T2DM ‐Induced Gut Dysbiosis Exacerbates Periodontitis Through Intestinal Barrier Disruption and Redox Imbalance

AIM: To investigate the potential role and underlying mechanisms of gut microbiota in type 2 diabetes mellitus (T2DM)-exacerbated periodontitis. MATERIALS AND METHODS: A T2DM-associated periodontitis model was established in C57BL/6 mice and analysed using multi-omics sequencing (16S rRNA, metagenomics and metabolomics). Faecal microbiota transplantation (FMT) from T2DM donors was carried out in recipient mice to investigate the impact of gut dysbiosis on periodontitis. FMT from healthy donors, supplementation of intestinal barrier protectant or the metabolite oleic acid (OA) was administered to mice with T2DM-associated gut dysbiosis to examine their ameliorative effects on periodontal damage. RESULTS: T2DM-associated gut dysbiosis, independent of hyperglycaemia, triggered intestinal barrier disruption, which disturbed systemic redox-related metabolisms and elevated oral oxidative stress, thereby aggravating periodontitis. Restoring gut microbiota via FMT from a healthy donor or protecting the intestinal barrier ameliorated periodontitis. Exogenous supplementary metabolite OA rescued periodontal damage by activating the SIRT1/FoxO1 pathway and enhancing antioxidant enzymes in mice with T2DM-associated gut dysbiosis. CONCLUSIONS: T2DM-induced gut dysbiosis exacerbates periodontitis through intestinal barrier disruption and redox imbalance. These findings provide new adjunctive therapeutic perspectives including microbiota restoration, intestinal barrier protection and antioxidant supplementation for managing patients with T2DM-induced periodontitis.