Abstract
BackgroundThe composition of the microbiome plays an important role in human health and disease. Whether there is a direct association between the cervicovaginal microbiome and the host’s epigenome is largely unexplored.ResultsHere we analyzed a total of 448 cervicovaginal smear samples and studied both the DNA methylome of the host and the microbiome using the Illumina EPIC array and next-generation sequencing, respectively. We found that those CpGs that are hypo-methylated in samples with non-lactobacilli (O-type) dominating communities are strongly associated with gastrointestinal differentiation and that a signature consisting of 819 CpGs was able to discriminate lactobacilli-dominating (L-type) from O-type samples with an area under the receiver operator characteristic curve (AUC) of 0.84 (95% CI = 0.77–0.90) in an independent validation set. The performance found in samples with more than 50% epithelial cells was further improved (AUC 0.87) and in women younger than 50 years of age was even higher (AUC 0.91). In a subset of 96 women, the buccal but not the blood cell DNA showed the same trend as the cervicovaginal samples in discriminating women with L- from O-type cervicovaginal communities.ConclusionsThese findings strongly support the view that the epithelial epigenome plays an essential role in hosting specific microbial communities.
Highlights
The composition of the microbiome plays an important role in human health and disease
We found that methylation differences vary due to immune cell-type composition in cases compared to controls [14, 15], and it is important to assess the level of cell-type heterogeneity in each cervical smear sample as a first step in the analysis pathway
The total immune cell proportion was not associated with microbiota community-type (ROC AUC in the validation set was 0.53, 95% CI = 0.43–0.63)
Summary
The composition of the microbiome plays an important role in human health and disease. The microbiome plays an essential role in human health and disease, with its composition being one of the most important factors. The physiological cervicovaginal microbiome is dominated by four types of Lactobacilli: L crispatus, L gasseri, L iners and L jensenii [12, 13]. These Lactobacilli are associated with a substantially lower vaginal pH [12], potentially decreasing the risk of ascending infections. The presence of ovarian cancer or factors that have been proven to affect the risk of this cancer, such as BRCA1 germline mutations, were significantly associated with the community-type O cervicovaginal microbiota [4]
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