Abstract
Spondyloarthritis (SpA) is chronic inflammatory disease involving joints and the spine. Bowel inflammation is common in SpA, which may be classified as acute or chronic. Chronic gut inflammation is most common in SpA patients with axial involvement as compared to those presenting with peripheral involvement alone. The pathogenesis of gut inflammation in SpA could be explained by two factors—over-activation of immunological cells and altered gut microbiome. This is exemplified by SpA animal models, namely HLA-B27-expressing transgenic animals and SKG mice models. Immunological mechanisms include homing of activated T cells from gut into synovium, excess pro-inflammatory cytokines secretion by immune cells such as IL-23 and genetic variations in immunological genes. The evidence for role of gut microbiome in SpA is gradually emerging. Recently, metagenomic study of gut microbiome by sequencing of microbial nucleic acids has enabled identification of new microbial taxa and their functions in gut of patients with SpA. In SpA, the gut microbiome could emerge as diagnostic and prognostic marker of disease. Modulation of gut microbiome is slated to have therapeutic potential as well.
Similar content being viewed by others
References
Davis JC, Mease PJ (2008) Insights into the pathology and treatment of spondyloarthritis: from the bench to the clinic. Semin Arthritis Rheum 38:83–100. doi:10.1016/j.semarthrit.2007.10.007
Tse SML, Laxer RM (2012) New advances in juvenile spondyloarthritis. Nat Rev Rheumatol 8:269–279. doi:10.1038/nrrheum.2012.37
Mielants H, De Vos M, Cuvelier C, Veys EM (1996) The role of gut inflammation in the pathogenesis of spondyloarthropathies. Acta Clin Belg 51:340–349
Mielants H, Veys EM, Cuvelier C et al (1995) The evolution of spondyloarthropathies in relation to gut histology. II. Histological aspects. J Rheumatol 22:2273–2278
de Vlam K, Mielants H, Cuvelier C et al (2000) Spondyloarthropathy is underestimated in inflammatory bowel disease: prevalence and HLA association. J Rheumatol 27:2860–2865
De Vos M, Mielants H, Cuvelier C et al (1996) Long-term evolution of gut inflammation in patients with spondyloarthropathy. Gastroenterology 110:1696–1703
Scarpa R, Manguso F, D’Arienzo A et al (2000) Microscopic inflammatory changes in colon of patients with both active psoriasis and psoriatic arthritis without bowel symptoms. J Rheumatol 27:1241–1246
Schatteman L, Mielants H, Veys EM et al (1995) Gut inflammation in psoriatic arthritis: a prospective ileocolonoscopic study. J Rheumatol 22:680–683
Goel R, Danda D, Avinash B et al (2013) Clinico-pathological correlation of non specific inflammation in bowel histology with joint manifestation in a tertiary center in South India. Rheumatol Int 33:2149–2152. doi:10.1007/s00296-011-2332-x
Praet LV, den Bosch FEV, Jacques P et al (2013) Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model. Ann Rheum Dis 72:414–417. doi:10.1136/annrheumdis-2012-202135
Praet LV, Jans L, Carron P et al (2014) Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort. Ann Rheum Dis 73:1186–1189. doi:10.1136/annrheumdis-2013-203854
Picco P, Gattorno M, Marchese N et al (2000) Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol 18:773–778
Mielants H, Veys EM, Cuvelier C et al (1993) Gut inflammation in children with late onset pauciarticular juvenile chronic arthritis and evolution to adult spondyloarthropathy—a prospective study. J Rheumatol 20:1567–1572
Jacques P, Elewaut D (2008) Joint expedition: linking gut inflammation to arthritis. Mucosal Immunol 1:364–371. doi:10.1038/mi.2008.24
