• The cervicovaginal microbiota-host interaction modulates chlamydia trachomatis infection

      Edwards, V.L.; Smith, S.B.; McComb, E.J.; Humphrys, M.S.; Gajer, P.; Gwilliam, K.; Terplan, M.; Mark, K.S.; Brotman, R.M.; Bavoil, P.M.; et al. (American Society for Microbiology, 2019)
      The mechanism(s) by which Lactobacillus-dominated cervicovaginal microbiota provide a barrier to Chlamydia trachomatis infection remain(s) unknown. Here we evaluate the impact of different Lactobacillus spp. identified via cultureindependent metataxonomic analysis of C. trachomatis-infected women on C. trachomatis infection in a three-dimensional (3D) cervical epithelium model. Lactobacillus spp. that specifically produce D(-) lactic acid were associated with long-term protection against C. trachomatis infection, consistent with reduced protection associated with Lactobacillus iners, 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 C. trachomatis infection. IMPORTANCE The vaginal microbiota is believed to protect women against Chlamydia trachomatis, 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. Copyright 2019 Edwards et al.
    • The vaginal microbiota, host defence and reproductive physiology

      Smith, S.B.; Ravel, J. (Blackwell Publishing Ltd, 2017)
      The interaction between the human host and the vaginal microbiota is highly dynamic. Major changes in the vaginal physiology and microbiota over a woman's lifetime are largely shaped by transitional periods such as puberty, menopause and pregnancy, while daily fluctuations in microbial composition observed through culture-independent studies are more likely to be the results of daily life activities and behaviours. The vaginal microbiota of reproductive-aged women is largely made up of at least five different community state types. Four of these community state types are dominated by lactic-acid producing Lactobacillus spp. while the fifth is commonly composed of anaerobes and strict anaerobes and is sometimes associated with vaginal symptoms. The production of lactic acid has been associated with contributing to the overall health of the vagina due to its direct and indirect effects on pathogens and host defence. Some species associated with non-Lactobacillus vaginal microbiota may trigger immune responses as well as degrade the host mucosa, processes that ultimately increase susceptibility to infections and contribute to negative reproductive outcomes such as infertility and preterm birth. Further studies are needed to better understand the functional underpinnings of how the vaginal microbiota affect host physiology but also how host physiology affects the vaginal microbiota. Understanding this fine-tuned interaction is key to maintaining women's reproductive health. (Figure presented.). Copyright 2016 The Authors.