley SP, Vong L, Gareau MG, Kumar SA, Johnson-Henry KC, Sherman PM (2012) Matrix metalloproteinase 9 contributes to gut microbe homeostasis in a model of infectious colitis. BMC Microbiol 12(1):105.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Wolf KJ, Daft JG, Tanner SM, Hartmann R, Khafipour E, Lorenz RG (2014) Consumption of acidic water alters the gut microbiome and decreases the risk of diabetes in NOD mice. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 62(4):237–250.

    CAS  Article  Google Scholar 

  61. 61.

    Dixon BR, Radin JN, Piazuelo MB, Contreras DC, Algood HM (2016) IL-17a and IL-22 induce expression of antimicrobials in gastrointestinal epithelial cells and may contribute to epithelial cell defense against helicobacter pylori. PLoS One 11(2):e0148514.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Crhanova M, Hradecka H, Faldynova M, Matulova M, Havlickova H, Sisak F, Rychlik I (2011) Immune response of chicken gut to natural colonization by gut microflora and to Salmonella enterica serovar enteritidis infection. Infect Immun 79(7):2755–2763

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, Fujikado N, Tanahashi Y, Akitsu A, Kotaki H, Sudo K, Nakae S, Sasakawa C, Iwakura Y (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30(1):108–119

  64. 64.

    Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203(10):2271–2279

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Mayuzumi H, Inagaki-Ohara K, Uyttenhove C, Okamoto Y, Matsuzaki G (2010) Interleukin-17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa. Immunology 131(3):377–385

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Chandra LC, Traore D, French C, Marlow D, D'Offay J, Clarke SL, Smith BJ, Kuvibidila S (2013) White button, portabella, and shiitake mushroom supplementation up-regulates interleukin-23 secretion in acute dextran sodium sulfate colitis C57BL/6 mice and murine macrophage J.744.1 cell line. Nutr Res 33(5):388–396

    CAS  PubMed  Google Scholar 

  67. 67.

    Malaise Y, Menard S, Cartier C, Lencina C, Sommer C, Gaultier E, Houdeau E, Guzylack-Piriou L (2017) Consequences of bisphenol a perinatal exposure on immune responses and gut barrier function in mice. Arch Toxicol.

  68. 68.

    Raffatellu M, George MD, Akiyama Y, Hornsby MJ, Nuccio SP, Paixao TA, Butler BP, Chu H, Santos RL, Berger T, Mak TW, Tsolis RM, Bevins CL, Solnick JV, Dandekar S, Baumler AJ (2009) Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe 5(5):476–486

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Ziesche E, Bachmann M, Kleinert H, Pfeilschifter J, Muhl H (2007) The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells. J Biol Chem 282(22):16006–16015

    CAS  PubMed  Google Scholar 

  70. 70.

    Huang C, Chen J, Wang J, Zhou H, Lu Y, Lou L, Zheng J, Tian L, Wang X, Cao Z, Zeng Y (2017) Dysbiosis of intestinal microbiota and decreased antimicrobial peptide level in Paneth cells during hypertriglyceridemia-related acute necrotizing pancreatitis in rats. Front Microbiol 8:776.

    Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Lopez P, de Paz B, Rodriguez-Carrio J, Hevia A, Sanchez B, Margolles A, Suarez A (2016) Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep 6:24072.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Fernando MR, Saxena A, Reyes JL, McKay DM (2016) Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages. Am J Physiol-Gastr L 310(10):G822–G831.

    Article  Google Scholar 

  73. 73.

    Heimesaat MM, Grundmann U, Alutis ME, Fischer A, Gobel UB, Bereswill S (2016) The IL-23/IL-22/IL-18 axis in murine Campylobacter jejuni infection. Gut pathogens 8(1):21.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Chen J, Wright K, Davis JM, Jeraldo P, Marietta EV, Murray J, Nelson H, Matteson EL, Taneja V (2016) An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome medicine 8(1):43.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Dorozynska I, Majewska-Szczepanik M, Marcinska K, Szczepanik M (2014) Partial depletion of natural gut flora by antibiotic aggravates collagen induced arthritis (CIA) in mice. Pharmacological reports : PR 66(2):250–255.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Bonnegarde-Bernard A, Jee J, Fial MJ, Aeffner F, Cormet-Boyaka E, Davis IC, Lin M, Tomé D, Karin M, Sun Y (2014) IKKβ in intestinal epithelial cells regulates allergen-specific IgA and allergic inflammation at distant mucosal sites. Mucosal Immunol 7(2):257–267

    CAS  PubMed  Google Scholar 

  77. 77.

    Wang H, Li Y, Feng X, Li Y, Wang W, Qiu C, Xu J, Yang Z, Li Z, Zhou Q, Yao K, Wang H, Li Y, Li D, Dai W, Zheng Y (2016) Dysfunctional gut microbiota and relative co-abundance network in infantile eczema. Gut pathogens 8(1):36.

