Vitamin D deficiency in mice modulates oral microbiome stability over time and leads to changes in host inflammatory gene expression pathways.

Abstract

INTRODUCTION: We previously showed that vitamin D deficiency leads to gingival inflammation and alveolar bone loss in mice, and that topical vitamin Dadministration prevents that bone loss and inflammation and fosters a health-associated oral microbiota in a murine ligature model of periodontal disease. To understand the relationship between vitamin D, the oral microbiome, and host factors, we performed taxonomic profiling of the oral microbiome from C57Bl/6 mice fed either a vitamin D-deficient diet or a standard diet. METHODS: This was a 13-week study, with a group crossover period at week 7. Oral microbiomes were sampled weekly. At the end of the 13 weeks, single-cell analysis was performed on the gingival and buccal tissues. RESULTS: During the first 6 weeks, the vitamin D-deficient group 1 showed higher diversity at the start of the experiments but was more volatile in alpha-diversity values, with a notable dip in diversity at week 8. Group 2 showed lower initial diversity but was more stable by mid-study and remained relatively higher during the period where group 1 diversity crashes (weeks 6-8). The most striking feature occurs around weeks 6-8, coinciding with the change in vitamin D diet, group 1 plummets while group 2 either remained stable or rose. DISCUSSION: This showed that elimination of vitamin Din the diet altered the diversification of bacterial species in favor of an oral microbiome associated with inflammation and bone loss. This persistent dysbiosis contrasts with the transcriptomic changes, which showed mice on a vitamin D deficient diet displayed an overall enrichment of gene sets involved in epithelial development, suggesting that re-introduction of vitamin D into the diet may help improve mucosal barrier health in the face of persistent microbiome dysbiosis.