Langhorst J, Wieder A, Michalsen A et al (2007) Activated innate immune system in irritable bowel syndrome? Gut 56:1325–1326. doi:10.1136/gut.2007.125005
Lin J-F, Chen J-M, Zuo J-H et al (2014) Meta-analysis: fecal calprotectin for assessment of inflammatory bowel disease activity. Inflamm Bowel Dis 20:1407–1415. doi:10.1097/MIB.0000000000000057
Matzkies FG, Targan SR, Berel D et al (2012) Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study. Arthritis Res Ther 14:R261. doi:10.1186/ar4106
Stoll ML, Punaro M, Patel AS (2011) Fecal calprotectin in children with the enthesitis-related arthritis subtype of juvenile idiopathic arthritis. J Rheumatol 38:2274–2275. doi:10.3899/jrheum.110508
Adams DH, Eksteen B (2006) Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol 6:244–251. doi:10.1038/nri1784
Johansson-Lindbom B, Agace WW (2007) Generation of gut-homing T cells and their localization to the small intestinal mucosa. Immunol Rev 215:226–242. doi:10.1111/j.1600-065X.2006.00482.x
Fantini M-C (2009) Common immunologic mechanisms in inflammatory bowel disease and spondyloarthropathies. World J Gastroenterol 15:2472. doi:10.3748/wjg.15.2472
Hindryckx P, Laukens D, Serry G et al (2011) Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic intestinal mucosal phenotype. Ann Rheum Dis 70:2044–2048. doi:10.1136/ard.2010.149229
Salmi M, Rajala P, Jalkanen S (1997) Homing of mucosal leukocytes to joints. Distinct endothelial ligands in synovium mediate leukocyte-subtype specific adhesion. J Clin Invest 99:2165–2172
May E, Märker-Hermann E, Wittig BM et al (2000) Identical T-cell expansions in the colon mucosa and the synovium of a patient with enterogenic spondyloarthropathy. Gastroenterology 119:1745–1755. doi:10.1053/gast.2000.20173
Nagalingam NA, Kao JY, Young VB (2011) Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis. Inflamm Bowel Dis 17:917–926. doi:10.1002/ibd.21462
Dorofeyev AE, Vasilenko IV, Rassokhina OA et al (2013) Mucosal barrier in ulcerative colitis and Crohn’s disease. Gastroenterol Res Pract. doi:10.1155/2013/431231
Heazlewood CK, Cook MC, Eri R et al (2008) Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med 5:e54. doi:10.1371/journal.pmed.0050054
Ciccia F, Accardo-Palumbo A, Rizzo A et al (2014) Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation. Ann Rheum Dis 73:1566–1574. doi:10.1136/annrheumdis-2012-202925
Ciccia F, Bombardieri M, Principato A et al (2009) Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitis. Arthritis Rheum 60:955–965. doi:10.1002/art.24389
Gheita TA, El Gazzar II, El-Fishawy HS et al (2014) Involvement of IL-23 in enteropathic arthritis patients with inflammatory bowel disease: preliminary results. Clin Rheumatol 33:713–717. doi:10.1007/s10067-013-2469-y
Sherlock JP, Joyce-Shaikh B, Turner SP et al (2012) IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+ CD4−CD8− entheseal resident T cells. Nat Med 18:1069–1076. doi:10.1038/nm.2817
Sutton CE, Lalor SJ, Sweeney CM et al (2009) Interleukin-1 and IL-23 induce innate IL-17 production from γδ T cells, amplifying Th17 responses and autoimmunity. Immunity 31:331–341. doi:10.1016/j.immuni.2009.08.001
Costello M-E, Ciccia F, Willner D et al (2014) Intestinal dysbiosis in ankylosing spondylitis. Arthritis Rheumatol. doi:10.1002/art.38967
Poggi A, Zocchi MR (2014) NK cell autoreactivity and autoimmune diseases. Front Immunol 4(5):27. doi:10.3389/fimmu.2014.00027
Walker JA, Barlow JL, McKenzie ANJ (2013) Innate lymphoid cells—how did we miss them? Nat Rev Immunol 13:75–87. doi:10.1038/nri3349
