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.

Keywords: bone homeostasis; gut microbiota; periodontitis; systemic inflammation.