TY - JOUR
T1 - Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota
AU - Kashyap, Purna C.
AU - Marcobal, Angela
AU - Ursell, Luke K.
AU - Smits, Samuel A.
AU - Sonnenburg, Erica D.
AU - Costello, Elizabeth K.
AU - Higginbottom, Steven K.
AU - Domino, Steven E.
AU - Holmes, Susan P.
AU - Relman, David A.
AU - Knight, Rob
AU - Gordon, Jeffrey I.
AU - Sonnenburg, Justin L.
PY - 2013/10/15
Y1 - 2013/10/15
N2 - 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 dietdependent manner.
AB - 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 dietdependent manner.
KW - Host-microbial mutualism
KW - Intestinal microbiota
KW - Metabolomics
UR - http://www.scopus.com/inward/record.url?scp=84885711264&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885711264&partnerID=8YFLogxK
U2 - 10.1073/pnas.1306070110
DO - 10.1073/pnas.1306070110
M3 - Article
C2 - 24062455
AN - SCOPUS:84885711264
SN - 0027-8424
VL - 110
SP - 17059
EP - 17064
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 42
ER -