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

Rossetto Marcelino, V.; Welsh, C.; Diener, C.; Gulliver, E. L.; Rutten, E. L.; Young, R. B.; Giles, E. M.; Gibbons, S. M.; Greening, C.; Forster, S. C.

doi:10.1101/2023.02.17.528570

bioRxiv · 10.1101/2023.02.17.528570

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

Rossetto Marcelino, V.·Welsh, C.·Diener, C.·Gulliver, E. L.·Rutten, E. L.·Young, R. B.·Giles, E. M.·Gibbons, S. M.·Greening, C.·Forster, S. C.

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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 metagenome-wide metabolic models from over 1600 individuals, the MES allowed us to identify and rank metabolic interactions that were significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases. When applied to a Crohns disease case-control study, our approach identified a lack of species with the ability to consume hydrogen sulphide 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.

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Rossetto Marcelino, V., Welsh, C., Diener, C., Gulliver, E. L., Rutten, E. L., Young, R. B., Giles, E. M., Gibbons, S. M., Greening, C., Forster, S. C.. 2023-02-17. Disease-specific loss of microbial cross-feeding interactions in the human gut. https://doi.org/10.1101/2023.02.17.528570

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