{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:30:30Z","timestamp":1792384230382,"version":"4.4.0"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T00:00:00Z","timestamp":1565568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008879","name":"California Dairy Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"\n Objective<\/jats:title>\n \n HLA<\/jats:styled-content>\n alleles affect susceptibility to more than 100 diseases, but the mechanisms that account for these genotype\u2013disease associations are largely unknown.\n HLA<\/jats:styled-content>\n alleles strongly influence predisposition to ankylosing spondylitis (\n AS<\/jats:styled-content>\n ) and rheumatoid arthritis (\n RA<\/jats:styled-content>\n ). Both\n AS<\/jats:styled-content>\n and\n RA<\/jats:styled-content>\n patients have discrete intestinal and fecal microbiome signatures. Whether these changes are the cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examined the effect of\n HLA<\/jats:styled-content>\n \u2013B27 and\n HLA<\/jats:styled-content>\n \u2013\n DRB<\/jats:styled-content>\n 1\n RA<\/jats:styled-content>\n risk alleles on the composition of the intestinal microbiome in healthy individuals.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Five hundred sixty\u2010eight stool and biopsy samples from 6 intestinal sites were collected from 107 healthy unrelated subjects, and stool samples were collected from 696 twin pairs from the Twins\n UK<\/jats:styled-content>\n cohort. Microbiome profiling was performed using sequencing of the 16S ribosomal\n RNA<\/jats:styled-content>\n bacterial marker gene. All subjects were genotyped using the Illumina CoreExome\n SNP<\/jats:styled-content>\n microarray, and\n HLA<\/jats:styled-content>\n genotypes were imputed from these data.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Associations were observed between the overall microbial composition and both the\n HLA<\/jats:styled-content>\n \u2013B27 genotype and the\n HLA<\/jats:styled-content>\n \u2013\n DRB<\/jats:styled-content>\n 1\n RA<\/jats:styled-content>\n risk allele (\n P<\/jats:italic>\n = 0.0002 and\n P<\/jats:italic>\n = 0.00001, respectively). These associations were replicated using the stool samples from the Twins\n UK<\/jats:styled-content>\n cohort (\n P<\/jats:italic>\n = 0.023 and\n P<\/jats:italic>\n = 0.033, respectively).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study shows that the changes in intestinal microbiome composition seen in\n AS<\/jats:styled-content>\n and\n RA<\/jats:styled-content>\n are at least partially due to effects of\n HLA<\/jats:styled-content>\n \u2010B27 and\n HLA<\/jats:styled-content>\n \u2013\n DRB<\/jats:styled-content>\n 1 on the gut microbiome. These findings support the hypothesis that\n HLA<\/jats:styled-content>\n alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome and suggest that therapies targeting the microbiome may be effective in preventing or treating these diseases.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.40917","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T22:52:02Z","timestamp":1556664722000},"page":"1642-1650","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["HLA<\/scp>\n Alleles Associated With Risk of Ankylosing Spondylitis and Rheumatoid Arthritis Influence the Gut Microbiome"],"prefix":"10.1002","volume":"71","author":[{"given":"Mark","family":"Asquith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Sternes","sequence":"additional","affiliation":[{"name":"Queensland University of Technology Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary\u2010Ellen","family":"Costello","sequence":"additional","affiliation":[{"name":"Queensland University of Technology Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Karstens","sequence":"additional","affiliation":[{"name":"Oregon Health & Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Diamond","sequence":"additional","affiliation":[{"name":"Oregon Health & Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Oregon Health & Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiu","family":"Li","sequence":"additional","affiliation":[{"name":"Queensland University of Technology Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhairi S.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Queensland University of Technology Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Spector","sequence":"additional","affiliation":[{"name":"King\u2019s College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim\u2010Anh","family":"le Cao","sequence":"additional","affiliation":[{"name":"University of Melbourne Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Oregon Health & Science University and Legacy Devers Eye Institute Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Queensland University of Technology Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780401015"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009740701824613"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200001)43:1<30::AID-ANR5>3.0.CO;2-B"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24385"},{"key":"e_1_2_7_6_1","first-page":"294","article-title":"HLA\u2010B27 related arthritis and bowel inflammation. 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