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

To investigate whether the gut microbiota-derived metabolite butyrate alleviates the progression of diabetic periodontitis by modulating the Treg/Th17 cell balance.

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.

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.

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.