Kashyap_fut2_16S

A key factor that influences microbiota composition and function is the identity and quantity of carbohydrates in the distal gut. Both dietary and host-derived (e.g., mucosal) glycans are known to play important nutritional roles for members of the microbiota, but relatively little is known about how these two sources of carbohydrates interact in vivo to influence the microbiota. Here we have investigated how genetically-dictated alterations in host mucus carbohydrate composition interacts with diet to influence resident microbiota function and composition. We have used germ free (GF) ??1-2 fucosyltransferase (FUT2) knock out mice (Fuc-), which lack fucose residues on host-derived intestinal glycans, to serve as a model of human non-secretors that lack a functional copy of Fut2 and are at increased risk for developing Crohn???s disease. The fecal microbiota of Fuc- mice colonized with a human fecal microbiota (???humanized???) show decreased alpha diversity relative to Fuc+ mice, as well as significant differences in community composition. A polysaccharide deficient (PD) diet eliminated the FUC genotype effect and exerted a strong effect on the microbiota membership compared to a standard chow diet. The host urinary and fecal metabolite profile under these conditions mirrored changes in microbial composition. Transcriptional profiling of the model symbiont Bacteroides thetaiotaomicron in vivo in mono-associated adult Fuc- mice and Fuc+ mice fed a PD diet revealed a host genotype-specific impact on microbe functionality related to utilization of fucosylated glycans. These data demonstrate that differences in host genotype that affect the carbohydrate landscape of the distal gut can alter the composition and function of the resident microbes in a diet-dependent manner.