Researchers have reported that salivary microbiota associated with periodontitis influenced bone metabolism in a mouse model of osteoporosis through changes in the gut microbiota and microbial metabolites. The findings were published in the International Journal of Oral Science.
The investigators analyzed salivary microbiota from 21 patients with periodontitis and 17 periodontally healthy donors using 16S ribosomal RNA sequencing. The analysis showed that the periodontitis group had greater microbial diversity and enrichment of periodontal pathogens compared with healthy controls.
To examine systemic effects, the researchers administered pooled salivary microbiota from each group to ovariectomized mice through oral gavage. Using micro-computed tomography and histological analysis, the researchers observed that mice receiving microbiota from patients with periodontitis had lower bone mineral density and deteriorated trabecular architecture compared with mice receiving microbiota from healthy donors. Histological analyses also showed increased numbers of osteoclasts.
Further analyses examined whether gut microbial changes contributed to these skeletal effects. Sequencing of intestinal microbiota showed differences in microbial community composition between groups. Fecal microbiota transplantation experiments indicated that transferring gut microbiota from mice exposed to periodontitis-associated salivary microbiota reproduced bone loss in recipient mice.
Metabolomic analysis of intestinal contents and serum identified differences in metabolic pathways between groups, including reduced activity in tryptophan metabolism. Levels of indole-3-lactic acid (ILA), a metabolite derived from tryptophan, were reduced in mice exposed to periodontitis-associated microbiota.
Laboratory experiments using bone-marrow–derived macrophages showed that ILA inhibited osteoclast differentiation. In additional experiments, oral administration of ILA to mice receiving periodontitis-associated microbiota increased bone density measures and reduced osteoclast numbers.
In a press release, co-author Fuhua Yan said, “[t]his study shows that oral health cannot be viewed in isolation from systemic physiology,” and continued, “[w]e were motivated by the clinical reality that many patients suffer simultaneously from periodontal disease and osteoporosis, yet treatment strategies rarely consider their biological connection.”
“Our findings suggest that targeting gut microbial metabolism could open new preventive and therapeutic avenues in the future,” said co-author Fangfang Sun.
The researchers noted several study limitations, including a limited clinical sample size, and stated that further studies are needed to investigate the underlying mechanisms.
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