Gut Microbial Metabolite Butyrate Regulates Treg/Th17 Cell Balance to Alleviate Diabetic Periodontitis

Aim To investigate whether the gut microbiota–derived metabolite butyrate alleviates the progression of diabetic periodontitis by modulating the Treg/Th17 cell balance. Materials and Methods A diabetic periodontitis mouse model was established to assess alveolar bone loss, Treg/Th17 cell subsets, colonic histopathology, faecal microbiota composition and short‐chain fatty acid (SCFA) levels. To investigate microbial causality and therapeutic potential, faecal microbiota transplantation (FMT) and butyrate supplementation were conducted. Results Mice with diabetic periodontitis exhibited a disrupted Treg/Th17 balance accompanied by colonic epithelial damage and a decreased abundance of SCFA‐producing gut microbiota. Faecal SCFA levels showed a downward trend, although the reduction in butyrate was not significant. FMT from diabetic periodontitis mice aggravated periodontal destruction, impaired the colonic mucus barrier and further disturbed Treg/Th17 homeostasis in the recipient mice. These effects were associated with a decrease in SCFA‐producing bacteria and faecal butyrate levels. Moreover, butyrate supplementation significantly alleviated periodontal destruction and restored the Treg/Th17 balance. Conclusion Gut microbiota dysbiosis contributes to diabetic periodontitis progression through disruption of the Treg/Th17 balance, whereas butyrate, as an immunomodulatory SCFA, may alleviate periodontal tissue destruction by restoring this balance.