Host and Microbiome Interplay Shapes the Vaginal Microenvironment

Abstract

The female reproductive tract harbors a unique microbiome, especially the vagina. The human vaginal microbiome exhibits a low diversity and is dominated by Lactobacillus species, compared to the microbiome of other organs. The host and vaginal microbiome mutually coexist in the vaginal microenvironment. Host cells provide Lactobacillus glycogen as an energy source, and Lactobacillus produce lactic acid, which lowers vaginal pH thereby preventing growth of other bacteria. Bacterial vaginosis can modulate host immune systems, and is frequently associated with various aspects of disease, including sexually transmitted infection, gynecologic cancer, and poor pregnancy outcomes. Because of this, numerous studies focused on the impact of the vaginal microbiome on women`s health and disease. Furthermore, numerous epidemiologic studies also have demonstrated various host factors regulate the vaginal microbiome. The female reproductive tract undergoes constant fluctuations due to hormonal cycle, pregnancy, and other extrinsic factors. Depending on these fluctuations, the vaginal microbiome composition can shift temporally and dynamically. In this review, we highlight the current knowledge of how host factors modulate vaginal microbiome composition and how the vaginal microbiome contributes to maintaining homeostasis or inducing pathogenesis. A better understanding of relationship between host and vaginal microbiome could identify novel targets for diagnosis, prognosis, or treatment of microbiome-related diseases.

Keywords: STI; bacterial vaginosis; estrogen; glycogen; lactobacillus; preterm birth; probiotics; vaginal microbiome.

Figure 1

Various intrinsic and extrinsic factors that affect vaginal microbial community. The composition of the vaginal microbiome differs across host predisposing factors, such as race, ethnicity, and genetic variation. Lifestyle factors including diet, sexual behavior, hygienic practice, contraceptives, smoking, stress, and obesity also affect vaginal microbiome composition. Particularly, Lactobacillus abundance changes by level of glycogen, which deposits in epithelial cells upon estrogen stimulation. Prepubertal girls and postmenopausal women have relatively low abundance of lactobacillus species.

Figure 2

Host immune system and microbiome. (A) Lactobacillus crispatus produce both L- and D-lactic acid to protect the host against pathogens. Lactobacillus crispatus also can produce hydrogen peroxide (H2O2) in vitro, however it’s antimicrobial role in vivo is controversial. Innate immune cells and epithelial cells produce antimicrobial peptides (AMPs), such as secretory leukocyte protease inhibitors (SLPIs), elafin, calprotectin, lysozyme and defensins. Immunoglobulin (Ig)G and IgA from memory B cells also contribute to protection. Lactobacillus iners produce only L-lactic acid, and inerolysin from Lactobacillus iners can damage host epithelial cells. (B) Bacterial vaginosis (BV) is associated with various gynecologic and obstetric diseases. In BV, the vaginal microbiome is dominated by diverse anaerobe bacteria, including Gardnerella and Prevotella. These bacteria form biofilm, which confers resistance to antibiotics, lactic acid, and H₂O₂. BV-associated bacteria also produce sialidase and vaginolysin. Sialidase cleaves mucin, and vaginolysin damages host epithelial cells. BV induces proinflammatory response. IL-33 produced by epithelial cells directly inhibits effector CD4 and CD8 T cells during herpes simplex virus (HSV)-2 infection. Meanwhile, BV increases predisposing CD4 T cells and increases risk of human immunodeficiency virus (HIV) acquisition.