IgA Determines Bacterial Composition in the Gut

BACKGROUND: Classically, IgA in the gut prevents the invasion of microorganisms to systemic organs through the process of neutralization and immune exclusion. Interestingly, recent reports suggest that IgA might help in biofilm formation and promote bacterial growth inside the intestine. METHODS: In this study, we used flow cytometry, ELISA, and chemical models of colitis to test whether the quality and quantity of IgA can select for bacterial persistence in the gut. RESULTS: We found that members of Proteobacteria, such as γ-Proteobacteria and SFB, are preferentially coated by IgA in WT mice. In the partial absence of either T-dependent or -independent IgA responses, there are no significant differences in the frequency of bacteria coated with IgA in mice. However, Rag−/− mice that lack all antibodies had a severe reduction in Proteobacteria and were resistant to DSS-induced colitis, suggesting that secretory IgA might be essential for differential retention of these taxa in the mouse gut. Rag−/− littermates in the F2 generation generated from (B6 × Rag−/−) F1 mice acquired the underrepresented bacteria taxa such as γ-Proteobacteria through vertical transmission of flora. They died soon after weaning, possibly due to the acquired flora. Additionally, continued exposure of Rag−/− mice to B6 flora by cohousing mice led to the acquisition of γ-Proteobacteria and mortality. CONCLUSIONS: Together, our results indicate that host survival in the complete absence of an IgA response necessitates the exclusion of specific bacterial taxa from the gut microbiome.