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

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 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 Crohn’s 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.