Ciccia F, Accardo-Palumbo A, Giardina A et al (2010) Expansion of intestinal CD4+ CD25high Treg cells in patients with ankylosing spondylitis: a putative role for interleukin-10 in preventing intestinal Th17 response. Arthritis Rheum 62:3625–3634. doi:10.1002/art.27699
Ciccia F, Accardo-Palumbo A, Alessandro R et al (2012) Interleukin-22 and interleukin-22-producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis. Arthritis Rheum 64:1869–1878. doi:10.1002/art.34355
Takayama T, Kamada N, Chinen H et al (2010) Imbalance of NKp44(+)NKp46(−) and NKp44(−)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn’s disease. Gastroenterology 139:882–892. doi:10.1053/j.gastro.2010.05.040
Qiu J, Guo X, Chen ZE et al (2013) Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity 39:386–399. doi:10.1016/j.immuni.2013.08.002
Jr WO, Zenewicz LA, Flavell RA (2010) The dual nature of TH17 cells: shifting the focus to function. Nat Immunol 11:471–476. doi:10.1038/ni.1882
Leung J, Davenport M, Wolff M et al (2014) IL-22-producing CD4+ cells are depleted in actively inflamed colitis tissue. Mucosal Immunol. doi:10.1038/mi.2013.31
Sovran B, Loonen LMP, Lu P et al (2015) IL-22-STAT3 pathway plays a key role in the maintenance of ileal homeostasis in mice lacking secreted mucus barrier. Inflamm Bowel Dis. doi:10.1097/MIB.0000000000000319
Brand S (2009) Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease. Gut 58:1152–1167. doi:10.1136/gut.2008.163667
Ciccia F, Guggino G, Rizzo A et al (2015) Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis. Ann Rheum Dis. doi:10.1136/annrheumdis-2014-206323
Cua DJ, Sherlock JP (2011) Autoimmunity’s collateral damage: gut microbiota strikes “back”. Nat Med 17:1055–1056. doi:10.1038/nm0911-1055
Drummond RA, Saijo S, Iwakura Y, Brown GD (2011) The role of Syk/CARD9 coupled C-type lectins in antifungal immunity. Eur J Immunol 41:276–281. doi:10.1002/eji.201041252
Yoshitomi H, Sakaguchi N, Kobayashi K et al (2005) A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice. J Exp Med 201:949–960. doi:10.1084/jem.20041758
Ruutu M, Thomas G, Steck R et al (2012) β-glucan triggers spondylarthritis and Crohn’s disease-like ileitis in SKG mice. Arthritis Rheum 64:2211–2222. doi:10.1002/art.34423
Poeck H, Bscheider M, Gross O et al (2010) Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat Immunol 11:63–69. doi:10.1038/ni.1824
Sokol H, Conway KL, Zhang M et al (2013) Card9 mediates intestinal epithelial cell restitution, T-helper 17 responses, and control of bacterial infection in mice. Gastroenterology 145(591–601):e3. doi:10.1053/j.gastro.2013.05.047
Ley RE, Peterson DA, Gordon JI (2006) Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124:837–848. doi:10.1016/j.cell.2006.02.017
Qin J, Li R, Raes J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65. doi:10.1038/nature08821
O’Hara AM, Shanahan F (2006) The gut flora as a forgotten organ. EMBO Rep 7:688–693. doi:10.1038/sj.embor.7400731
Rastall RA (2004) Bacteria in the gut: friends and foes and how to alter the balance. J Nutr 134:2022S–2026S
Kostic AD, Howitt MR, Garrett WS (2013) Exploring host–microbiota interactions in animal models and humans. Genes Dev 27:701–718. doi:10.1101/gad.212522.112
Guarner F, Malagelada J-R (2003) Gut flora in health and disease. The Lancet 361:512–519. doi:10.1016/S0140-6736(03)12489-0
Hammer RE, Maika SD, Richardson JA et al (1990) Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: an animal model of HLA-B27-associated human disorders. Cell 63:1099–1112. doi:10.1016/0092-8674(90)90512-D
