Correlation between oral microbial characteristics and overall bone density of Postmenopausal women based on macrogenomic analysis

Background Postmenopausal osteoporosis (PMO), a prevalent bone disease triggered by estrogen deficiency - induced bone mass reduction and deterioration of bone tissue microarchitecture, escalates the risk of fragility fractures. Recent research has highlighted the pivotal role of oral and gut microbiota in PMO development, giving rise to the “oral - gut - bone axis” concept. Methods A total of 21 postmenopausal women, aged 50 - 60, were recruited for the study. Based on bone mineral density (BMD) measurements from dual - energy X - ray absorptiometry (DXA), participants were divided into osteopenia, osteoporosis, and healthy groups. Saliva and dental plaque samples were collected for metagenomic sequencing to analyze microbial diversity and community composition, with differences identified via LEfSe analysis. KEGG pathway analysis was used to reveal variations in microbial functions. Based on these analyses, predictive models for bone density status were constructed using LASSO regression and random forest algorithms. Results Significant differences in salivary microbial community structures were found between the osteoporosis and healthy groups (P = 0.041). LEfSe analysis revealed higher abundance of Aggregatibacter, Haemophilus haemolyticus, Haemophilus sputorum, Pasteurellaceae, Neisseria elongata, Aggregatibacter segnis, and Aggregatibacter aphrophilus in the osteopenia group, and higher abundance of Streptococcus pneumoniae and Haemophilus paraphrohaemolyticus in the osteoporosis group compared to the healthy group. The random forest models for osteopenia vs. healthy and osteoporosis vs. healthy yielded AUC values of 0.82 and 0.74, respectively, suggesting potential predictive capability, though further validation in larger cohorts is needed to confirm their generalizability. Functional analysis using LEfSe identified differential KEGG pathways, including glycan biosynthesis and metabolism in cancer, choline metabolism in cancer, and the cGMP-PKG signaling pathway. Conclusion This exploratory study utilized metagenomic sequencing to analyze the relationship between oral microbiota and PMO while controlling for key confounders. We identified significant compositional and functional alterations in the oral microbiome associated with bone mineral density status, including specific bacterial species showing marked intergroup differences. A model based on differential microbial features exhibited preliminary discriminative capacity, and functional analysis suggested involvement of inflammatory and metabolic pathways. These findings provide initial evidence linking oral microbiota to PMO.