Alteration of microbiota antibody-mediated immune selection contributes to dysbiosis in Inflammatory Bowel Diseases

Secretory immunoglobulin A (SIgA) select gut commensals via glycan-glycan interactions and dynamic transport to and from the mucosa, but SIgA1 and SIgA2 behavior remain largely unknown during Inflammatory Bowel Diseases (IBD).  We show that Crohn’s disease (CD) IgA1 gains retro-transport ability and selects a distinct microbiota while Ulcerative colitis (UC) IgA2 loses its natural retro-transport function and reactivity. Additionally, CD IgAs have increased anti-glycan reactivity while UC IgA presents significant loss in anti-glycan reactivity. Finally, local IgA2 selection of the microbiota in active CD differs from that of inactive CD. suggesting IgA2 may have more of a pathogenic tissular role in CD while IgA1 has a pathogenic luminal role. This is the first study dedicated to the specific focus on the impact of IgA subclasses and structure on their interaction with the microbiota in IBD. It suggests that repertoires of IgA⁺ microbiota could be predictive of active disease in CD and that analysis of IgA-specific glycosylations could be important biomarkers for IBD diagnosis and outcome prediction. In addition, characterization of IgA+-microbiota fraction could be an important predictive parameters for fecal microbiota transplantation efficacy given its diverse outcome in both CD and UC.