Inter American University of Puerto Rico
“Metagenomics and Metabolomics on the female genital microbiota in relation to HPV”
Infections by genital human papillomavirus (HPV) are one of the world’s most commonly diagnosed sexually transmitted infections, and high-risk HPV types are strongly linked to cervical cancer.
The human cervicovaginal microbiota is an interface between the host and the environment and may play a role in susceptibility to HPV infections and neoplasia. The microbial community composition of the cervix of Puerto Rican women, and its relation to HPV infections and its metabolism has not been studied. In Puerto Rico, the prevalence of HPV is about 38%, slightly higher than the ~27% in the continental US, and no microbial ecology studies have been performed to address microbial susceptibility to infection. As such, understanding the composition, functional diversity and metabolism of the vaginal and cervical microbiome and HPV virome in Puerto Rican women, will be essential for comprehensively understanding the etiology and prevention of HPV infections.
This project explores the relationship between the cervicovaginal microbiome, HPV status, obesity and urinary estrogen metabolites, in Puerto Rican women ages 21-40.
I hypothesize that: 1) the microbial communities and their functions differ according to HPV status and 2) that genomic/metabolic profiles in cervicovaginal samples are impacted by obesity, and the estrogen milieu, likely involved in regulating the homeostasis of the microbiome and its resilience to infection.
To test these hypotheses, I have the following specific aims:
1. To perform in-depth phylogenetic analysis of the vaginal, cervical and anal microbial communities through 16S rRNA and fungal ITS sequencing in reproductive age Puerto Rican women with different HPV status.
2. Use “genome-centric” metagenomic analysis on the cervicovaginal microbiome of selected HPV+ and HPV-samples to reveal the genetic and functional make up of the most abundant microbial taxa, to help infer on their roles in HPV infections.
3. Characterize the estrogen metabolome for the HPV+ and HPV- urine samples through chromatography-mass spectroscopy (GC-MS) assays.
PI’s Technical Expertise: Microbial ecology, “Big data” analyses for massively parallel next generation sequences, metagenomics, microbial metabolic pathways and host-microbe interactions.
Interactions with the network of clinicians and scientists: Exploring the structure–function analyses of microbial elements in this infectious disease will be done in collaboration with the PI’s collaborator and mentor Dr. Martin Blaser, Director of the NYU Human Microbiome Program. Dr. Romaguera, an Ob/Gyn with extensive experience in HPV research, will acquire all the samples, and metabolomics experiments will be done with GC-MS approaches in collaboration with Dr. Natalyia Chorna (Director of the PR-INBRE Metabolomics Research Core).
The approaches that will be used include next-generation sequencing of 16S rDNA genes (V4), to reveal bacteria and archaeal diversity, and the Internal Transcribed Spacer region 1 for fungal characterization. Additionally, samples will be tested for Human papillomavirus through genotyping by type-specific PCR and sequencing. Selected metagenomic shotgun sequencing will explore gene abundance and possible microbiome relations to HPV infection, obesity and estradiol metabolism. Systemic estrogen metabolites will be characterized with Gas chromatography–mass spectrometry and linked to the microbiome and HPV profiles to test whether estrogen metabolites may be involved with functional activities of the cervicovaginal microbiome. The proposed project will provide invaluable training to mostly Hispanic undergraduate students at the Inter American University Metropolitan Campus, who will benefit from the research experiences including bioinformatics and data analyses training. The data produced through the project’s aims will be an essential prerequisite for comprehending the role of the cervicovaginal microbiota in HPV infections in Hispanics.
Additionally it will contribute to the discovery of improved treatments and ways to reduce the risk of acquiring HPV and ultimately cancer, while offering new alternatives for cervical probiotics, and finding new ways to predict and prevent an array of other diseases.