Diabetes exacerbates experimental peri-implantitis in mice with elevated IL-17A-associated inflammation and IL-17F upregulation

This study investigated the role of interleukin-17 (IL-17) and the oral microbiome in peri-implant inflammation and bone loss under hyperglycemic and normoglycemic conditions. Wild-type (WT) and diabetic (db/db) mice with maxillary implants underwent ligature placement with or without IL-17A neutralization. Bone loss, osteoclast activity, inflammatory cytokines, Th17/Treg balance, and expression of IL-17Family members were analyzed. The oral microbiota was profiled by 16S rRNA sequencing, and its inflammatory potential was evaluated by co-culture with immune cells. Diabetic db/db mice exhibited greater peri-implant bone loss, osteoclast numbers, and RANKL/OPG ratios than WT, accompanied by elevated Il17a expression, reduced anti-inflammatory cytokines, enhanced Th17-associated inflammatory features, and altered FOXP3⁺ cell profiles. IL-17A neutralization significantly attenuated, but did not fully normalize, heightened inflammatory responses in db/db mice, whereas ligature-induced Il17f upregulation was observed only in db/db mice. Microbial alterations were partially shifted toward control profiles by IL-17A inhibition in WT mice, while diabetes-associated changes persisted regardless of ligation or anti-IL-17A. In vitro, peri-implant microbiota induced pro-inflammatory cytokine responses in splenocytes, with residual inflammatory responses remaining more evident in DB-derived microbiota after IL-17A inhibition. These findings suggest that peri-implantitis in diabetes is exacerbated by heightened IL-17-mediated inflammation and persistent microbial alterations, underscoring the need for more comprehensive therapeutic approaches to address the disease under diabetic conditions.