Taurog JD, Richardson JA, Croft JT et al (1994) The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 180:2359–2364
Rath HC, Herfarth HH, Ikeda JS et al (1996) Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats. J Clin Invest 98:945–953. doi:10.1172/JCI118878
McBurney W, Mangold M, Munro K et al (2006) PCR/DGGE and 16S rRNA gene library analysis of the colonic microbiota of HLA-B27/beta2-microglobulin transgenic rats. Lett Appl Microbiol 42:165–171. doi:10.1111/j.1472-765X.2005.01811.x
Onderdonk AB, Richardson JA, Hammer RE, Taurog JD (1998) Correlation of cecal microflora of HLA-B27 transgenic rats with inflammatory bowel disease. Infect Immun 66:6022–6023
Hacquard-Bouder C, Ittah M, Breban M (2006) Animal models of HLA-B27-associated diseases: new outcomes. Jt Bone Spine Rev Rhum 73:132–138. doi:10.1016/j.jbspin.2005.03.016
Lin P, Bach M, Asquith M et al (2014) HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats. PLoS One 9(8):105684. doi:10.1371/journal.pone.0105684
Rath HC (2002) Role of commensal bacteria in chronic experimental colitis: lessons from the HLA-B27 transgenic rat. Pathobiol J Immunopathol Mol Cell Biol 70:131–138
Png CW, Lindén SK, Gilshenan KS et al (2010) Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol 105:2420–2428. doi:10.1038/ajg.2010.281
Reháková Z, Capková J, Stĕpánková R et al (2000) Germ-free mice do not develop ankylosing enthesopathy, a spontaneous joint disease. Hum Immunol 61:555–558
Sinkorová Z, Capková J, Niederlová J et al (2008) Commensal intestinal bacterial strains trigger ankylosing enthesopathy of the ankle in inbred B10.BR (H-2(k)) male mice. Hum Immunol 69:845–850. doi:10.1016/j.humimm.2008.08.296
Rosenbaum JT, Davey MP (2011) Time for a gut check: evidence for the hypothesis that HLA–B27 predisposes to ankylosing spondylitis by altering the microbiome. Arthritis Rheum 63:3195–3198. doi:10.1002/art.30558
Firestein GS (2004) The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis. J Clin Invest 114:471–474. doi:10.1172/JCI22651
Sakaguchi S, Takahashi T, Hata H et al (2006) SKG mice, a monogenic model of autoimmune arthritis due to altered signal transduction in T-cells. In: Holmdahl R (ed) Hered. Basis Rheum. Dis. Birkhäuser Basel, pp 147–159
Sakaguchi N, Takahashi T, Hata H et al (2003) Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426:454–460. doi:10.1038/nature02119
Benham H, Rehaume LM, Hasnain SZ et al (2014) Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis Rheumatol Hoboken NJ 66:1755–1767. doi:10.1002/art.38638
Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E (2007) Effects of beta-glucans on the immune system. Med Kaunas Lith 43:597–606
Rehaume LM, Mondot S, Aguirre de Cárcer D et al (2014) ZAP-70 genotype disrupts the relationship between microbiota and host, leading to spondyloarthritis and ileitis in SKG mice. Arthritis Rheumatol Hoboken NJ 66:2780–2792. doi:10.1002/art.38773
Ganner A, Schatzmayr G (2012) Capability of yeast derivatives to adhere enteropathogenic bacteria and to modulate cells of the innate immune system. Appl Microbiol Biotechnol 95:289–297. doi:10.1007/s00253-012-4140-y
Stebbings S, Munro K, Simon MA et al (2002) Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis. Rheumatol Oxf Engl 41:1395–1401
Rashid T, Wilson C, Ebringer A (2013) The link between ankylosing spondylitis, Crohn’s disease, Klebsiella, and starch consumption. Clin Dev Immunol. doi:10.1155/2013/872632
