Stratification of human gut microbiomes by succinotype is associated with inflammatory bowel disease status

Abstract

The human gut microbiome produces and consumes a variety of compounds that interact with the host and impact health. Succinate is of particular interest as it intersects with both host and microbiome metabolism. However, which gut bacteria are most responsible for the consumption of intestinal succinate is poorly understood. Here, we build upon an enrichment-based whole fecal sample culturing approach and identify two main bacterial taxa that are responsible for succinate consumption in the human intestinal microbiome,PhascolarctobacteriumandDialister. These two taxa have the hallmark of a functional guild and are strongly mutual exclusive across over 20,000 fecal samples in nearly 100 cohorts and can thus be used to assign a robust ‘succinotype’ to an individual. We show that they differ with respect to their rate of succinate consumptionin vitroand that this is associated with higher concentrations of fecal succinate. Finally, individuals suffering from inflammatory bowel disease (IBD) are more likely to have theDialistersuccinotype compared to healthy subjects. The functionally meaningful classification of human intestinal microbiota based on ‘succinotype’ thus builds a bridge between microbiome function and IBD pathophysiology related to succinate.