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

聚糖代谢是影响肠道微生物群组成和生理的重要因素，胃肠道糖基化谱的变化通常由血型相关糖基转移酶介导。已知这类基因会影响共生菌和致病菌，因此显示出种群间病原体驱动选择的明确特征。该提案将通过研究小鼠和人类之间保守的两种血型相关糖基转移酶，即B4galnt2和Fut2，重点关注宿主糖基化，肠道微生物群和对GI病原体和炎症的易感性之间的相互作用。将使用病原体肠道沙门氏菌血清型鼠伤寒和啮齿类柠檬酸杆菌以及葡聚糖硫酸钠（DSS）诱导的结肠炎模型研究它们在肠道炎症发展中的作用。为了将宿主糖基化和炎症反应的变化与肠道微生物群的变化联系起来，将在16S rRNA基因和鸟枪宏基因组测序水平上进行微生物生态分析。总之，这些实验将阐明微生物群落，宿主糖基化或其相互作用的变化在多大程度上有助于对肠道细菌病原体和炎症的易感性差异。

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.