Ebringer A, Wilson C (1996) The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis. Clin Rheumatol 15(Suppl 1):62–66
Rashid T, Ebringer A (2011) Gut-mediated and HLA-B27-associated arthritis: an emphasis on ankylosing spondylitis and Crohn’s disease with a proposal for the use of new treatment. Discov Med 12:187–194
Stone MA, Payne U, Schentag C et al (2004) Comparative immune responses to candidate arthritogenic bacteria do not confirm a dominant role for Klebsiella pneumonia in the pathogenesis of familial ankylosing spondylitis. Rheumatol Oxf Engl 43:148–155. doi:10.1093/rheumatology/keg482
Aydin SZ, Atagunduz P, Temel M et al (2008) Anti-Saccharomyces cerevisiae antibodies (ASCA) in spondyloarthropathies: a reassessment. Rheumatology 47:142–144. doi:10.1093/rheumatology/kem324
Wallis D, Asaduzzaman A, Weisman M et al (2013) Elevated serum anti-flagellin antibodies implicate subclinical bowel inflammation in ankylosing spondylitis: an observational study. Arthritis Res Ther 15:R166. doi:10.1186/ar4350
Mundwiler ML, Mei L, Landers CJ et al (2009) Inflammatory bowel disease serologies in ankylosing spondylitis patients: a pilot study. Arthritis Res Ther 11:R177. doi:10.1186/ar2866
Kabeerdoss J, Jayakanthan P, Pugazhendhi S, Ramakrishna BS (2015) Alterations of mucosal microbiota in the colon of patients with inflammatory bowel disease revealed by real time polymerase chain reaction amplification of 16S ribosomal ribonucleic acid. Indian J Med Res 142:23–32. doi:10.4103/0971-5916.162091
Scher JU, Ubeda C, Artacho A et al (2015) Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol Hoboken NJ 67:128–139. doi:10.1002/art.38892
Colmegna I, Cuchacovich R, Espinoza LR (2004) HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations. Clin Microbiol Rev 17:348–369. doi:10.1128/CMR.17.2.348-369.2004
Siala M, Jaulhac B, Gdoura R et al (2008) Analysis of bacterial DNA in synovial tissue of Tunisian patients with reactive and undifferentiated arthritis by broad-range PCR, cloning and sequencing. Arthritis Res Ther 10:R40. doi:10.1186/ar2398
Siala M, Gdoura R, Fourati H et al (2009) Broad-range PCR, cloning and sequencing of the full 16S rRNA gene for detection of bacterial DNA in synovial fluid samples of Tunisian patients with reactive and undifferentiated arthritis. Arthritis Res Ther 11:R102. doi:10.1186/ar2748
Dorofeyev AE, Vasilenko IV, Rassokhina OA (2009) Joint extraintestinal manifestations in ulcerative colitis. Dig Dis Basel Switz 27:502–510. doi:10.1159/000233289
(2014) Poster Sessions. FEBS J 281:65–784. doi:10.1111/febs.12919
Malin M, Verronen P, Mykkänen H et al (1996) Increased bacterial urease activity in faeces in juvenile chronic arthritis: evidence of altered intestinal microflora? Rheumatology 35:689–694. doi:10.1093/rheumatology/35.7.689
Stoll ML, Kumar R, Morrow CD et al (2014) Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis Res Ther 16:486. doi:10.1186/s13075-014-0486-0
Baharav E, Mor F, Halpern M, Weinberger A (2004) Lactobacillus GG bacteria ameliorate arthritis in lewis rats. J Nutr 134:1964–1969
Noto Llana M, Sarnacki SH, Castañeda MDRA et al (2013) Consumption of Lactobacillus casei fermented milk prevents Salmonella reactive arthritis by modulating IL-23/IL-17 expression. PLoS One 8:e82588. doi:10.1371/journal.pone.0082588
Magrone T, Jirillo E (2014) The interleukin-17/interleukin-22 innate axis in the gut as a new drug target in allergic-inflammatory and autoimmune diseases. A working hypothesis. Endocr Metab Immune Disord Drug Targets 14:145–151
