The metagenome of the female upper reproductive tract

Abstract

BackgroundThe human uterus is traditionally believed to be sterile, while the vaginal microbiota plays an important role in fending off pathogens. Emerging evidence demonstrates the presence of bacteria beyond the vagina. However, a microbiome-wide metagenomic analysis characterizing the diverse microbial communities has been lacking.ResultsWe performed shotgun-sequencing of 52 samples from the cervical canal and the peritoneal fluid of Chinese women of reproductive age using the Illumina platform. Direct annotation of sequencing reads identified the taxonomy of bacteria, archaea, fungi and viruses, confirming and extending the results from our previous study. We replicated our previous findings in another 24 samples from the vagina, the cervical canal, the uterus and the peritoneal fluid using the BGISEQ-500 platform revealing that microorganisms in the samples from the same individuals were largely shared in the entire reproductive tract. Human sequences made up more than 99% of the 20GB raw data. After filtering, vaginal microorganisms were well covered in the generated reproductive tract gene catalogue, while the more diverse upper reproductive tract microbiota would require greater depth of sequencing and more samples to meet the full coverage scale.ConclusionsWe provide novel detailed data on the microbial composition of a largely unchartered body site, the female reproductive tract. Our results indicated the presence of an intra-individual continuum of microorganisms that gradually changed from the vagina to the peritoneal fluid. This study also provides a framework for understanding the implications of the composition and functional potential of the distinct microbial ecosystems of the female reproductive tract in relation to health and disease.

The vagino-cervical microbiome as a woman’s life history

“…By reaching to the cervix with a cytobrush, reflecting both the upper and the lower reproductive tract (Chen et al, 2017; Li et al, 2018), we show here that the association with the fecal microbiome was scarce overall, and the notion of reservoirs in the intestine or other sites for vaginocervical bacteria (Marrazzo et al, 2012) would need further investigation, especially in light of individual differences in the number of CD4+ T cells in mucosal sites (Gosmann et al, 2017). There were other interesting associations between different species that potentially involve immune modulation (Fig.…”

“…While samples from multiple body sites (peritoneal fluid from the pouch of Douglas, fallopian tubes, endometrium, cervical mucus and two vaginal sites) were taken from volunteers with benign conditions such as hysteromyoma, adenomyosis and endometriosis (Chen et al, 2017; Li et al, 2018), we were only able to sample the vagino-cervical microbiome in this healthy cohort. Interestingly, our cohort generally lacked bacteria known for BV (e.g.…”

“…In the postmenopausal samples, some of the bacteria previously reported in the upper reproductive tract (Chen et al, 2017; Lee et al, 2019; Li et al, 2018) and involved in degradation of hormones (Wang et al, 2018b), e.g. Pseudomonas spp.…”

“…The presence of microorganisms beyond the cervix (i.e. the upper reproductive tract) is increasingly recognized even in non-infectious conditions (Aagaard et al, 2014; Chen et al, 2017; Li et al, 2018), with much debated implications for women’s and infants’ health.…”

“…How vaginal Lactobacilli interplay with Candida albicans and other related fungi is also an important question for preventing or treating vulvovaginal candidiasis (Bradford and Ravel, 2017). The over 90% of human sequences in female reproductive tract samples, in contrast to 1% in feces (Li et al, 2018; Methé et al, 2012; Wang and Jia, 2016), has made metagenomic shotgun sequencing more expensive. Most studies of the vaginal microbiota used 16S rRNA gene amplicon sequencing, which lacked a view of the overall microorganism communities including bacteria, archaea, viruses and fungi (Byrd et al, 2018), as well as the functional capacity encoded.…”