DataSheet1_Increase of intestinal bacterial sialidase activity exacerbates acute colitis in mice.PDF

The availability of endogenous and dietary carbohydrates in the gastrointestinal tract influences the composition of the gut microbiota. Carbohydrate foraging requires the action of bacterially-encoded glycoside hydrolases, which release mono- and oligosaccharides taken up as carbon sources by multiple microbial taxa. In addition to providing nutrients to the microbiota, the cleavage of host glycans by bacterial glycoside hydrolases may alter the properties of surface glycoproteins involved in cell adhesion and activation processes in the gut lumen. To investigate the impact of bacterial glycoside hydrolase activities on the gut microbial composition and on host glycans during colon inflammation, we increased local glycoside hydrolase activity by supplementing mice with recombinant E. coli expressing specific sialidase, fucosidase and rhamnosidase enzymes during acute colitis induced by dextran sulfate sodium ingestion. Whereas increased fucosidase and rhamnosidase activity did not alter the course of colitis, increased sialidase activity exacerbated disease severity. The effect of increased sialidase activity on inflammation was not caused by changes in the microbial composition given that a similar shift in gut bacteria occurred in all groups of mice supplemented with recombinant E. coli. Increased sialidase activity in the colon of treated mice however significantly altered the distribution of sialic acid on mucosal glycans. Treatment of lamina propria dendritic cells with bacterial sialidase also strongly decreased the density of sialylated ligands to anti-inflammatory siglec lectins, indicating that the remodeling of surface sialylation caused by increased sialidase activity likely accounts for the observed exacerbation of acute colitis in mice.

胃肠道内源性和膳食碳水化合物的存在影响着肠道微生物群的组成。碳水化合物的觅食活动需要细菌编码的糖苷水解酶的作用，这些酶释放出单糖和寡糖，并被多种微生物类群作为碳源摄取。除了为微生物群提供营养外，细菌糖苷水解酶对宿主糖蛋白的裂解可能改变其参与肠道腔内细胞粘附和活化过程的特性。为了研究细菌糖苷水解酶活性对肠道微生物组成及宿主糖蛋白在结肠炎期间的影响，我们在由硫酸钠诱导的急性结肠炎小鼠模型中，通过补充表达特定唾液酸酶、岩藻糖酶和鼠李糖酶的重组大肠杆菌，提高了局部的糖苷水解酶活性。然而，尽管岩藻糖酶和鼠李糖酶活性的增加并未改变结肠炎的病程，唾液酸酶活性的增加却加剧了疾病的严重程度。由于在所有补充重组大肠杆菌的小鼠组中均观察到类似的肠道细菌变化，因此增加的唾液酸酶活性对炎症的影响并非由微生物组成的变化引起。然而，治疗小鼠结肠中唾液酸酶活性的增加显著改变了粘膜糖蛋白上唾液酸的分部。用细菌唾液酸酶处理固有层树突状细胞也显著降低了抗炎siglec凝集素的唾液酰化配体的密度，这表明由唾液酸酶活性增加引起的表面唾液化重塑可能是小鼠急性结肠炎加剧观察到的原因。