Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota

Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17059-64. doi: 10.1073/pnas.1306070110. Epub 2013 Sep 23.

Abstract

We investigate how host mucus glycan composition interacts with dietary carbohydrate content to influence the composition and expressed functions of a human gut community. The humanized gnotobiotic mice mimic humans with a nonsecretor phenotype due to knockout of their α1-2 fucosyltransferase (Fut2) gene. The fecal microbiota of Fut2(-) mice that lack fucosylated host glycans show decreased alpha diversity relative to Fut2(+) mice and exhibit significant differences in community composition. A glucose-rich plant polysaccharide-deficient (PD) diet exerted a strong effect on the microbiota membership but eliminated the effect of Fut2 genotype. Additionally fecal metabolites predicted host genotype in mice on a polysaccharide-rich standard diet but not on a PD diet. A more detailed mechanistic analysis of these interactions involved colonization of gnotobiotic Fut2(+) and Fut2(-) mice with Bacteroides thetaiotaomicron, a prominent member of the human gut microbiota known to adaptively forage host mucosal glycans when dietary polysaccharides are absent. Within Fut2(-) mice, the B. thetaiotaomicron fucose catabolic pathway was markedly down-regulated, whereas BT4241-4247, an operon responsive to terminal β-galactose, the precursor that accumulates in the Fut2(-) mice, was significantly up-regulated. These changes in B. thetaiotaomicron gene expression were only evident in mice fed a PD diet, wherein B. thetaiotaomicron relies on host mucus consumption. Furthermore, up-regulation of the BT4241-4247 operon was also seen in humanized Fut2(-) mice. Together, these data demonstrate that differences in host genotype that affect the carbohydrate landscape of the distal gut interact with diet to alter the composition and function of resident microbes in a diet-dependent manner.

Keywords: host–microbial mutualism; intestinal microbiota; metabolomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteroides / genetics
  • Bacteroides / metabolism*
  • Dietary Carbohydrates / pharmacology*
  • Fucosyltransferases* / genetics
  • Fucosyltransferases* / metabolism
  • Glucans* / genetics
  • Glucans* / metabolism
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology*
  • Mice
  • Mice, Knockout
  • Microbiota / physiology*

Substances

  • Dietary Carbohydrates
  • Glucans
  • Fucosyltransferases
  • galactoside 2-alpha-L-fucosyltransferase

Associated data

  • GEO/GSE45641