Periodontitis aggravates bone loss through gut microbiota alterations in ovariectomized mice.

Epidemiological evidence suggests a bidirectional relationship between periodontitis and osteoporosis, yet the underlying mechanisms remain unclear. In this study, using a mouse model combining ovariectomy-induced osteoporosis and ligature-induced periodontitis, we demonstrated that periodontitis significantly aggravated both alveolar and femoral bone loss, impaired intestinal barrier integrity, and elevated systemic inflammation. Gut microbiota and metabolomic analyses revealed that periodontitis induced distinct alterations in gut microbial composition and intestinal metabolic profiles, potentially contributing to systemic inflammation and bone metabolic dysregulation. Furthermore, fecal microbiota transplantation demonstrated that gut microbiota from periodontitis donors aggravated bone loss and inflammation in recipient mice, whereas microbiota from donors that received periodontal treatment partially alleviated inflammatory responses and skeletal deterioration. Collectively, these findings suggest that periodontitis may aggravate osteoporosis via gut microbiota-mediated mechanisms, highlighting the importance of maintaining oral health to mitigate the adverse impact of periodontitis on systemic bone metabolism.