Bacteroides acidifaciens alleviates high-fat diet-induced obesity-related osteoporosis by regulating gut microbiota and bile acid metabolism via the gut-bone axis

Obesity disrupts bone formation-resorption balance. Despite the established role of Bacteroides acidifaciens (B. acidifaciens) in modulating metabolic homeostasis, reducing inflammation, and improving lipid metabolism, its impact on obesity-associated osteoporosis is still not well understood. In this study, we delved into the potential protective influence of B. acidifaciens on high-fat diet (HFD) induced bone loss. The results showed that B. acidifaciens sharply improved weight gain, glucose and lipid metabolism in 16 weeks HFD mice. Both In vitro and in vivo experiments have conclusively demonstrated that the introduction of B. acidifaciens notably ameliorated the imbalance of HFD induced osteogenesis and osteoclastogenesis. B. acidifaciens also regulated HFD induced gut microbiota and bile acid metabolism, and strengthened intestinal mucosal barrier function. Additionally, B. acidifaciens significantly activated the AMPK-PPARα signaling pathway in bone tissue. Thus, our study indicated that B. acidifaciens regulated metabolism, restored gut microbiota balance, and activated AMPK-PPARα pathway to prevent HFD-induced bone loss, potentially aiding in preventing and treating obesity-related osteoporosis.