Characterizing the interaction between blood group-related glycosyltransferases and the intestinal microbiota using multi-omic approaches

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Glycan metabolism is an important factor contributing to the composition and physiology of the intestinal microbiota, and variation in the glycosylation profile of the GI tract is often mediated by blood group-related glycosyltransferases. This class of genes is known to influence both symbiotic and pathogenic bacteria, and accordingly displays clear signatures of pathogen-driven selection among populations. This proposal will focus on the interplay between host glycosylation, the intestinal microbiota and susceptibility to GI pathogens and inflammation by investigating two blood group-related glycosyltransferases that are conserved between mice and humans, namely B4galnt2 and Fut2. Their role in the development of intestinal inflammation will be investigated using the pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium, as well as a dextran sodium sulfate (DSS)-induced colitis model. To relate changes in host glycosylation and inflammatory response to changes in the intestinal microbiota, microbial ecological analyses will be performed at the level of 16S rRNA gene- and shotgun metagenomic sequencing. Together, these experiments will elucidate to what degree changes in microbial communities, host glycosylation or their interaction contribute to differences in susceptibility to enteric bacterial pathogens and inflammation.