Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota.
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.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
Purna C
PC
Kashyap
Angela
A
Marcobal
Luke K
LK
Ursell
Samuel A
SA
Smits
Erica D
ED
Sonnenburg
Elizabeth K
EK
Costello
Steven K
SK
Higginbottom
Steven E
SE
Domino
Susan P
SP
Holmes
David A
DA
Relman
Rob
R
Knight
Jeffrey I
JI
Gordon
Justin L
JL
Sonnenburg
D000818:Animals; D001439:Bacteroides / Q000235:genetics / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D005936:Glucans / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000502:physiology*; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D004040:Dietary Carbohydrates; D005647:Fucosyltransferases; D005936:Glucans; D000097631:Galactoside 2-alpha-L-fucosyltransferase
host–microbial mutualism; intestinal microbiota; metabolomics