Mapping the subgingival HerBiome and HisBiome over the human healthspan.

backgroundUnderstanding the intricate relationship between sex, age, and the oral microbiome is crucial for deciphering the onset and progression of numerous age-related oral and systemic diseases.

methodsSubgingival plaque was collected from 781 periodontally and systemically healthy females and 160 males spanning 0 to 80 years. 16S amplicon sequencing was performed. 80 million sequences were annotated and analyzed through the QIIME pipeline, principal components analysis (PCA) used for dimensionality reduction, LefSe to identify driver species, beta dispersion to measure inter-subject variability, and machine learning algorithm (RandomForest package in R [RF]) to validate the results. Causal mediation models were implemented to investigate the influence of aging on the male and female microbiomes.

resultsPCA demonstrated significant class separation based on sex (p < 0.001, permutational multivariate analysis of variance [PERMANOVA]). Males demonstrated higher alpha diversity (p < 0.001, Wilcoxon signed-rank test of the Shannon diversity index), but also higher inter-subject heterogeneity p < 0.001, ANOVA). RF identified males with 0.99 sensitivity, 0.15 specificity, and accuracy of 85%. Age exerted an almost complete mediation effect, with significant differences in the trajectory and pattern of aging between males and females. Females > 30 demonstrated a lower microbial diversity (p < 0.001) and higher levels of Fusobacterium nucleatum (p < 0.001), while the male microbiome remained highly personalized throughout the lifespan, without defined patterns of aging.

conclusionsSex and age interact to influence the subgingival microbiome. These findings might explain differing disease susceptibilities in either sex, as well as informing personalized prevention and intervention based on age and sex. Further studies using granular -omics approaches are needed to advance our knowledge. PLAIN LANGUAGE SUMMARY: Periodontal (gum) diseases are caused by a breakdown in the intricate balance between bacteria that live under the gumline and the local immune response. Since periodontal diseases have been reported to be more common in men than in women, we set out to investigate whether these bacterial communities are intrinsically different between the 2 sexes, and whether these differences are sustained over the lifespan. Using deep-sequencing technology to analyze the microbiomes of 941 individuals, we discovered that sex at birth is indeed a determining factor in the types of bacteria that live under the gums. Aging trajectories and patterns also differ between men and women, with women demonstrating a distinct shift after 30 years of age, and men showing no definite age-based change. These findings have important implications for the cause of periodontitis in either sex, as well as the potential to personalize therapy based on age and sex.