{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:03:22Z","timestamp":1791475402973,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271828"],"award-info":[{"award-number":["82271828"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013365","name":"West China Hospital","doi-asserted-by":"publisher","award":["ZYGD18015"],"award-info":[{"award-number":["ZYGD18015"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFE0108200"],"award-info":[{"award-number":["2019YFE0108200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>In this study, we aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fecal samples were collected from 38 healthy individuals and 53 high\u2010risk RA individuals with anti\u2013citrullinated protein antibody (ACPA) positivity (Pre\u2010RA), 12 of 53 Pre\u2010RA individuals developed RA within 5\u2009years of follow\u2010up. The differences in intestinal microbial composition between the healthy controls and Pre\u2010RA individuals or among Pre\u2010RA subgroups were identified by 16S ribosomal RNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic\u2010pretreated mice that received GM from the healthy control or Pre\u2010RA groups were then evaluated for intestinal permeability, inflammatory cytokines, and immune cell populations. Collagen\u2010induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from Pre\u2010RA individuals on arthritis severity in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Stool microbial diversity was lower in Pre\u2010RA individuals than in healthy controls. The bacterial community structure and function significantly differed between healthy controls and Pre\u2010RA individuals. Although there were differences to some extent in the bacterial abundance among the Pre\u2010RA subgroups, no robust functional differences were observed. The metabolites in the serum of the Pre\u2010RA group were dramatically different from those in the healthy controls group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the Pre\u2010RA group increased intestinal permeability in FMT mice and zonula occludens\u20101 expression in the small intestine and Caco\u20102 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving Pre\u2010RA feces compared to healthy controls. The changes in intestinal permeability and Th17\u2010cell activation prior to arthritis induction enhanced CIA severity in PreRA\u2010FMT mice compared with HC\u2010FMT mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42616","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T11:59:31Z","timestamp":1684843171000},"page":"1736-1748","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Alteration of Gut Microbiota in Individuals at\n                    <scp>High\u2010Risk<\/scp>\n                    for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance"],"prefix":"10.1002","volume":"75","author":[{"given":"Yubin","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Medicine Jinan University  Guangzhou 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Bozec","sequence":"additional","affiliation":[{"name":"Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg (FAU), Department of Internal Medicine 3\u2010Rheumatology and Immunology Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario M.","family":"Zaiss","sequence":"additional","affiliation":[{"name":"Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg (FAU), Department of Internal Medicine 3\u2010Rheumatology and Immunology Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingying","family":"Qing","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease\u2010related Molecular 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