Secretory IgA–Gut Microbiota Crosstalk in Mucosal Immunity

Secretory immunoglobulin A (SIgA) represents the most abundant antibody isotype at mucosal surfaces and plays a central role in maintaining intestinal immune homeostasis. In addition to its classical function in immune exclusion of pathogens, SIgA actively shapes the composition, spatial organization, and functional behavior of the gut microbiota, thereby contributing to a dynamic and reciprocal host–microbe relationship. Increasing evidence highlights that crosstalk between SIgA and the gut microbiota is not merely protective but also regulatory, influencing immune tolerance, barrier integrity, and inflammatory balance within the intestinal mucosa. This review provides a comprehensive overview of the molecular and immunological mechanisms underlying SIgA–microbiota interactions in mucosal immunity. We discuss the processes governing SIgA induction, class switching, and antigen specificity, as well as the mechanisms by which SIgA selectively coats commensal and pathogenic microorganisms. Emphasis is placed on how SIgA-mediated immune modulation shapes microbial ecology, limits immune overactivation, and maintains long-term mucosal homeostasis. Moreover, the review describes the role of dysregulation in SIgA–microbiota interactions in immune-mediated and inflammatory diseases, as well as the emerging translational perspectives. This includes the potential of SIgA-targeted strategies to modulate the gut microbiota for therapeutic benefit. By integrating mechanistic insights with clinical relevance, this review highlights SIgA–microbiota interactions at the intersection of mucosal immunology and emerging immunotherapeutic opportunities.