DNA methylation signatures to predict the cervicovaginal microbiome status

DNA 甲基化特征预测宫颈阴道微生物组状态

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作者:Nuno R Nené, James Barrett, Allison Jones, Iona Evans, Daniel Reisel, John F Timms, Tobias Paprotka, Andreas Leimbach, Dorella Franchi, Nicoletta Colombo, Line Bjørge, Michal Zikan, David Cibula, Martin Widschwendter

Background

The 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.

Conclusions

These findings strongly support the view that the epithelial epigenome plays an essential role in hosting specific microbial communities.

Results

Here 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. Conclusions: These findings strongly support the view that the epithelial epigenome plays an essential role in hosting specific microbial communities.

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