Interactions between microbiota and cervical epithelial, immune, and mucus barrier

Abstract

The female reproductive tract harbours hundreds of bacterial species and produces numerous metabolites. The uterine cervix is located between the upper and lower parts of the female genital tract. It allows sperm and birth passage and hinders the upward movement of microorganisms into a relatively sterile uterus. It is also the predicted site for sexually transmitted infection (STI), such as Chlamydia, human papilloma virus (HPV), and human immunodeficiency virus (HIV). The healthy cervicovaginal microbiota maintains cervical epithelial barrier integrity and modulates the mucosal immune system. Perturbations of the microbiota composition accompany changes in microbial metabolites that induce local inflammation, damage the cervical epithelial and immune barrier, and increase susceptibility to STI infection and relative disease progression. This review examined the intimate interactions between the cervicovaginal microbiota, relative metabolites, and the cervical epithelial-, immune-, and mucus barrier, and the potent effect of the host-microbiota interaction on specific STI infection. An improved understanding of cervicovaginal microbiota regulation on cervical microenvironment homeostasis might promote advances in diagnostic and therapeutic approaches for various STI diseases.

Keywords: cervicovaginal microbiota; chlamydia trachomatis; epithelial; human immunodeficiency virus; human papilloma virus; immune; mucus; uterine cervix.

Figure 1

A healthy Lactobacillus dominant microbiota and the acidic environment formed by the associated metabolites especially lactic acid maintain cervical epithelial barrier integrity, stabilise the mucosal immune system. In contrast, microbiota dysbiosis and its accompanying changes in microbial metabolites can 1) damage mucus layer; 2) imbalance immune system: promote immune cells differentiate towards proinflammatory type and induce pro- and inflammatory cytokines secretion; 3) disrupt cervical epithelial barrier: induce inflammation reaction, oxidative stress, miRNA alteration of cervical epithelial cell, decrease intracellular junctions, and promote cell cycle arrest, apoptosis, and necrosis. Thus, increase the epithelial permeability and disrupt barrier function.