Coix seed oil alleviates collagen-induced arthritis-associated muscle atrophy and functional decline by modulating gut microbiota dysbiosis

The gut microbiota composition influences the pathogenesis of sarcopenia via the "gut microbiota-muscle axis", with probiotics serving as potential therapeutic agents. Coix seed oil (CSO), a bioactive component of Coix lacryma-jobi l., exhibit potent anti-inflammatory effects, however, its therapeutic role in rheumatoid sarcopenia (RS) and the underlying mechanisms of actions remain incompletely understood. This study investigates the efficacy of CSO in the management of RS and further elucidates its mechanisms of action through the modulation of the "gut microbiota-muscle axis" to alleviate RA-related muscle atrophy. Phytochemicals in CSO were analyzed using UHPLC-OE-MS. A collagen-induced arthritis (CIA) rat model and C2C12 myotube assays were used to evaluate the efficacy of CSO in the alleviation of muscle atrophy. Gut microbiota profiling via 16S rRNA gene sequencing, muscle transcriptomic analysis, and integrative correlation analyses were conducted. Administration of CSO dose-dependently reduced the arthritis index (AI) scores, mitigated muscle loss, and improved grip strength in CIA rats. It also decreased pro-inflammatory cytokines, including serum TNF-α, IL-6, and leptin (all p < 0.05), as well as suppressed the expression of muscle atrophy-related genes. Histologically, CSO improved gastrocnemius pathologies by increasing type I or II fibers, fiber area or density, cross-sectional area (CSA), and satellite cells numbers. Transcriptomic analysis identified 92 downregulated genes and 72 upregulated genes in the CSO group compared to the CIA group. Notably, 16S rRNA sequencing revealed CSO rebalanced gut microbiota, promoting Lactobacillus and Limosilactobacillus while suppressing Bacteroides. Correlation analysis further identified a strong association between these alterations in gut microbiota composition and RS improvements following CSO treatment (p < 0.05). In vitro, CSO reduced leptin-induced atrophy and JAK2-STAT3 activation in C2C12 cells. This study demonstrates that inflammation and gut microbiota contributes to the pathogenesis of CIA-related sarcopenia. Moreover, the gut microbiota-muscle axis and JAK/STAT signaling pathway play key roles in the regulation of muscle atrophy, suggesting that CSO may be a potential therapeutic agent.