Metabolic signature for a dysbiotic microbiome in the female genital tract: A systematic review and meta-analysis

Biban Gill; Ingrid Schwecht; Nuzhat Rahman; Tushar Dhawan; Chris Verschoor; Aisha Nazli; Charu Kaushic

doi:10.1111/aji.13781

Metabolic signature for a dysbiotic microbiome in the female genital tract: A systematic review and meta-analysis

Am J Reprod Immunol. 2023 Oct;90(4):e13781. doi: 10.1111/aji.13781.

Authors

Biban Gill^{1

2}, Ingrid Schwecht^{1

2}, Nuzhat Rahman^{1

2}, Tushar Dhawan^{1

2}, Chris Verschoor³, Aisha Nazli^{1

2}, Charu Kaushic^{1

2}

Affiliations

¹ Department of Medicine, McMaster University, Hamilton, ON, Canada.
² McMaster Immunology Research Center, Michael G. DeGroote Center for Learning and Discovery, McMaster University, Hamilton, ON, Canada.
³ Health Sciences North Research Institute, Northern Ontario School of Medicine, Sudbury, ON, Canada.

PMID: 37766408
DOI: 10.1111/aji.13781

Abstract

Background: The vaginal microbiome (VMB) is a critical determinant of reproductive health, where a microbial shift towards a dysbiotic environment has implications for susceptibility to, and clinical presentation of sexually transmitted infections (STIs). Metabolomic profiling of the vaginal microenvironment has led to the identification of metabolic responses to clinical conditions of dysbiosis. However, no studies have examined metabolic markers that are common across conditions and can serve as a signature for vaginal dysbiosis.

Method of study: We have conducted a comprehensive systematic review and meta-analysis to identify consistently deregulated metabolites along with their impact on host and microbial metabolism during dysbiosis. We employed two complementary approaches including a vote counting analysis for all eligible studies identified in the systematic review, in addition to a meta-analysis for a subset of studies with sufficient available data. Significantly deregulated metabolites were then selected for pathway enrichment analysis.

Results: Our results revealed a total of 502 altered metabolites reported across 10 dysbiotic conditions from 16 studies. Following a rigorous, collective analysis, six metabolites which were consistently downregulated and could be generalized to all dysbiotic conditions were identified. In addition, five downregulated and one upregulated metabolite was identified from a bacterial vaginosis (BV) focused sub-analysis. These metabolites have the potential to serve as a metabolic signature for vaginal dysbiosis. Their role in eight altered metabolic pathways indicates a disruption of amino acid, carbohydrate, and energy metabolism during dysbiosis.

Conclusion: Based on this analysis, we propose a schematic model outlining the common metabolic perturbations associated with vaginal dysbiosis, which can be potential targets for therapeutics and prophylaxis.

Keywords: dysbiosis4; female genital tract1; meta-analysis5; systematic review5; vaginal metabolome3; vaginal microbiome2.

Publication types

Review

Grants and funding

FRN#126019/CAPMC/ CIHR/Canada