Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism
In: The ISME Journal: Multidisciplinary Journal of Microbial Ecology, vol 8, iss 11, 2014
academicJournal
Zugriff:
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.
Titel: |
Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism
|
---|---|
Autor/in / Beteiligte Person: | Tong, Maomeng ; McHardy, Ian ; Ruegger, Paul ; Goudarzi, Maryam ; Kashyap, Purna C ; Haritunians, Talin ; Li, Xiaoxiao ; Graeber, Thomas G ; Schwager, Emma ; Huttenhower, Curtis ; Fornace, Albert J ; Sonnenburg, Justin L ; McGovern, Dermot PB ; Borneman, James ; Braun, Jonathan |
Link: | |
Zeitschrift: | The ISME Journal: Multidisciplinary Journal of Microbial Ecology, vol 8, iss 11, 2014 |
Veröffentlichung: | eScholarship, University of California, 2014 |
Medientyp: | academicJournal |
Schlagwort: |
|
Sonstiges: |
|