Increased serum α-tocopherol acetate mediated by gut microbiota ameliorates alveolar bone loss through the STAT3 signalling pathway in diabetic periodontitis.

ABSTRACT

AIM: To evaluate whether and how gut microbiota-meditated metabolites regulate alveolar bone homeostasis in diabetic periodontitis (DP). MATERIALS AND METHODS: Lactobacillus casei (L. casei) was employed as a positive modulator of gut microbiota in DP mice. The destruction of alveolar bone was evaluated. Untargeted metabolomics was conducted to screen out the pivotal metabolites. A co-housing experiment was conducted to determine the connection between the gut microbiota and alpha-tocopherol acetate (α-TA). α-TA was applied to DP mice to investigate its effect against alveolar bone loss. Human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (HGFs) were extracted for the in vitro experiment. Transcriptomic analysis and immunohistochemistry were performed to detect the major affected signalling pathways. RESULTS: Positive regulation of the gut microbiota significantly attenuated alveolar bone loss and increased the serum α-TA level. The alteration in gut microbiota composition could affect the serum α-T (the hydrolysates of α-TA) level. α-TA could alleviate alveolar bone destruction in DP mice and α-T exert beneficial effects on hPDLCs and HGFs. Mechanistically, the STAT3 signalling pathway was the pivotal pathway involved in the protective role of α-TA. CONCLUSIONS: The gut microbiota-α-TA-STAT3 axis plays an important role in the regulation of diabetic alveolar bone homeostasis.