Puerarin improves the bone micro-environment to inhibit OVX-induced osteoporosis via modulating SCFAs released by the gut microbiota and repairing intestinal mucosal integrity

Scope: Half of women over the age of 50 will experience a fracture related osteoporosis in their lifetime. The common treatment is estrogen replacement therapy, which can cause many side effects. Puerarin as a phytoestrogen has been proven to improve postmenopausal osteoporosis. However, the mechanisms of anti-osteoporosis remain unclear due to its low bioavailability. The aim of this study is to investigate whether the anti-osteoporosis effects of puerarin are related to modulations in the gut microbiota and focus on the mechanism of gut / bone axis. Methods: We established ovariectomized (OVX) rats as osteoporosis model. The femur was analyzed by micro-computed tomography (mu-CT) and we measured serum biochemical indices and inflammatory factors. 16S rRNA sequencing was employed to evaluate the gut microbiota composition in the fecal samples. Short-chain fatty acids (SCFAs) was analyzed by GC. The expression of intestinal inflammatory factors and adhesion proteins was confirmed by western blotting and qPCR. Results: Puerarin increased the BMD and improved the intestinal mucosal integrity to reduce the systemic inflammation. The disorder of gut microbiota was improved and its metabolites SCFAs were elevated. Metabolic pathways such as amino acid metabolism, LPS biosynthesis and butyrate metabolism were enriched. Conclusion: Puerarin treatment modulated the gut microbiota disorder to elicit the anti-osteoporosis effects in OVX rats, by improving the bone micro-environment via regulating the SCFAs levels and repairing the intestinal mucosal integrity.