Gut IgA abundance in adult life can protect from DSS colitis even if maternal IgA received in early life is inadequate

Susceptibility to DSS induced colitis has been shown to depend on various host and microbial factors, the caveat being that most of these studies have used gene-deficient or gnotobiotic mouse models. In order to study specific factors contributing to colitis susceptibility under more physiological conditions we used inbred mouse strains that differ in their IgA responses but are otherwise healthy. We found that the IgA high strain CBA/CaJ (CBA) is resistant to DSS-colitis unlike the IgA low strain C57BL/6 (B6) strain and resistance correlated with extensive IgA-coating of fecal bacteria and lower fecal bacterial loads. Additionally, we found a more robust intestinal barrier in CBA mouse, along with lower intestinal inflammation and bacterial translocation during colitis induction. Through homologous fecal microbial transplants we found that the IgA-uncoated fraction of B6 flora was relatively more colitogenic. Further, experiments with F1 and F1xParent ‘backcrossed’ progeny generated separately with CBA and B6 dams indicated that pups born to IgA high proximal dams were resistant to colitis. These results indicate a role of passive maternal IgA and active IgA in colitis resistance. In order to understand whether early exposure to passive IgA alone can confer resistance to colitis, we foster-nursed B6 pups on CBA dams and vice-versa but it did not have an effect on DSS susceptibility. Interestingly, oral administration of immunoglobulins to B6 adults did decrease DSS associated disease. Collectively, our data indicate that higher gut IgA in adult life plays a more important role as compared to maternal IgA received during early life in conferring resistance to DSS colitis.