Abstract

The vaginal microbiota plays an important role in women's reproductive and urogenital health. It is now well accepted that a "healthy" vaginal microbiome is dominated by Lactobacillus species. Disturbances in this microbial community can lead to several adverse outcomes, including pelvic inflammatory disease and bacterial vaginosis (BV), as well as increased susceptibility to sexually transmitted infections, miscarriage, and preterm births. However, vaginal communities, especially those of women in the developing world, can be comprised of a diverse set of microorganisms in the absence of overt clinical symptoms. The implications of these diverse vaginal microbiomes for women's health remain poorly understood. Rhesus macaques are an excellent translational animal model to address these questions due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive-age female rhesus macaques. At both the taxonomic and functional levels, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic Gram-negative bacteria, including Sneathia, Prevotella, Porphyromonas, and Mobiluncus Interestingly, some animals were transiently colonized by Lactobacillus and some with Gardnerella Our in-depth and comprehensive analysis highlights the importance of the model to understand the health implications of a diverse vaginal microbiome and test interventions for manipulating this community.IMPORTANCE It is widely accepted that the "healthy" vaginal microbiome of women in the developed world is dominated by Lactobacillus species. However, in the developing world, many asymptomatic women harbor diverse vaginal microbial communities that are typically associated with bacterial vaginosis. Many questions remain about the drivers and health implications of a diverse vaginal microbial community. Rhesus macaques provide an excellent translational model to address these questions due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from a large cohort of reproductive-age rhesus macaques. At the taxonomic, genomic, and functional levels, the rhesus macaque vaginal microbiome was most similar to that of humans, who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Our in-depth and comprehensive analysis highlights the utility of macaques as a model to study diverse vaginal community state types and test interventions for manipulating the vaginal microbiome.

Highlights

  • The vaginal microbiota plays an important role in women’s reproductive and urogenital health

  • Rhesus macaques display the clinical hallmarks of bacterial vaginosis (BV) and are colonized by a diverse vaginal microbiome

  • Profiling of the vaginal microbial (VM) communities using 16S rRNA gene amplicon sequencing showed a high relative abundance of bacterial taxa associated with BV, including Sneathia, Mobiluncus, Prevotella, and Gardnerella (Table 1)

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Summary

Introduction

The vaginal microbiota plays an important role in women’s reproductive and urogenital health. We performed a longitudinal analysis of clinical and microbiome data from 16 reproductive-age female rhesus macaques At both the taxonomic and functional levels, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Microbiome transfer procedures have recently come under scrutiny due to safety concerns [16, 17] Another potential intervention is the use of prebiotics as an inexpensive and accessible alternative to antibiotic treatment for BV [18, 19] to shift a microbial community to a more “beneficial” state. A study of rhesus macaques reported that maltose can shift diverse vaginal communities into Lactobacillus-dominated ones [22] This shift was short-lived, and the relative abundance of Lactobacillus species was .5% before treatment in the test group [22]. It is still unclear whether a sucrose intervention could improve clinical outcomes when the frequency of Lactobacillus species is extremely low, which Lactobacillus strains can respond to sucrose treatment, and how effective this intervention is

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