Fecal microbiota and metabolite profiles in patients with osteoarthritis: a cross-sectional study

Introduction Globally, Osteoarthritis (OA) represents a primary chronic joint condition, rooted in complex mechanisms such as metabolic irregularities, synovitis, immune system responses, and body-wide inflammation. Emerging evidence highlights gut microbiota as a critical mediator of joint inflammation. Methods In this study, 55 OA patients from the affiliated hospital of Anhui Medical University were compared with 55 healthy controls. Using 16S rRNA (V4–V5) sequencing and POS/NEG dualionmode untargeted fecal metabolomics, we investigated the "gutmetabolismimmunityjoint" axis in OA. Results The results indicate that patients with OA exhibit significant gut microbiota dysbiosis, characterised in particular by a reduction in beneficial bacterial groups such as Clostridiales , Lactobacillales , Bacilli and Actinobacteria, and an increase in Bacteroidaceae and Burkholderiales . Metabolomic analysis revealed that metabolic pathways such as beta-alanine metabolism and pyrimidine metabolism were enriched. Specific microbial changes are associated with alterations in host metabolism, for example, a reduction in the beneficial bacteria Actinobacteria was positively correlated with the downregulation of indole-3-acetic acid, which has a beneficial effect; Bacilli and Lactobacillales were associated with the dual loss of luteolin and D-tryptophan. Discussion This study revealed significant alterations in gut microbiota and fecal metabolites in OA patients compared to healthy individuals. The identified differential metabolites hold promise as potential biomarkers for early diagnosis or therapeutic targets, offering new insights for future personalized interventions.