Secretory immunoglobulin A (IgA) is an important component of the immune system that interacts with intestinal microbiota, promoting mucosal homeostasis. Although during inflammatory diseases, IgA-bacterial interactions are modified, the manner in which these connections are formed by the bacterial, host, and environmental factors is still unknown. The researchers employed IgA-SEQ to analyze fecal bacteria bound by IgA in 48 recurrent Clostridioides difficile patients prior to and post successful fecal microbiota transplantation (FMT) to get further knowledge. Escherichia coli was previously the most highly IgA-targeted species, but after FMT restored microbiota, other Firmicutes species were also, considered highly IgA-targeted. The route of FMT delivery (colonoscopy versus capsule) had no influence on post-FMT IgA targeting, suggesting that both methods result in the formation of healthy immune–bacterial interactions in the gut. Surprisingly, FMT recipients’ IgA-targeting was, very similar to that of the donors’, and fecal donor identity was strongly linked with recipient microbiota IgA targeting. The findings support the hypothesis that bacterial characteristics, rather than host genetics, influence IgA recognition among genetically distinct human hosts. The study suggested that human FMT recipients’ IgA-bacterial interactions are restored to resemble those of a healthy fecal donor, according to the conclusions.