Extracts of Drynariae Rhizoma Promote Bone Formation in OVX Rats through Modulating the Gut Microbiota

Drynariae Rhizoma has been commonly used as a preventive and therapeutic agent for bone diseases. However, its pharmacological mechanisms have not been fully elucidated. Here, we aimed to investigate the effects of Drynariae Rhizoma in a bilateral ovariectomized rat model and explore the correlation with gut microbiome. We established an ovariectomized rat model, which we treated with different doses of Drynariae Rhizoma (Drynariae Rhizoma-Low, 0.27 g/kg/day; Drynariae Rhizoma-Middle, 0.81 g/kg/day; Drynariae Rhizoma-High, 2.43 g/kg/day) through intragastric administration for 12 weeks. Results showed that Drynariae Rhizoma alleviated body weight, moderated bone microstructure, and promoted the expression of bone formation-related factors in ovariectomized rats, in which Drynariae Rhizoma-High showed the most significant effects among the three doses. Furthermore, the effects of Drynariae Rhizoma on promoting bone formation were correlated to the changes in microbial richness and the restorations of several genera, among which <i>Ruminiclostridium</i> and <i>Ruminococcaceae_UCG_007</i> were positively correlated with the bone formation-related factors, and both were enriched in the Drynariae Rhizoma-High group as biomarkers. Moreover, CMP-legionaminate biosynthesis I might be a crucial pathway of Drynariae Rhizoma to regulate gut microbiota. The content of serum short-chain fatty acids in the ovariectomized rats were regulated by Drynariae Rhizoma. Our results demonstrate that Drynariae Rhizoma promotes bone formation in ovariectomized rats, and is related to the regulation of the gut microbiota structure.