Abstract
Immunoglobulin A (IgA) is the most abundant antibody within the mammalian gut, where it binds to both pathogenic and commensal microbes. Despite its prevalence, the impact of IgA upon the biology and behavior of individual microbes remains poorly understood. Here we present Paired Immunoglobulin Sequencing (PIg-seq), a high-throughput method to identify IgA-associated changes in bacterial gene expression. Using PIg-seq we uncover widespread, and in many cases previously unrecognized, transcriptional responses associated with IgA-binding within the mouse gut. While many of these associations are conserved across diverse bacterial lineages, others vary dramatically even between closely related strains, revealing striking strain-level heterogeneity. Most notably, IgA binding is associated with altered expression of bacterial conjugation genes, and multiple prophages, suggesting an exciting link between adaptive immunity and horizontal gene transfer. Together, our findings establish IgA as a key regulator of microbial behavior, with potential consequences for both the ecology and the evolution of the gut microbiome.