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

100 Citations (Scopus)

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

Fingerprint

Crohn disease
Crohn Disease
energy metabolism
Energy Metabolism
polymorphism
digestive system
metabolism
genetic polymorphism
intestinal mucosa
Microbiota
vitamin metabolism
biosynthesis
antigens
energy
metabolome
Intestinal Mucosa
antigen
genotype
body fluids
metabolomics

Keywords

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

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Tong, M., Mchardy, I. H., Ruegger, P., Goudarzi, M., Kashyap, P. C., Haritunians, T., ... 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

Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism. / Tong, Maomeng; Mchardy, Ian Howard; 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 P B; Borneman, James; Braun, Jonathan.

In: ISME Journal, Vol. 8, No. 11, 25.11.2014, p. 2193-2206.

Research output: Contribution to journalArticle

Tong, M, Mchardy, IH, Ruegger, P, Goudarzi, M, Kashyap, PC, Haritunians, T, Li, X, Graeber, TG, Schwager, E, Huttenhower, C, Fornace, AJ, Sonnenburg, JL, McGovern, DPB, Borneman, J & Braun, J 2014, 'Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism', ISME Journal, vol. 8, no. 11, pp. 2193-2206. https://doi.org/10.1038/ismej.2014.64
Tong, Maomeng ; Mchardy, Ian Howard ; 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 P B ; Borneman, James ; Braun, Jonathan. / Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism. In: ISME Journal. 2014 ; Vol. 8, No. 11. pp. 2193-2206.
@article{f0ce1e40415c42669b15610276b5a344,
title = "Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism",
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.",
keywords = "glycan foraging, intestinal microbiome, microbial ecology, multi'omic analysis",
author = "Maomeng Tong and Mchardy, {Ian Howard} and Paul Ruegger and Maryam Goudarzi and Kashyap, {Purna C.} and Talin Haritunians and Xiaoxiao Li and Graeber, {Thomas G.} and Emma Schwager and Curtis Huttenhower and Fornace, {Albert J.} and Sonnenburg, {Justin L.} and McGovern, {Dermot P B} and James Borneman and Jonathan Braun",
year = "2014",
month = "11",
day = "25",
doi = "10.1038/ismej.2014.64",
language = "English (US)",
volume = "8",
pages = "2193--2206",
journal = "ISME Journal",
issn = "1751-7362",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism

AU - Tong, Maomeng

AU - Mchardy, Ian Howard

AU - Ruegger, Paul

AU - Goudarzi, Maryam

AU - Kashyap, Purna C.

AU - Haritunians, Talin

AU - Li, Xiaoxiao

AU - Graeber, Thomas G.

AU - Schwager, Emma

AU - Huttenhower, Curtis

AU - Fornace, Albert J.

AU - Sonnenburg, Justin L.

AU - McGovern, Dermot P B

AU - Borneman, James

AU - Braun, Jonathan

PY - 2014/11/25

Y1 - 2014/11/25

N2 - 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.

AB - 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.

KW - glycan foraging

KW - intestinal microbiome

KW - microbial ecology

KW - multi'omic analysis

UR - http://www.scopus.com/inward/record.url?scp=84908234204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908234204&partnerID=8YFLogxK

U2 - 10.1038/ismej.2014.64

DO - 10.1038/ismej.2014.64

M3 - Article

C2 - 24781901

AN - SCOPUS:84908234204

VL - 8

SP - 2193

EP - 2206

JO - ISME Journal

JF - ISME Journal

SN - 1751-7362

IS - 11

ER -