Cervicovaginal Microbiome and Urine Metabolome Paired Analysis Reveals Niche Partitioning of the Microbiota in Patients with Human Papilloma Virus Infections.

Nataliya Chorna,Filipa Godoy-Vitorino,Josefina Romaguera

doi:10.3390/metabo10010036

Nataliya Chorna, Filipa Godoy-Vitorino + Show 1 more

Open Access

https://doi.org/10.3390/metabo10010036

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Journal: Metabolites	Publication Date: Jan 15, 2020
Citations: 24	License type: CC BY 4.0

Affiliation: University of Puerto Rico System

Abstract

In this study, we evaluate the association between vaginal and cervical human papillomavirus infections high-risk types (HPV+H), negative controls (HPV−), the bacterial biota, and urinary metabolites via integration of metagenomics, metabolomics, and bioinformatics analysis. We recently proposed that testing urine as a biofluid could be a non-invasive method for the detection of cervical HPV+H infections by evaluating the association between cervical HPV types and a total of 24 urinary metabolites identified in the samples. As a follow-up study, we expanded the analysis by pairing the urine metabolome data with vaginal and cervical microbiota in selected samples from 19 Puerto Rican women diagnosed with HPV+H infections and HPV− controls, using a novel comprehensive framework, Model-based Integration of Metabolite Observations and Species Abundances 2 (MIMOSA2). This approach enabled us to estimate the functional activities of the cervicovaginal microbiome associated with HPV+H infections. Our results suggest that HPV+H infections could induce changes in physicochemical properties of the genital tract through which niche partitioning may occur. As a result, Lactobacillus sp. enrichment coincided with the depletion of L. iners and Shuttleworthia, which dominate under normal physiological conditions. Changes in the diversity of microbial species in HPV+H groups influence the capacity of new community members to produce or consume metabolites. In particular, the functionalities of four metabolic enzymes were predicted to be associated with the microbiota, including acylphosphatase, prolyl aminopeptidase, prolyl-tRNA synthetase, and threonyl-tRNA synthetase. Such metabolic changes may influence systemic health effects in women at risk of developing cervical cancer. Overall, even assuming the limitation of the power due to the small sample number, our study adds to current knowledge by suggesting how microbial taxonomic and metabolic shifts induced by HPV infections may influence the maintenance of microbial homeostasis and indicate that HPV+H infections may alter the ecological balance of the cervicovaginal microbiota, resulting in higher bacterial diversity.

Highlights

Discoveries resulting from human microbiome research have demonstrated that microbes play a role in the susceptibility to HPV and neoplasia [1,2,3]
Even assuming the limitation of the power due to the small sample number, our study adds to current knowledge by suggesting how microbial taxonomic and metabolic shifts induced by HPV infections may influence the maintenance of microbial homeostasis and indicate that human papillomavirus infections high-risk types (HPV+H) infections may alter the ecological balance of the cervicovaginal microbiota, resulting in higher bacterial diversity
In Mexican women, Sneathia spp. were considered cervical biomarkers for neoplasia [14], while in Puerto Ricans, a loss in Lactobacillus was associated with an increase in Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions with HPV+H, low-risk HPV, or both co-infections [2]

Summary

Introduction

Discoveries resulting from human microbiome research have demonstrated that microbes play a role in the susceptibility to HPV and neoplasia [1,2,3]. Oncogenic high-risk human papilloma virus (HPV+H) infections are associated with the development of carcinomas, a malignancy on the rise in multiple populations [4,5,6]. Oncogenic high-risk human papilloma virus (HPV+H) infections are Metabolites 2020, 10, 36; doi:10.3390/metabo10010036 www.mdpi.com/journal/metabolites. Metabolites 2020, 10, 36 associated with the development of carcinomas, a malignancy on the rise in multiple populations [4,5,6]. In Mexican women, Sneathia spp. were considered cervical biomarkers for neoplasia [14], while in Puerto Ricans, a loss in Lactobacillus was associated with an increase in Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions with HPV+H, low-risk HPV, or both co-infections [2].

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