{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:52:24Z","timestamp":1790913144585,"version":"4.1.0"},"reference-count":105,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Major Projects of China","award":["2025ZD1801002"],"award-info":[{"award-number":["2025ZD1801002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The gut microbiota is a key regulatory hub linking environmental exposure, the mucosal barrier, and joint inflammation, and plays an important role in the pathogenesis and progression of rheumatoid arthritis (RA). Mechanistic studies in this field mainly address two interrelated questions: how RA-associated gut microbiota modulate mucosal immunity and systemic autoimmunity through strain-level variation, niche competition, and metabolic remodeling; and how disease stage, host immune status, and drug exposure reciprocally reshape gut microbial structure and function. Accordingly, this review follows the framework of \u201canti-inflammatory\/pro-inflammatory microbial niches\u2014microbiota-derived metabolites\u2014immune cell homing and migration\u201d to summarize recent advances in the role of gut microbiota and their derivatives in RA onset, progression, and therapeutic response. Focusing on disease-stage-specific remodeling of gut functional ecology, we discuss how short-chain fatty acids, tryptophan-derived indoles, bile acids, succinate, and other microbial effector molecules regulate RA immunopathology through regulatory T cells (Treg), regulatory B cells (Breg), type 17 T helper cells (Th17), and IL-17-producing T follicular helper cells (Tfh17), dendritic cells, fibroblast-like synoviocytes, and osteoclasts. We also highlight intestinal antigen sampling, autoantibody generation, immune cell trafficking, and synovial reactivation as key links in the gut\u2013joint axis. This review aims to shift RA microbiome research from taxonomic profiling toward stage-specific functional ecological analysis, providing a basis for risk stratification, therapeutic response prediction, and microbiota-based adjunctive interventions.<\/jats:p>","DOI":"10.3390\/cells15151398","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T01:43:27Z","timestamp":1785721407000},"page":"1398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gut Microbial Functional Ecology and Microbiota-Derived Metabolites in Rheumatoid Arthritis Autoimmunity"],"prefix":"10.3390","volume":"15","author":[{"given":"Xinqian","family":"Rong","sequence":"first","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8655-5132","authenticated-orcid":false,"given":"Yong","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-9198","authenticated-orcid":false,"given":"Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/art.41752","article-title":"2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1007\/s40265-024-02061-0","article-title":"Prevention of Rheumatoid Arthritis in At-Risk Individuals: Current Status and Future Prospects","volume":"84","author":"Toyoda","year":"2024","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1136\/ard-2024-226362","article-title":"Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: A cross-sectional and longitudinal observational study","volume":"84","author":"Rooney","year":"2024","journal-title":"Ann. 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