Schultz M, Munro K, Tannock GW et al (2004) Effects of feeding a probiotic preparation (SIM) containing inulin on the severity of colitis and on the composition of the intestinal microflora in HLA-B27 transgenic rats. Clin Diagn Lab Immunol 11:581–587. doi:10.1128/CDLI.11.3.581-587.2004
Dieleman LA, Goerres MS, Arends A et al (2003) Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment. Gut 52:370–376
Jenks K, Stebbings S, Burton J et al (2010) Probiotic therapy for the treatment of spondyloarthritis: a randomized controlled trial. J Rheumatol 37:2118–2125. doi:10.3899/jrheum.100193
Brophy S, Burrows CL, Brooks C et al (2008) Internet-based randomised controlled trials for the evaluation of complementary and alternative medicines: probiotics in spondyloarthropathy. BMC Musculoskelet Disord 9:4. doi:10.1186/1471-2474-9-4
Sanges M, Valente G, Rea M et al (2009) Probiotics in spondyloarthropathy associated with ulcerative colitis: a pilot study. Eur Rev Med Pharmacol Sci 13:233–234
Pineiro M, Asp N-G, Reid G et al (2008) FAO technical meeting on prebiotics. J Clin Gastroenterol 42:S156–S159. doi:10.1097/MCG.0b013e31817f184e
Kleessen B, Hartmann L, Blaut M (2001) Oligofructose and long-chain inulin: influence on the gut microbial ecology of rats associated with a human faecal flora. Br J Nutr 86:291–300
Kim CH, Park J, Kim M (2014) Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw 14:277–288. doi:10.4110/in.2014.14.6.277
Casellas F, Borruel N, Torrejón A et al (2007) Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin. Aliment Pharmacol Ther 25:1061–1067. doi:10.1111/j.1365-2036.2007.03288.x
Kanauchi O, Suga T, Tochihara M et al (2013) Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial. J Gastroenterol 37:67–72. doi:10.1007/BF03326417
Scaldaferri F, Gerardi V, Lopetuso LR et al (2013) Gut microbial flora, prebiotics, and probiotics in IBD: their current usage and utility. BioMed Res Int 2013:e435268. doi:10.1155/2013/435268
Hoentjen F, Welling GW, Harmsen HJM et al (2005) Reduction of colitis by prebiotics in HLA-B27 transgenic rats is associated with microflora changes and immunomodulation. Inflamm Bowel Dis 11:977–985
Koleva P, Ketabi A, Valcheva R et al (2014) Chemically defined diet alters the protective properties of fructo-oligosaccharides and isomalto-oligosaccharides in HLA-B27 transgenic rats. PLoS One 9:e111717. doi:10.1371/journal.pone.0111717
Barber CE, Kim J, Inman RD et al (2013) Antibiotics for treatment of reactive arthritis: a systematic review and metaanalysis. J Rheumatol 40:916–928. doi:10.3899/jrheum.121192
Carter JD, Espinoza LR, Inman RD et al (2010) Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial. Arthritis Rheum 62:1298–1307. doi:10.1002/art.27394
Frydén A, Bengtsson A, Foberg U et al (1990) Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study. BMJ 301:1299–1302
Rohekar S, Chan J, Tse SML et al (2015) 2014 Update of the Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada Treatment Recommendations for the management of spondyloarthritis. Part II: specific management recommendations. J Rheumatol 42:654–664. doi:10.3899/jrheum.141001
Bakken JS, Borody T, Brandt LJ et al (2011) Treating clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol 9:1044–1049. doi:10.1016/j.cgh.2011.08.014
Eiseman B, Silen W, Bascom GS, Kauvar AJ (1958) Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 44:854–859
van Nood E, Vrieze A, Nieuwdorp M et al (2013) Duodenal infusion of donor feces for recurrent clostridium difficile. N Engl J Med 368:407–415. doi:10.1056/NEJMoa1205037
