Parabacteroides distasonis ameliorates ovariectomy-induced bone loss by regulating the gut microbiota and Th17/Treg balance.

Postmenopausal osteoporosis is linked to estrogen deficiency, immune imbalance, and gut microbiota alterations that can promote bone loss. Using an ovariectomized (OVX) rat model, we found that Parabacteroides distasonis abundance decreased after OVX. Oral supplementation with live P. distasonis improved distal femoral trabecular microarchitecture and increased femoral bending strength, alongside shifts in bone turnover markers consistent with reduced resorption. Treatment was associated with improved colonic histology, higher expression of tight junction markers (ZO-1 and occludin), and lower circulating LPS. In mesenteric lymph nodes, P. distasonis shifted Th17/Treg-related readouts and cytokine profiles toward a less inflammatory state, with parallel changes in marrow-region markers. 16S rRNA profiling and targeted SCFA analysis showed microbiota remodeling and increased butyrate after treatment. These results support microbiota-based approaches targeting the gut-immune-bone axis to mitigate estrogen deficiency-associated bone loss.