    Article  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Niess JH, Leithauser F, Adler G, Reimann J (2008) Commensal gut flora drives the expansion of proinflammatory CD4 T cells in the colonic lamina propria under normal and inflammatory conditions. J Immunol 180(1):559–568

    CAS  PubMed  Google Scholar 

  79. 79.

    Kanda T, Nishida A, Ohno M, Imaeda H, Shimada T, Inatomi O, Bamba S, Sugimoto M, Andoh A (2016) Enterococcus durans TN-3 induces regulatory T cells and suppresses the development of dextran sulfate sodium (DSS)-induced experimental colitis. PLoS One 11(7):e0159705.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Liu W, Tan ZL, Xue JF, Luo WJ, Song H, Lv XB, Zheng TJ, Xi T, Xing YY (2016) Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection. Appl Microbiol Biot 100(14):6219–6229.

    CAS  Article  Google Scholar 

  81. 81.

    Moya-Perez A, Neef A, Sanz Y (2015) Bifidobacterium pseudocatenulatum CECT 7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in high-fat diet-fed mice. PLoS One 10(7):e0126976.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Capitan-Canadas F, Ocon B, Aranda CJ, Anzola A, Suarez MD, Zarzuelo A, de Medina FS, Martinez-Augustin O (2016) Fructooligosaccharides exert intestinal anti-inflammatory activity in the CD4+ CD62L+ T cell transfer model of colitis in C57BL/6J mice. Eur J Nutr 55(4):1445–1454.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Garidou L, Pomie C, Klopp P, Waget A, Charpentier J, Aloulou M, Giry A, Serino M, Stenman L, Lahtinen S, Dray C, Iacovoni JS, Courtney M, Collet X, Amar J, Servant F, Lelouvier B, Valet P, Eberl G, Fazilleau N, Douin-Echinard V, Heymes C, Burcelin R (2015) The gut microbiota regulates intestinal CD4 T cells expressing RORgammat and controls metabolic disease. Cell Metab 22(1):100–112.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Vital M, Harkema JR, Rizzo M, Tiedje J, Brandenberger C (2015) Alterations of the murine gut microbiome with age and allergic airway disease. J Immunol Res 2015:892568.

    Article  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Sjoberg V, Sandstrom O, Hedberg M, Hammarstrom S, Hernell O, Hammarstrom ML (2013) Intestinal T-cell responses in celiac disease—impact of celiac disease associated bacteria. PLoS One 8(1):e53414.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  86. 86.

    Stanisavljevic S, Lukic J, Momcilovic M, Miljkovic M, Jevtic B, Kojic M, Golic N, Mostarica Stojkovic M, Miljkovic D (2016) Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis. Benef Microbes 7(3):363–373.

    CAS  Article  PubMed  Google Scholar 

  87. 87.

    Zanvit P, Konkel JE, Jiao X, Kasagi S, Zhang D, Wu R, Chia C, Ajami NJ, Smith DP, Petrosino JF, Abbatiello B, Nakatsukasa H, Chen Q, Belkaid Y, Chen ZJ, Chen W (2015) Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis. Nat Commun 6:8424.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Fricke WF, Song Y, Wang A-J, Smith A, Grinchuk V, Pei C, Ma B, Lu N, Urban JF, Shea-Donohue T (2015) Type 2 immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis. Microbiome 3(1):40

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C, Mathis D (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32(6):815–827

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Lee H, Jin BE, Jang E, Lee AR, Han DS, Kim HY, Youn J (2014) Gut-residing microbes alter the host susceptibility to autoantibody-mediated arthritis. Immune Netw 14(1):38–44.

    Article  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Harley IT, Stankiewicz TE, Giles DA, Softic S, Flick LM, Cappelletti M, Sheridan R, Xanthakos SA, Steinbrecher KA, Sartor RB, Kohli R, Karp CL, Divanovic S (2014) IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice. Hepatology 59(5):1830–1839.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Jin S, Zhao D, Cai C, Song D, Shen J, Xu A, Qiao Y, Ran Z, Zheng Q (2017) Low-dose penicillin exposure in early life decreases Th17 and the susceptibility to DSS colitis in mice through gut microbiota modification. Sci Rep 7:43662

    PubMed  PubMed Central  Google Scholar 

  93. 93.

    Alam C, Bittoun E, Bhagwat D, Valkonen S, Saari A, Jaakkola U, Eerola E, Huovinen P, Hanninen A (2011) Effects of a germ-free environment on gut immune regulation and diabetes progression in non-obese diabetic (NOD) mice. Diabetologia 54(6):1398–1406.

