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Here, we demonstrate that dietary chondroitin sulfate (DCS) restores muscle mass and function through a microbiota\u2010dependent gut\u2013muscle metabolic axis. DCS failed to confer protection in germ\u2010free or antibiotic\u2010treated mice, establishing gut microbiota as a prerequisite for its efficacy. Microbiota transplantation and mono\u2010colonization experiments identified\n                    <jats:italic>Lactobacillus johnsonii<\/jats:italic>\n                    Z\u2010RW as a functionally relevant mediator capable of recapitulating muscle protection under controlled microbial conditions. Integrated metagenomic, metabolomic, and proteomic analyses revealed coordinated reprogramming of intestinal sugar utilization and bile acid metabolism following DCS administration. Notably, DCS promoted bile acid deconjugation and enrichment of secondary bile acids, coinciding with restoration of muscle regenerative and energetic programs, including upregulation of NMRK2, PAX7, and SIRT1. Metabolite supplementation further implicated bile acids as candidate mediators linking microbial metabolism to muscle phenotypes. To quantitatively integrate these shifts, we introduce the sugar\u2010bile acid ratio as a systems\u2010level descriptor of microbiota\u2010driven metabolic remodeling. Our findings delineate a microbiota\u2010dependent metabolic framework through which a functional polysaccharide reshapes intestinal biochemistry to influence distal muscle physiology. This work highlights bile acid\u2010associated signaling as a central relay within the gut\u2010muscle axis and provides a conceptual foundation for microbiota\u2010targeted strategies to mitigate muscle wasting.\n                  <\/jats:p>","DOI":"10.1002\/imt2.70118","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:49:19Z","timestamp":1773337759000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chondroitin sulfate restores muscle mass via gut\u2013muscle axis remodeling through sugar\u2013bile acid metabolism reprogramming"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1030-4561","authenticated-orcid":false,"given":"Ruiyun","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Integrated Laboratory of Processing Technology for Chinese Meat and 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