Disease-specific loss of microbial cross-feeding interactions in the human gut

Vanessa R. Marcelino (), Caitlin Welsh, Christian Diener, Emily L. Gulliver, Emily L. Rutten, Remy B. Young, Edward M. Giles, Sean M. Gibbons, Chris Greening and Samuel C. Forster ()
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Vanessa R. Marcelino: Monash University
Caitlin Welsh: Biomedicine Discovery Institute
Christian Diener: Institute for Systems Biology
Emily L. Gulliver: Monash University
Emily L. Rutten: Monash University
Remy B. Young: Monash University
Edward M. Giles: Hudson Institute of Medical Research
Sean M. Gibbons: Institute for Systems Biology
Chris Greening: Biomedicine Discovery Institute
Samuel C. Forster: Monash University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases. When applied to a Crohn’s disease case-control study, our approach identifies a lack of species with the ability to consume hydrogen sulfide as the main distinguishing microbiome feature of disease. We propose that our conceptual framework will help prioritize in-depth analyses, experiments and clinical targets, and that targeting the restoration of microbial cross-feeding interactions is a promising mechanism-informed strategy to reconstruct a healthy gut ecosystem.

Date: 2023
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DOI: 10.1038/s41467-023-42112-w

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