Antibody-mediated immune surveillance as an organizing axis of gut microbiota structure

Abstract Background The symbiotic interplay between the immune system and the endogenous microbiome is essential for maintaining homeostasis. However, most microbiome research focuses primarily on associations between disease and microbial composition, often overlooking host–microbiota interactions as a defining component of health and pathology. The gut microbiota is continuously monitored by the immune system, particularly via immunoglobulin A (IgA), which shapes microbial communities by selectively targeting specific taxa. Despite its central role, IgA-mediated immune surveillance has rarely been formalized as a quantitative axis in microbiota analysis, limiting our understanding of how host–microbe interactions influence health and disease. Results We developed an immune-informed framework to quantify IgA-mediated microbial engagement using the Species Immune Engagement Score (IM score ). IM score integrates three key features: IgA binding to each microbe, microbial abundance, and prevalence across individuals, producing a quantitative measure of how actively the immune system targets each taxon. Applying IM score across three geographically distinct cohorts, we identified a conserved set of IgA-targeted gut microbes. This includes well-characterized commensals, such as Coprococcus comes and uncharacterized taxa (e.g . , Oscillospiraceae SGB15216), highlighting microbes that are immunologically relevant but often overlooked. In early multiple sclerosis (MS), IM score revealed a profound fragmentation of IgA-mediated immune engagement, particularly among short-chain fatty acid–producing bacteria and dominant archaeal lineage. These patterns are not captured by standard diversity or compositional metrics. To capture community-level organization, we aggregated IM score values into the Immunologically Engaged Gut Microbiota Index (IMG index ). Using IMG index , we tracked disruptions in IgA-mediated immune engagement in early MS and observed its sensitivity to changes following fecal microbiota transplantation and fluctuations in disease activity. This demonstrates the potential of IMG index to monitor both disease-associated alterations and therapeutic responses. Conclusion These findings establish IgA-mediated immune surveillance as a quantifiable axis of gut microbiota organization, providing an ecological framework for understanding host–microbe interactions.