Non‐Surgical Periodontal Therapy and Metformin Improve Bone Loss in Obese Mice With Periodontitis by Modulating the Gut Microbiota

Periodontitis and obesity are chronic inflammatory diseases associated with osteoporosis. Controlling inflammation is crucial for managing periodontitis in individuals with obesity. Metformin has shown potent anti-inflammatory effects under inflammatory conditions. However, the effects of adjunctive systemic administration of metformin alongside non-surgical periodontal therapy (NSPT) on periodontal and systemic bone health in obesity remain unknown. In this study, a high-fat diet (HFD)-induced obese murine model was created with periodontitis through ligation. Periodontal treatment consisted of standard mechanical debridement via NSPT, with or without metformin treatment through oral gavage. Outcomes were evaluated based on changes in periodontal status, systemic bone resorption and inflammation, as well as the gut microbiota community and metabolism. Our results indicated that periodontitis significantly increased osteoclastic activity and resulted in alveolar and femoral bone loss in HFD-fed mice. Compared to NSPT alone, NSPT and metformin significantly improved periodontitis, reduced systemic inflammation, and alleviated femoral bone absorption in HFD-fed mice. Mechanistically, periodontitis promoted gut microbiota dysbiosis and disrupted microbial linoleic acid metabolism. NSPT and metformin normalized the gut microbiota, enhanced the growth of species with anti-inflammatory properties, including Faecalibacterium prausnitzii, Akkermansia muciniphila, Lactobacillus reuteri, and Butyricicoccus pullicaecorum, and restored the balance of linoleic acid metabolism in the gut and serum. This research presents novel evidence that metformin may serve as a promising adjunct to enhance the response of obese subjects to NSPT by regulating the gut microbiota and linoleic acid metabolism, indicating that the gut microbiota could be a potential therapeutic target for multidisciplinary intervention in periodontitis and obesity.