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

lunes, 21 de octubre de 2013

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

Edited by Ralph R. Isberg, Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, MA, and approved August 21, 2013 (received for review March 29, 2013)

Significance

Our 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.

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.

host–microbial mutualism

intestinal microbiota

metabolomics

Footnotes

¹To whom correspondence should be addressed. E-mail: jsonnenburg@stanford.edu.

Author contributions: P.C.K., A.M., L.K.U., S.A.S., E.D.S., S.K.H., S.P.H., J.I.G., and J.L.S. designed research; P.C.K., A.M., L.K.U., S.A.S., E.D.S., S.K.H., S.P.H., and J.L.S. performed research; L.K.U., S.A.S., E.K.C., S.E.D., S.P.H., D.A.R., R.K., and J.I.G. contributed new reagents/analytic tools; P.C.K., A.M., L.K.U., S.A.S., S.P.H., R.K., and J.L.S. analyzed data; and P.C.K., S.A.S., J.I.G., and J.L.S. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The GeneChip datasets have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE45641). The 16S sequence data have been deposited in the European Molecular Biology Laboratory (EMBL) nucleotide archive (accession no. ERP003630), and can also be found in the Quantitative Insights into Microbial Ecology (QIIME) database, www.microbio.me/qiime (study ID 1452).