Prevotella copri mediated caffeine metabolism involves ferroptosis of osteoblasts in osteoarthritis

There is positive causality between coffee consumption and osteoarthritis (OA), however, whether gut microbiota is involved in it needs to be discussed. Here, we observed that, in caffeine consumers, fecal Prevotella copri (P. copri) abundance was positively correlated with subchondral bone mass, serum caffeine concentration was negatively correlated with bone mass, and fecal P. copri was negatively correlated with serum caffeine. In OA model, caffeine intake aggravated articular cartilage destruction, bone mass loss and intestinal barrier damage, on the contrary, paraxanthine intake, reversed the above lesions. Importantly, after intestinal P. copri supplement, caffeine induced lesions in OA mice was effectively alleviated. Mechanically, P. copri has the potential to metabolize caffeine into paraxanthine, and this effect could alleviate the ferroptosis of osteoblast in OA model. This study screened out that P. copri, an endogenous bacteria, has the ability to metabolize caffeine and revealed the effects of it on OA progression.