The Cervicovaginal Microbiota-Host Interaction Modulates Chlamydia trachomatis Infection

The mechanism(s) by which -dominated cervicovaginal microbiota provide a barrier to infection remain(s) unknown. Here we evaluate the impact of different spp. identified via culture-independent metataxonomic analysis of -infected women on infection in a three-dimensional (3D) cervical epithelium model. spp. that specifically produce d(-) lactic acid were associated with long-term protection against infection, consistent with reduced protection associated with , which does not produce this isoform, and with decreased epithelial cell proliferation, consistent with the observed prolonged protective effect. Transcriptomic analysis revealed that epigenetic modifications involving histone deacetylase-controlled pathways are integral to the cross talk between host and microbiota. These results highlight a fundamental mechanism whereby the cervicovaginal microbiota modulates host functions to protect against infection. The vaginal microbiota is believed to protect women against , the etiologic agent of the most prevalent sexually transmitted infection (STI) in developed countries. The mechanism underlying this protection has remained elusive. Here, we reveal the comprehensive strategy by which the cervicovaginal microbiota modulates host functions to protect against chlamydial infection, thereby providing a novel conceptual mechanistic understanding. Major implications of this work are that (i) the impact of the vaginal microbiota on the epithelium should be considered in future studies of chlamydial infection and other STIs and (ii) a fundamental understanding of the cervicovaginal microbiota's role in protection against STIs may enable the development of novel microbiome-based therapeutic strategies to protect women from infection and improve vaginal and cervical health.