Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism

Maomeng Tong, Ian Howard Mchardy, Paul Ruegger, Maryam Goudarzi, Purna C. Kashyap, Talin Haritunians, Xiaoxiao Li, Thomas G. Graeber, Emma Schwager, Curtis Huttenhower, Albert J. Fornace, Justin L. Sonnenburg, Dermot P B McGovern, James Borneman, Jonathan Braun

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Fucosyltransferase 2 (FUT2) is an enzyme that is responsible for the synthesis of the H antigen in body fluids and on the intestinal mucosa. The H antigen is an oligosaccharide moiety that acts as both an attachment site and carbon source for intestinal bacteria. Non-secretors, who are homozygous for the loss-of-function alleles of FUT2 gene (sese), have increased susceptibility to Crohn's disease (CD). To characterize the effect of FUT2 polymorphism on the mucosal ecosystem, we profiled the microbiome, meta-proteome and meta-metabolome of 75 endoscopic lavage samples from the cecum and sigmoid of 39 healthy subjects (12 SeSe, 18 Sese and 9 sese). Imputed metagenomic analysis revealed perturbations of energy metabolism in the microbiome of non-secretor and heterozygote individuals, notably the enrichment of carbohydrate and lipid metabolism, cofactor and vitamin metabolism and glycan biosynthesis and metabolism-related pathways, and the depletion of amino-acid biosynthesis and metabolism. Similar changes were observed in mice bearing the FUT2 -/- genotype. Metabolomic analysis of human specimens revealed concordant as well as novel changes in the levels of several metabolites. Human metaproteomic analysis indicated that these functional changes were accompanied by sub-clinical levels of inflammation in the local intestinal mucosa. Therefore, the colonic microbiota of non-secretors is altered at both the compositional and functional levels, affecting the host mucosal state and potentially explaining the association of FUT2 genotype and CD susceptibility.

Original languageEnglish (US)
Pages (from-to)2193-2206
Number of pages14
JournalISME Journal
Volume8
Issue number11
DOIs
StatePublished - Nov 25 2014

Keywords

  • glycan foraging
  • intestinal microbiome
  • microbial ecology
  • multi'omic analysis

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics

Fingerprint Dive into the research topics of 'Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism'. Together they form a unique fingerprint.

  • Cite this

    Tong, M., Mchardy, I. H., Ruegger, P., Goudarzi, M., Kashyap, P. C., Haritunians, T., Li, X., Graeber, T. G., Schwager, E., Huttenhower, C., Fornace, A. J., Sonnenburg, J. L., McGovern, D. P. B., Borneman, J., & Braun, J. (2014). Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism. ISME Journal, 8(11), 2193-2206. https://doi.org/10.1038/ismej.2014.64