Nature Communications (Oct 2023)

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,
  • Samuel C. Forster

DOI
https://doi.org/10.1038/s41467-023-42112-w
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 11

Abstract

Read online

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.