Smith MB, Kelly C, Alm EJ (2014) Policy: how to regulate faecal transplants. Nature 506:290–291
Colman RJ, Rubin DT (2014) Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis 8:1569–1581. doi:10.1016/j.crohns.2014.08.006
Anderson CA, Boucher G, Lees CW et al (2011) Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43:246–252. doi:10.1038/ng.764
McGovern DPB, Gardet A, Törkvist L et al (2010) Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet 42:332–337. doi:10.1038/ng.549
Uk, IBD Genetics Consortium, Barrett JC, Lee JC et al (2009) Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nat Genet 41:1330–1334. doi:10.1038/ng.483
Julià A, Domènech E, Ricart E et al (2013) A genome-wide association study on a southern European population identifies a new Crohn’s disease susceptibility locus at RBX1-EP300. Gut 62:1440–1445. doi:10.1136/gutjnl-2012-302865
Franke A, McGovern DPB, Barrett JC et al (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 42:1118–1125. doi:10.1038/ng.717
Evans DM, Spencer CCA, Pointon JJ et al (2011) Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet 43:761–767. doi:10.1038/ng.873
Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678. doi:10.1038/nature05911
Australo-Anglo-American Spondyloarthritis Consortium (TASC), Reveille JD, Sims A-M et al (2010) Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet 42:123–127. doi:10.1038/ng.513
Barrett JC, Hansoul S, Nicolae DL et al (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40:955–962. doi:10.1038/ng.175
Kugathasan S, Baldassano RN, Bradfield JP et al (2008) Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease. Nat Genet 40:1211–1215. doi:10.1038/ng.203
Jostins L, Ripke S, Weersma RK et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124. doi:10.1038/nature11582
Parkes M, Barrett JC, Prescott NJ et al (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 39:830–832. doi:10.1038/ng2061
Libioulle C, Louis E, Hansoul S et al (2007) Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet 3:e58. doi:10.1371/journal.pgen.0030058
Hüffmeier U, Uebe S, Ekici AB et al (2010) Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet 42:996–999. doi:10.1038/ng.688
Haritunians T, Taylor KD, Targan SR et al (2010) Genetic predictors of medically refractory ulcerative colitis. Inflamm Bowel Dis 16:1830–1840. doi:10.1002/ibd.21293
Silverberg MS, Cho JH, Rioux JD et al (2009) Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nat Genet 41:216–220. doi:10.1038/ng.275
Yang S-K, Hong M, Zhao W et al (2014) Genome-wide association study of Crohn’s disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations. Gut 63:80–87. doi:10.1136/gutjnl-2013-305193
Yamazaki K, Umeno J, Takahashi A et al (2013) A genome-wide association study identifies 2 susceptibility loci for Crohn’s disease in a Japanese population. Gastroenterology 144:781–788. doi:10.1053/j.gastro.2012.12.021
Kenny EE, Pe’er I, Karban A et al (2012) A genome-wide scan of Ashkenazi Jewish Crohn’s disease suggests novel susceptibility loci. PLoS Genet 8:e1002559. doi:10.1371/journal.pgen.1002559
Okada Y, Yamazaki K, Umeno J et al (2011) HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases risk for ulcerative colitis but reduces risk for Crohn’s disease. Gastroenterology 141:864–871. doi:10.1053/j.gastro.2011.05.048
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kabeerdoss, J., Sandhya, P. & Danda, D. Gut inflammation and microbiome in spondyloarthritis. Rheumatol Int 36, 457–468 (2016). https://doi.org/10.1007/s00296-015-3414-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-015-3414-y