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Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus\u2010like symptoms. Microbiota reconstitution effectively reduces systemic class switch recombination (CSR) and elevates immunoglobulin heavy chain (IGH) na\u00efve isotype. Microbiota profiling reveals an enrichment of\n                    <jats:italic>Lactobacillus johnsonii<\/jats:italic>\n                    post\u2010FMT, with a significant correlation to purine metabolites. Importantly, the\n                    <jats:italic>L. johnsonii<\/jats:italic>\n                    \u2010derived inosine, an intermediate metabolite in purine metabolism, effectively alleviates lupus pathogenesis in mice. Inosine inhibits B cell differentiation and reduces renal B cell infiltration to protect mice from lupus. At the molecular level, inosine reprograms B cells through the extracellular signal\u2010regulated kinase (ERK)\u2010hypoxia\u2010inducible factor\u20101alpha (HIF\u20101\u03b1) signaling pathway. Therefore, this study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome\u2010based therapeutic approaches.\n                  <\/jats:p>","DOI":"10.1002\/advs.202409837","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:27:01Z","timestamp":1745818021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Microbiota\u2010Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration"],"prefix":"10.1002","volume":"12","author":[{"given":"Lingyu","family":"Gao","sequence":"first","affiliation":[{"name":"Hospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College  Nanjing 210042 China"},{"name":"Key Laboratory of Basic and Translational Research on Immune\u2010Mediated Skin Diseases Chinese Academy 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