Background: Coix seed (Coix lacryma-jobi L.), a widely consumed medicinal and edible food in Asian countries, has attracted growing interest in functional food research. Among its bioactive constituents, coix seed polysaccharides (CSP) have emerged as promising candidates for managing chronic inflammatory disorders. This study aimed to preliminarily evaluate whether CSP could alleviate rheumatoid arthritis (RA) through modulating gut microbiota and their derived metabolites, moving beyond the conventional focus on short-chain fatty acids (SCFAs). Methods: An experimental RA model was established in rats using complete Freund’s adjuvant (CFA), and the therapeutic potential of CSP was screened through serum inflammatory factor analysis, histopathological evaluation, shotgun metagenomic sequencing-based gut microbiota profiling, and untargeted serum metabolomics. Results: CSP treatment significantly reduced paw swelling and ameliorated synovial injury in CFA-induced rats. Untargeted metabolomics revealed that CSP restored perturbed levels of α-linolenic acid and other host-microbial co-metabolites, while partially reconstituting the disrupted gut microbiota, notably increasing Lactobacillus intestinalis abundance. Correlation analyses linked these alterations to decreased inflammatory factors. KEGG functional prediction suggested a possible involvement of MAPK signaling. Conclusion: These findings suggest that CSP exerts anti-RA effects in association with systematic modulation of gut microbiota and host metabolism, highlighting the potential of dietary polysaccharides from medicinal food sources as broad-spectrum metabolic regulators for managing chronic inflammatory diseases.

BackgroundCoix seed (Coix lacryma-jobi L.), a widely consumed medicinal and edible food in Asian countries, has attracted growing interest in functional food research. Among its bioactive constituents, coix seed polysaccharides (CSP) have emerged as promising candidates for managing chronic inflammatory disorders. This study aimed to preliminarily evaluate whether CSP could alleviate rheumatoid arthritis (RA) through modulating gut microbiota and their derived metabolites, moving beyond the conventional focus on short-chain fatty acids (SCFAs).MethodsAn experimental RA model was established in rats using complete Freund’s adjuvant (CFA), and the therapeutic potential of CSP was screened through serum inflammatory factor analysis, histopathological evaluation, shotgun metagenomic sequencing-based gut microbiota profiling, and untargeted serum metabolomics.ResultsCSP treatment significantly reduced paw swelling and ameliorated synovial injury in CFA-induced rats. Untargeted metabolomics revealed that CSP restored perturbed levels of α-linolenic acid and other host-microbial co-metabolites, while partially reconstituting the disrupted gut microbiota, notably increasing Lactobacillus intestinalis abundance. Correlation analyses linked these alterations to decreased inflammatory factors. KEGG functional prediction suggested a possible involvement of MAPK signaling.ConclusionThese findings suggest that CSP exerts anti-RA effects in association with systematic modulation of gut microbiota and host metabolism, highlighting the potential of dietary polysaccharides from medicinal food sources as broad-spectrum metabolic regulators for managing chronic inflammatory diseases.