AUTHOR=Rahman Nuzhat , Mian M. Firoz , Nazli Aisha , Kaushic Charu 

TITLE=Human vaginal microbiota colonization is regulated by female sex hormones in a mouse model

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1307451

DOI=10.3389/fcimb.2023.1307451

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p>Clinically, a <italic>Lactobacillus</italic> rich vaginal microbiota (VMB) is considered optimal for reproductive outcomes, while a VMB populated by anaerobes is associated with dysbiosis and the clinical condition bacterial vaginosis (BV), which is linked to increased susceptibility to sexually transmitted infections and adverse reproductive outcomes. Mouse models that mimic eubiotic and dysbiotic VMB are currently lacking but could play a critical role in improving protective interventions.</p></sec><sec><title>Methods</title><p>In this study, probiotic, eubiotic, and dysbiotic models were developed in C57BL/6 mice, using probiotic strains <italic>Lactobacillus rhamnosus</italic> GR-1 and <italic>Lactobacillus reuteri</italic> RC-14, eubiotic <italic>Lactobacillus crispatus</italic>, or dysbiotic <italic>Gardnerella vaginalis</italic> strains. Endogenous sex hormones were manipulated by either ovariectomizing (OVX) mice or administering 17β-estradiol or progesterone pellets in OVX mice. Hormone-altered mice were inoculated with probiotic <italic>Lactobacillus</italic> species, <italic>L. crispatus</italic>, or <italic>G. vaginalis</italic>, and colonization was tracked using quantitative plating assays. Glycogen and MUC-1 levels in hormone-treated mice were determined with ELISA and MUC-1 staining.</p></sec><sec><title>Results</title><p>Following a single administration, <italic>L. rhamnosus</italic> and <italic>L. reuteri</italic> persisted in the mouse vaginal tract for up to eight days, <italic>L. crispatus</italic> persisted for up to three days, and <italic>G. vaginalis</italic> persisted for up to two days, as measured by quantitative plating assays and qPCR. Colonization of <italic>G. vaginalis</italic> was facilitated by the presence of mucin. The lack of endogenous hormones in OVX mice dramatically decreased VMB bacterial load compared to normal mice. None of the exogenous bacteria including <italic>Lactobacilli</italic> could colonize OVX mice for more than 24 hours. Treatment with 17β-estradiol but not progesterone restored the endogenous VMB and colonization with <italic>Lactobacilli</italic> and <italic>G. vaginalis</italic>. Interestingly, 17β-estradiol treated mice had significantly increased levels of glycogen compared to OVX and progesterone-treated mice. </p></sec><sec><title>Discussion</title><p>Based on the results, we have shown that estrogen played a significant role in the ability for human VMB species to colonize in our mouse models, potentially through a glycogen mediated mechanism. These results suggest there is a dynamic interaction between sex hormones and the VMB, which can affect bacterial diversity and the ability for a VMB to colonize.</p></sec>