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Increased gut permeability, microbiota dysbiosis, and aberrant immune microenvironment are the hallmarks of intestinal dysfunctions in aging. Here, we show that subcutaneous WAT dysfunction triggered aging-like intestinal dysfunctions in mouse models. Removal of inguinal subcutaneous WAT (iWAT) increased intestinal permeability and inflammation and altered gut microbiota composition as well as susceptibility to pathogen infection in mouse models. These intestinal dysfunctions were accompanied by a reduction of immunoglobulin A\u2013producing (IgA-producing) cells and IgA biosynthesis in the lamina propria of the small intestine. Retinoic acid (RA) is a key cargo within iWAT-derived extracellular vesicles (iWAT-EVs), which, at least in part, elicits IgA class-switching and production in the small intestine and maintains microbiota homeostasis. RA content in iWAT-EVs and intestinal IgA biosynthesis are reduced during aging in mice. Replenishment of \u201cyoung\u201d iWAT-EVs rejuvenates intestinal IgA production machinery and shifts microbiota composition of aged mice to a \u201cyouth\u201d status, which alleviates leaky gut via RA. In conclusion, our findings suggest that iWAT-EVs with RA orchestrate IgA-mediated gut microbiota homeostasis by acting on intestinal B cells, thereby maintaining intestinal health during aging.<\/jats:p>","DOI":"10.1172\/jci188947","type":"journal-article","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T19:00:52Z","timestamp":1763319652000},"source":"Crossref","is-referenced-by-count":6,"title":["Subcutaneous white adipose tissue\u2013derived extracellular vesicles maintain intestinal homeostasis via IgA biosynthesis in aging mice"],"prefix":"10.1172","volume":"135","author":[{"given":"KeKao","family":"Long","sequence":"first","affiliation":[{"name":"Department of Health Technology and Informatics,"},{"name":"Shenzhen Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pujie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Health Technology and Informatics,"},{"name":"Shenzhen Research Institute, 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