Periodontitis is a chronic inflammatory disease of the gums that affects hundreds of millions of people worldwide and is increasingly associated with systemic diseases beyond the oral cavity. Although epidemiological studies have long suggested an association between periodontitis and osteoporosis, particularly in postmenopausal women, the biological mechanisms linking these conditions remain unclear. There is growing evidence that microbial communities play a central role in regulating immune responses and metabolism across distant organs, raising the possibility that oral microbes influence bone health through indirect pathways.
To investigate this possibility, a research team led by Professor Fuhua Yan and researcher Dr. Fangfang Sun from Nanjing Stomatology Hospital, Nanjing University Institute of Stomatology Medical College Hospital, was formed. Researchers analyzed the salivary microbiota of people with advanced periodontitis and compared them with samples from healthy donors with periodontitis. They then administered this microbiota to ovariectomized mice, an established model of postmenopausal osteoporosis. This approach allowed the team to isolate the influence of the oral microbial community without disrupting inflammatory factors. Their discovery is International Journal of Oral Sciences January 27, 2026.
Using high-resolution micro-CT imaging and histological analysis, the researchers observed that mice that received salivary microbiota from periodontitis patients had significantly reduced bone density and worsened trabecular structure compared to controls. These skeletal changes were accompanied by a marked increase in the number of osteoclasts, indicating enhanced bone resorption.
Further investigation revealed that these bone effects are mediated through the intestine. Although periodontal pathogens themselves did not predominately colonize the intestine, the salivary microbiota of periodontitis patients reshaped the intestinal microbial ecosystem. Fecal microbiota transplantation experiments confirmed that abnormalities in the gut microbiota alone were sufficient to reproduce bone loss in recipient mice. Metabolomic analysis of intestinal contents and serum showed that tryptophan metabolism was significantly suppressed, highlighting microbial metabolites as important signaling molecules in the oral-gut-bone axis.
Among the altered metabolites, indole-3-lactic acid (ILA) emerged as an important protective factor. ILA levels were significantly reduced in mice exposed to periodontitis-associated microbiota. In cell-based experiments, ILA directly inhibited the differentiation and activity of osteoclasts, which are responsible for bone resorption. Oral administration of ILA to affected mice restored bone density, improved trabecular structure, significantly reduced osteoclast numbers, and effectively reversed skeletal damage.
“This study shows that oral health cannot be considered in isolation from systemic physiology.” said Professor Yang. “We were motivated by the clinical reality that many patients suffer from periodontal disease and osteoporosis at the same time, yet treatment strategies rarely take their biological association into account.”
Dr. Sun added: “Our findings suggest that targeting gut microbial metabolism may open new avenues for prevention and treatment in the future, not only for osteoporosis but also for other systemic diseases affected by chronic oral inflammation.”
In the short term, this study highlights the importance of maintaining oral health as part of osteoporosis risk management and suggests that microbial metabolites may serve as early biomarkers or targets for intervention. In the long term, understanding how oral microbes regulate gut metabolism may enable microbiome-based treatments that reduce fracture risk and improve quality of life in older adults. This research also paves the way for interdisciplinary collaboration between dentistry, microbiology, metabolomics, and bone biology, potentially reshaping the way we prevent and treat systemic diseases associated with chronic inflammation.
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Reference magazines:
Wang N. others. (2026). Periodontitis-associated salivary microbiota exacerbates systemic osteoclastogenesis through intestinal regulation and suppressed tryptophan metabolism in ovariectomized mice. International Journal of Oral Sciences. DOI: 10.1038/s41368-025-00415-2. https://www.nature.com/articles/s41368-025-00415-2