    CAS  Article  PubMed  Google Scholar 

  94. 94.

    Rahman A, Fahlgren A, Sundstedt C, Hammarstrom S, Danielsson A, Hammarstrom ML (2011) Chronic colitis induces expression of beta-defensins in murine intestinal epithelial cells. Clin Exp Immunol 163(1):123–130.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Lee YK, Menezes JS, Umesaki Y, Mazmanian SK (2011) Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 108 Suppl 1(Supplement 1):4615–4622.

    Article  PubMed  Google Scholar 

  96. 96.

    Dimmitt RA, Staley EM, Chuang G, Tanner SM, Soltau TD, Lorenz RG (2010) Role of postnatal acquisition of the intestinal microbiome in the early development of immune function. J Pediatr Gastroenterol Nutr 51(3):262–273.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Fujiwara R, Sasajima N, Takemura N, Ozawa K, Nagasaka Y, Okubo T, Sahasakul Y, Watanabe J, Sonoyama K (2010) 2,4-Dinitrofluorobenzene-induced contact hypersensitivity response in NC/Nga mice fed fructo-oligosaccharide. J Nutr Sci Vitaminol 56(4):260–265

    CAS  PubMed  Google Scholar 

  98. 98.

    Alam C, Valkonen S, Palagani V, Jalava J, Eerola E, Hanninen A (2010) Inflammatory tendencies and overproduction of IL-17 in the colon of young NOD mice are counteracted with diet change. Diabetes 59(9):2237–2246.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  99. 99.

    Lee SY, Jeong JJ, Le TH, Eun SH, Nguyen MD, Park JH, Kim DH (2015) Ocotillol, a majonoside R2 metabolite, ameliorates 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice by restoring the balance of Th17/Treg cells. J Agric Food Chem 63(31):7024–7031.

    CAS  Article  PubMed  Google Scholar 

  100. 100.

    Masui R, Sasaki M, Funaki Y, Ogasawara N, Mizuno M, Iida A, Izawa S, Kondo Y, Ito Y, Tamura Y, Yanamoto K, Noda H, Tanabe A, Okaniwa N, Yamaguchi Y, Iwamoto T, Kasugai K (2013) G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells. Inflamm Bowel Dis 19(13):2848–2856.

    Article  PubMed  Google Scholar 

  101. 101.

    Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, Suda W, Imaoka A, Setoyama H, Nagamori T, Ishikawa E, Shima T, Hara T, Kado S, Jinnohara T, Ohno H, Kondo T, Toyooka K, Watanabe E, Yokoyama S, Tokoro S, Mori H, Noguchi Y, Morita H, Ivanov II, Sugiyama T, Nunez G, Camp JG, Hattori M, Umesaki Y, Honda K (2015) Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163(2):367–380

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Islander U, Andersson A, Lindberg E, Adlerberth I, Wold AE, Rudin A (2010) Superantigenic Staphylococcus aureus stimulates production of interleukin-17 from memory but not naive T cells. Infect Immun 78(1):381–386

    CAS  PubMed  Google Scholar 

  103. 103.

    Kriegel MA, Sefik E, Hill JA, Wu HJ, Benoist C, Mathis D (2011) Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc Natl Acad Sci U S A 108(28):11548–11553

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Li F, Hao X, Chen Y, Bai L, Gao X, Lian Z, Wei H, Sun R, Tian Z (2017) The microbiota maintain homeostasis of liver-resident γδT-17 cells in a lipid antigen/CD1d-dependent manner. Nat Commun 7:13839

    PubMed  Google Scholar 

  105. 105.

    Dahan S, Roth-Walter F, Arnaboldi P, Agarwal S, Mayer L (2007) Epithelia: lymphocyte interactions in the gut. Immunol Rev 215(1):243–253.

    CAS  Article  PubMed  Google Scholar 

  106. 106.

    Beagley KW, Husband AJ (1998) Intraepithelial lymphocytes: origins, distribution, and function. Crit Rev Immunol 18(3):237–254

    CAS  PubMed  Google Scholar 

  107. 107.

    Rehaume LM, Mondot S, de Carcer DA, Velasco J, Benham H, Hasnain SZ, Bowman J, Ruutu M, Hansbro PM, McGuckin MA, Morrison M, Thomas R (2014) ZAP-70 genotype disrupts the relationship between microbiota and host, leading to spondyloarthritis and ileitis in SKG mice. Arthritis Rheumatol 66(10):2780–2792.

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Ashraf Kariminik.

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Douzandeh-Mobarrez, B., Kariminik, A. Gut Microbiota and IL-17A: Physiological and Pathological Responses. Probiotics & Antimicro. Prot. 11, 1–10 (2019).

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  • Gut microbiota
  • IL-17A
  • Pro-inflammatory-based diseases