Metagenomic immunoglobulin sequencing reveals IgA coating of microbial strains in the healthy human gut

IgA, the primary human antibody secreted from the gut mucosa, shapes the intestinal microbiota. Methodological limitations have hindered defining which microbial strains are targeted by IgA and the implications of binding. Here we develop a technique, metagenomic immunoglobulin sequencing (MIg-seq), that provides strain-level resolution of microbes coated by IgA and use it to determine IgA coating levels for 3,520 gut microbiome strains in healthy human faeces. We find that both health and disease-associated bacteria are targeted by IgA. Microbial genes are highly predictive of IgA binding levels; in particular, mucus degradation genes are correlated with high binding, and replication rates are significantly reduced for microbes bound by IgA. We demonstrate that IgA binding is more correlated with host immune status than traditional relative abundance measures of microbial community composition. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host-microbe interactions.