Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn’s disease

Patients with Crohn’s disease (CD) exhibit great heterogeneity in disease presentation and treatment responses, where distinct gut microbiota-host interplays may play part in the yet unresolved disease etiology. We here characterized absolute and relative single and multi-coating of gut bacteria with immunoglobulin (Ig)A, IgG1, IgG2, IgG3 and IgG4 in CD patients and healthy controls. Patients with severe disease exhibited distinctly higher gut bacterial IgG2-coating. IgG2-coated bacteria included both known pathogenic and non-pathogenic bacteria that co-existed in communities with two non-coated gut pathobionts Campylobacter and Mannheimia . These latter two exhibited low prevalence, rarely coincided, and were strongly enriched during disease flares in CD patients across independent and geographically distant cohorts. Since antibody-coating of gut pathobionts diminishes epithelial invasion and inflammatory processes, escape from coating by specific gut pathobionts may be a mechanism related to disease flares in the subgroup of CD patients with severe disease.