Abstract Bacterial vaginosis (BV) is the most prevalent vaginal condition among reproductive-age women presenting with vaginal complaints. Despite its significant impact on women’s health, limited knowledge exists regarding the microbial community composition and metabolic interactions associated with BV. In this study, we analyze metagenomic data obtained from human vaginal swabs to generate in silico predictions of BV-associated bacterial metabolic interactions via genome-scale metabolic network reconstructions (GENREs). While most efforts to characterize symptomatic BV (and thus guide therapeutic intervention by identifying responders and non-responders to treatment) are based on genomic profiling, our in silico simulations reveal functional metabolic relatedness between species as quite distinct from genetic relatedness. We grow several of the most common co-occurring bacteria (Prevotella amnii, Prevotella buccalis, Hoylesella timonensis, Lactobacillus iners, Fannyhessea vaginae, andAerrococcus christenssii) on the spent media ofGardnerellaspecies and perform metabolomics to identify potential mechanisms of metabolic interaction. Through these analyses, we identify BV-associated bacteria that produce caffeate, a compound implicated in estrogen receptor binding, when grown in the spent media of other BV-associated bacteria. These findings underscore the complex and diverse nature of BV-associated bacterial community structures and several of these mechanisms are of potential significance in understanding host-microbiome relationships.
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Model-based and phylogenetically adjusted quantification of metabolic interaction between microbial species
Microbial community members exhibit various forms of interactions. Taking advantage of the increasing availability of microbiome data, many computational approaches have been developed to infer bacterial interactions from the co-occurrence of microbes across diverse microbial communities. Additionally, the introduction of genome-scale metabolic models have also enabled the inference of cooperative and competitive metabolic interactions between bacterial species. By nature, phylogenetically similar microbial species are more likely to share common functional profiles or biological pathways due to their genomic similarity. Without properly factoring out the phylogenetic relationship, any estimation of the competition and cooperation between species based on functional/pathway profiles may bias downstream applications. To address these challenges, we developed a novel approach for estimating the competition and complementarity indices for a pair of microbial species, adjusted by their phylogenetic distance. An automated pipeline, PhyloMint, was implemented to construct competition and complementarity indices from genome scale metabolic models derived from microbial genomes. Application of our pipeline to 2,815 human-gut associated bacteria showed high correlation between phylogenetic distance and metabolic competition/cooperation indices among bacteria. Using a discretization approach, we were able to detect pairs of bacterial species with cooperation scores significantly higher than the average pairs of bacterial species with similar phylogenetic distances. A network community analysis of high metabolic cooperation but low competition reveals distinct modules of bacterial interactions. Our results suggest that niche differentiation plays a dominant role in microbial interactions, while habitat filtering also plays a role among certain clades of bacterial species.
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- Award ID(s):
- 2025451
- PAR ID:
- 10297357
- Editor(s):
- Ouzounis, Christos A.
- Date Published:
- Journal Name:
- PLOS Computational Biology
- Volume:
- 16
- Issue:
- 10
- ISSN:
- 1553-7358
- Page Range / eLocation ID:
- e1007951
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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