Tong, MaomengMcHardy, IanRuegger, PaulGoudarzi, MaryamKashyap, Purna CHaritunians, TalinLi, XiaoxiaoGraeber, Thomas GSchwager, Emma HoldrichHuttenhower, CurtisFornace, Albert JSonnenburg, Justin LMcGovern, Dermot PBBorneman, JamesBraun, Jonathan2016-11-182014Tong, M., I. McHardy, P. Ruegger, M. Goudarzi, P. C. Kashyap, T. Haritunians, X. Li, et al. 2014. “Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism.” The ISME Journal 8 (11): 2193-2206. doi:10.1038/ismej.2014.64. http://dx.doi.org/10.1038/ismej.2014.64.1751-7362http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407857Fucosyltransferase 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.en-USglycan foragingintestinal microbiomemicrobial ecologymulti'omic analysisJournal Article2016-11-1810.1038/ismej.2014.64