DOP69 Glycans as an actor in the microbiome-immune response crosstalk

Abstract Background The perturbation of the symbiotic relationship between microbes and intestinal immune system contributes to Inflammatory Bowel Disease (IBD) development even years before diagnosis. However, causes underlying loss gut microbial equilibrium (dysbiosis) associated with inflammation still remain unknow. host glycocalyx (repertoire glycans/sugar-chains at surface mucosa) constitutes a major biological interface mucosa microorganisms1. In this study we aimed evaluate whether how an altered glycome perturbs microbiome composition dysbiosis initiation inflammation. Methods We have modulated glycosylation profile level using specific glycoengineered mouse models (KO) that exhibit alterations (deficiencies) in composition. Colitis was induced DSS analysis performed by 16S rDNA sequencing both WT KO mice. glyco-immunoprofile characterized. Results first demonstrated different mice changes glycans resulted characterized significant decrease beneficial members Firmicutes phylum compared These deficiency exhibited higher susceptibility colitis2. Then, determine causal effect glycosylation-induced microbiota modulation, co-housed After 5 weeks cohousing mice, much less severe colitis increased proportion bacteria from single housed Inferred metagenomics further revealed alteration biosynthetic pathway apparently shared gained upon co-housing WT. colonic inflammatory infiltrate cohoused showed expression IL17 IL22 production mucosa, baseline DSS. This pinpoints potential protective enhancement biosynthesis (through sharing WT) for preventing dysregulation response. Conclusion study, demonstrate is colitis. results illustrate relevance shaping microbiota, highlighting its role maintaining homeostatic crosstalk immunity. funded ECCO Pioneer Award. 1. Verhelst, Gastroenterology 2020. PMID: 31626754 2. Dias et al PNAS 2018 29720442