Hyperglycemia and systemic inflammation differentially shape immune dysregulation, tissue destruction, and microbiota in experimental periodontitis and peri-implantitis in diabetic mice

Aim To investigate the impact of hyperglycemia and systemic inflammation on experimental periodontitis/peri-implantitis in diabetic mice, focusing on osteoimmunological dysregulation and oral microbial alteration. Materials and methods After implant placement, diabetic db/db mice were treated with Liraglutide, Indomethacin, or both, followed by ligature-induced experimental periodontitis/peri-implantitis. Samples were analyzed for bone loss, inflammatory cytokines, osteoclast activity, RAGE expression, IL-17-associated inflammatory responses, and Treg infiltration. The periodontal/peri-implant microbiota were examined by metagenomics and tested in vitro for inflammatory cytokine induction. Results Liraglutide, but not indomethacin, effectively reduced bone loss, immune cell infiltration, RAGE, IL-17A expression, and restored Foxp3 + Treg presence. Post-treatment cytokine responses were slightly different between peri-implantitis sites compared to those in periodontitis sites. Oral microbiota composition from diabetic mice differed significantly from that of normoglycemic mice. Liraglutide treatment produced the greatest deviation from the ligation-only profile and shifted the microbiome toward normoglycemic control. The peri-implant microbiome was more resistant to interventions than the periodontal communities. Hyperglycemia control alleviated microbiome-induced pro-inflammatory responses in vitro . Conclusions Diabetic hyperglycemia is a more predominant driver than systemic inflammation in exacerbating periodontitis/peri-implantitis tissue destruction, immune dysregulation, and eliciting a pro-inflammatory oral microbial environment. The local inflammatory response and microbial alteration around the tooth and implant were similar but not identical.