Periodontitis may impair the homeostasis of systemic bone through regulation of gut microbiota in ApoE−/− mice

Abstract Aim To investigate whether periodontitis impacts bone homeostasis via gut microbiota regulation. Materials and Methods Experimental periodontitis was induced by ligatures (LIG group). ApoE −/− mice were employed as a model with weakened bone homeostasis. Bone turnover was evaluated through micro‐computerized tomography, haematoxylin and eosin‐stained sections, osteoblast and osteoclast biomarkers in the bone and serum. Gut microbiota was analysed through 16S ribosomal RNA gene sequencing. Serum concentrations of cytokines were detected by enzyme‐linked immunosorbent assay. The role of gut microbiota was evaluated through their transplantation into antibiotic‐treated mice. Results Periodontitis significantly increased the number of osteoclasts and the expression of the osteoclast biomarkers in the proximal tibia of ApoE −/− mice, with the RANKL/OPG (receptor activator of nuclear factor‐κB ligand/osteoprotegerin) ratio significantly increased, which indicated the osteoclastic activity overwhelmed osteogenesis. Meanwhile, periodontitis altered the composition of gut microbiota and induced low‐grade inflammation in the colon and blood circulation. Interestingly, the concentration of circulating tumour necrosis factor‐α, interleukin (IL)‐6, IL‐1β, IL‐17A, and monocyte chemotactic factor‐1 were positively correlated with faecal α1‐antitrypsin and calprotectin, as well as serum OPG and RANKL. Furthermore, transplantation of gut microbiota from mice with periodontitis to antibiotic‐treated mice could partially re‐capitulate the phenotypes in the bone and colon. Conclusion Periodontitis may impair systemic bone homeostasis through gut microbiota.