Schisandrin B alleviates osteoporosis by regulating gut microbiota homeostasis.

Osteoporosis (OP) is a metabolic bone disease with limited treatment options. Schisandrin B (Sch B) has shown potential in bone regulation, but its mechanisms, particularly regarding the gut-bone axis, remain unclear. An ovariectomized (OVX) mouse model of OP was established and treated with Sch B. Bone microarchitecture was assessed by micro-CT; bone metabolism markers were measured by western blotting; Gut microbiota composition was analyzed via 16 S rRNA sequencing, and fecal short-chain fatty acids (SCFAs) were quantified. Intestinal barrier function was evaluated by histology and tight junction protein expression. In vitro, MC3T3-E1 cells were used to assess osteogenic differentiation and transcriptomic changes. Treatment with Sch B improves bone mineral density and trabecular microarchitecture in OVX mice, promotes bone formation, and inhibits bone resorption. It maintains intestinal integrity, restores mucosal structure, goblet cell function, and the expression of tight junction proteins. Furthermore, it increases microbial a-diversity, restores β-diversity, inhibits the proliferation of pathogenic Proteobacteria and Shigella, and enriches beneficial bacterial groups. Concurrently, it elevates the levels of SCFAs. Critically, ablation of the gut microbiota with antibiotics abolished the osteoprotective effects of Sch B, confirming that its action is dependent on the microbial composition. In vitro, Sch B ameliorates the impairment of osteogenic differentiation and mineralization in MC3T3-E1 cells. Sch B improves bone metabolism and alleviates OP by remodeling the gut microbiota structure and increasing SCFAs, while also enhancing intestinal barrier function to maintain gut microecological homeostasis.