Engineered Probiotic Improves Diabetic Periodontal Bone Repair

Diabetes aggravates the risk and severity of periodontitis, making the treatment of periodontitis in diabetic patients (DP) a significant challenge. Intestinal butyrate levels are critical regulators of DP and a potential therapeutic target. Butyrate-producing engineered bacteria have been demonstrated as an effective strategy for intestinal butyrate delivery. This study aimed to evaluate the therapeutic effect of butyrate-producing engineered probiotic on diabetic periodontitis and analyze its effects on the "gut-bone axis". Four-week-old male C57BL/6 mice with streptozotocin-induced diabetes and ligature-induced periodontitis received engineered probiotic for 6 weeks (approved by the Animal Ethics Committee). Periodontal repair was assessed via micro-CT and H&E staining. Gut microbiota (16S rRNA), serum cytokines (ELISA), Th17/Treg balance (flow cytometry), and metabolites (LC-MS) were analyzed. The results confirmed that the engineered bacteria treated group exhibited significant increases in periodontal bone mass, bone density (BMD), bone volume (BV), trabecular volume fraction (BV/TV), and trabecular thickness (P < 0.05). Serum inflammatory cytokine levels decreased significantly, and the balance of Th17 cells and Treg cells shifted toward an anti-inflammatory phenotype in immune organs (P < 0.05). 16S rRNA sequencing and untargeted metabolomics revealed that engineered bacterial treatment alleviated dysbiosis induced by diabetic periodontitis, promoted the proliferation of beneficial bacteria, and elevated serum levels of metabolites such as Camellimidazole B (P < 0.05). This study demonstrates that engineered probiotic mitigate diabetic alveolar bone loss by restoring gut homeostasis, attenuating systemic inflammation, and promoting osteogenesis.