Abstract
Disease states are often linked to large scale changes in microbial community structure that obscure the contributions of individual microbes to disease. Establishing a mechanistic understanding of how microbial community structure contribute to certain diseases, however, remains elusive thereby limiting our ability to develop successful microbiome-based therapeutics. Human microbiota-associated (HMA) mice have emerged as a powerful approach for directly testing the influence of microbial communities on host health and disease, with the transfer of disease phenotypes from humans to germ-free recipient mice widely reported. We developed a HMA mouse model of the human vaginal microbiota to interrogate the effects of Bacterial Vaginosis (BV) on pregnancy outcomes. We collected vaginal swabs from 19 pregnant African American women with and without BV (diagnosed per Nugent score) to colonize female germ-free mice and measure its impact on birth outcomes. There was considerable variability in the microbes that colonized each mouse, with no association to the BV status of the microbiota donor. Although some of the women in the study had adverse birth outcomes, the vaginal microbiota was not predictive of adverse birth outcomes in mice. However, elevated levels of pro-inflammatory cytokines in the uterus of HMA mice were detected during pregnancy. Together, these data outline the potential uses and limitations of HMA mice to elucidate the influence of the vaginal microbiota on health and disease.
Highlights
The vagina houses a numerically immense and functionally consequential microbiota (Mendling, 2016; Kaminska and Gajecka, 2017)
19 pregnant African American women were recruited and information pertaining to Nugent score of vaginal swab were collected at the same time as the microbiota sample, while patient demographics, health status, pregnancy complications and birth outcomes were recorded as well (Table 1)
Seven women presented with a normal Nugent score between 0 and 3, four women presented with an intermediate Nugent score between 4 and 6, and eight women presented with a Nugent score of 7 or higher indicative of Bacterial Vaginosis (BV) (Table 1)
Summary
The vagina houses a numerically immense and functionally consequential microbiota (Mendling, 2016; Kaminska and Gajecka, 2017). Distinct anatomic regions within the female reproductive tract house a dynamically changing microbial community of vastly different numbers and taxonomic composition It is well-known that the vagina maintains a numerically vast microbiota while the uterus (pregnant and non-pregnant) is normally colonized with very limited microbiota (Aagaard et al, 2014; Franasiak and Scott, 2017). HMA Mice for Vaginal Microbiota and consequences of the unique lactobacilli-dominant community structure remains enigmatic, though it is generally accepted that lactate produced by these bacteria results in the characteristic acidic pH of the healthy vagina This is a result of direct or syntrophic fermentation of the abundant glycogen found in apical squamous epithelia of the vagina (Charbonneau et al, 2016; Reid, 2016). The female reproductive tract has a highly adapted microbiota with known beneficial effects including colonization resistance against pathogens (Sykiotis and Bohmann, 2008)
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