Paired sequencing of IgA-bound bacteria reveals widespread associations between adaptive immunity and gut microbiome gene expression.

Immunoglobulin A (IgA) is the most abundant antibody in the mammalian gut, where it binds both pathogenic and commensal microbes. Despite its prevalence, the impact of IgA on the biology and behavior of individual microbes has remained poorly understood.

To address this, the authors developed Paired Immunoglobulin Sequencing (PIg-seq), a high-throughput method to identify IgA-associated changes in bacterial gene expression, and applied it to the mouse gut.

Using PIg-seq, they uncovered widespread and in many cases previously unrecognized transcriptional responses associated with IgA binding. Many of these associations were conserved across diverse bacterial lineages, while others varied dramatically even between closely related strains, revealing striking strain-level heterogeneity. Most notably, IgA binding was associated with altered expression of bacterial conjugation genes and multiple prophages.

Together, the findings establish IgA as a key regulator of microbial behavior, with potential consequences for both the ecology and evolution of the gut microbiome, and suggest a link between adaptive immunity and horizontal gene transfer.