The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis

Study information

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

31749298

DOI Digital object identifier for electronic documents.

10.1111/1471-0528.15981

URI

Authors

Borgogna JC, Shardell MD, Santori EK, Nelson TM, Rath JM, Glover ED, Ravel J, Gravitt PE, Yeoman CJ, Brotman RM

Journal

BJOG : an international journal of obstetrics and gynaecology

Year

2020

Keywords:

16S rRNA gene amplicon sequencing, human papillomavirus, vaginal metabolome, vaginal microbiota

OBJECTIVE: Characterise the vaginal metabolome of cervical HPV-infected and uninfected women. DESIGN: Cross-sectional. SETTING: The Center for Health Behavior Research at the University of Maryland School of Public Health. SAMPLE: Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV+ ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV). METHOD: Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA. MAIN OUTCOME MEASURES: Metabolite abundances. RESULTS: Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV+ women had higher biogenic amine and phospholipid concentrations compared with HPV- women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV+ and HPV- women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV+ women than in HPV- women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV+ participants than in HPV- participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV). CONCLUSIONS: The vaginal metabolome of HPV+ women differed from HPV- women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention. TWEETABLE ABSTRACT: Metabolomics study: Vaginal microenvironment of HPV+ women may be informative for non-surgical interventions.

Experiment 1

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Vagina Distal oviductal region,Distal portion of oviduct,Vaginae,Vagina,vagina

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Human papilloma virus infection HPV,Human Papilloma Virus Infection,Human papilloma Virus infection,human papilloma virus infection,Human papillomavirus caused disease or disorder,Human papillomavirus disease or disorder,Human Papillomavirus Infection,Human Papillomavirus infection,Human papillomavirus infectious disease,Human papilloma virus infection

Group 0 name Corresponds to the control (unexposed) group for case-control studies: HPV-

Group 1 name Corresponds to the case (exposed) group for case-control studies: HPV+

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: HPV+ confirmed using Roche Linear Array HPV Genotyping Test

Group 0 sample size Number of subjects in the control (unexposed) group: 13

Group 1 sample size Number of subjects in the case (exposed) group: 26

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 30 days

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V3

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Signature 1

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: supplemental figure 3

Description: The association between vaginal taxa and detection status as identified by LEfSE

Abundance in Group 1: increased abundance in HPV+

NCBI	Quality Control	Links
Gardnerella vaginalis
Eggerthella
Gemella
Atopobium sp.
Veillonellaceae
Aerococcus christensenii
Peptoniphilus asaccharolyticus
Limosilactobacillus vaginalis