Population genetic analyses of longitudinal vaginal microbiome reveal racioethnic evolutionary dynamics and prevailing positive selection of Lactobacillus adhesins

The vaginal microbiome is important for reproductive health and should constantly evolve in response to dynamic host-microbe interactions. The composition of the vaginal microbiome is associated with ethnicity; however, the evolutionary landscape of the vaginal microbiome, especially in the multi-ethnic context, remains under-studied. In this study, we performed a longitudinal evolutionary vaginal microbiome analysis of 351 samples from 35 pregnant women with diverse ethnic backgrounds and validated the main findings in two cohorts totaling 462 samples from 90 multi-ethnic women. Microbiome alpha diversity and community states showed strong ethnic signatures. Lactobacillaceae species had a significantly higher nonsynonymous/synonymous mutation ratio (pN/pS) than non-Lactobacillaceae species in all ethnicities. In addition, non-Lactobacillaceae anaerobic bacteria were enriched in Black and Latino women, with significantly elevated nucleotide diversity and lower pN/pS in Black women. Intriguingly, the Lactobacillaceae species had a large repertoire of positively selected genes, including the human mucin-binding and bacterial cell wall anchor genes, which showed independent, recurrent signatures of positive selection across multiple strains, indicating that the host-microbiome interactions directly drive microbial evolution at the molecular interface. Finally, we propose that the evolutionary metrics reflect the environmental niches of adapting microbes. Our study revealed the extensive ethnic signatures in vaginal microbial diversity, composition, community state, and evolutionary dynamics at species and gene levels, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective. HighlightsO_LIExtensive ethnic signatures in the vaginal microbial diversity, composition, community state, and evolutionary dynamics were demonstrated. C_LIO_LIHealthy Lactobacillaceae species showed lower nucleotide diversity but much more relaxed or even positive selection of genes than non-Lactobacillaceae species. C_LIO_LIIn Black women, non-Lactobacillaceae species displayed higher nucleotide diversity and more stringent negative selection. C_LIO_LILactobacillus mucin-binding and cell wall anchor genes showed convergent signatures of positive selection across vaginal microbiomes. C_LI