{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:51:20Z","timestamp":1790790680781,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T00:00:00Z","timestamp":1504137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08EY022948"],"award-info":[{"award-number":["K08EY022948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>HLA\u2013B27\u2013associated spondyloarthritides are associated with an altered intestinal microbiota and bowel inflammation. We undertook this study to identify HLA\u2013B27\u2013dependent changes in both host and microbial metabolites in the HLA\u2013B27\/\u03b2<jats:sub>2<\/jats:sub>\u2010microglobulin (\u03b2<jats:sub>2<\/jats:sub>m)\u2013transgenic rat and to determine whether microbiota\u2010derived metabolites could impact disease in this major model of spondyloarthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cecal contents were collected from Fischer 344 33\u20133 HLA\u2013B27\/\u03b2<jats:sub>2<\/jats:sub>m\u2013transgenic rats and wild\u2010type controls at 6 weeks (before disease) and 16 weeks (with active bowel inflammation). Metabolomic profiling was performed by high\u2010throughput gas and liquid chromatography\u2013based mass spectrometry. HLA\u2013B27\/\u03b2<jats:sub>2<\/jats:sub>m\u2013transgenic rats were treated with the microbial metabolites propionate or butyrate in drinking water for 10 weeks, and disease activity was subsequently assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our screen identified 582 metabolites, of which more than half were significantly altered by HLA\u2013B27 expression at 16 weeks. Both microbial and host metabolites were altered, with multiple pathways affected, including those for amino acid, carbohydrate, xenobiotic, and medium\u2010chain fatty acid metabolism. Differences were even observed at 6 weeks, with up\u2010regulation of histidine, tyrosine, spermidine, <jats:italic>N<\/jats:italic>\u2010acetylmuramate, and glycerate in HLA\u2013B27\/\u03b2<jats:sub>2<\/jats:sub>m\u2013transgenic rats. Administration of the short\u2010chain fatty acid propionate significantly attenuated HLA\u2013B27\u2013associated inflammatory disease, although this was not associated with increased FoxP3+ T cell induction or with altered expression of the immunomodulatory cytokines interleukin\u201010 (IL\u201010) or IL\u201033 or of the tight junction protein zonula occludens 1. HLA\u2013B27 expression was also associated with altered host expression of messenger RNA for the microbial metabolite receptors free fatty acid receptor 2 (FFAR2), FFAR3, and niacin receptor 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HLA\u2013B27 expression profoundly impacts the intestinal metabolome, with changes evident in rats even at age 6 weeks. Critically, we demonstrate that a microbial metabolite, propionate, attenuates development of HLA\u2013B27\u2013associated inflammatory disease. These and other microbiota\u2010derived bioactive mediators may provide novel treatment modalities in HLA\u2013B27\u2013associated spondyloarthritides.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40183","type":"journal-article","created":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T15:36:39Z","timestamp":1497627399000},"page":"1984-1995","source":"Crossref","is-referenced-by-count":94,"title":["Intestinal Metabolites Are Profoundly Altered in the Context of HLA\u2013B27 Expression and Functionally Modulate Disease in a Rat Model of Spondyloarthritis"],"prefix":"10.1002","volume":"69","author":[{"given":"Mark","family":"Asquith","sequence":"first","affiliation":[{"name":"Oregon Health and Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Davin","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Stauffer","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Michell","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathleen","family":"Janowitz","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoebe","family":"Lin","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Ensign\u2010Lewis","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Kinchen","sequence":"additional","affiliation":[{"name":"Metabolon, Inc. 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