Immune surveillance as an organizing axis of gut microbiota structure

The gut microbiota is a key regulator of host physiology, influencing immune homeostasis, metabolism, and neuroinflammatory processes. While most microbiome studies focus on associations between disease and microbial composition, such approaches often fail to capture the functional ecology of host-microbiota interactions. The gut microbiota is continuously monitored by the host immune system, particularly through 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, leaving a critical gap in understanding how host-microbe interactions structure microbial communities and influence disease.Here, we developed an immune-informed framework to quantify IgA-mediated microbial engagement using the Species Immune Engagement Score (IMscore). IMscore integrates three key features: the degree of IgA binding to each microbe, microbial abundance, and prevalence across individuals, producing a quantitative measure of how actively the immune system targets each taxon. To capture community-level organization, we aggregated species-level IMscore into the Immunologically Engaged Gut Microbiota Index (IMGindex). IMGindex revealed disrupted immune-microbiota structure in early MS and demonstrated sensitivity to alterations that conventional metrics failed to detect.This approach offers a biologically grounded and ecologically informed framework for assessing microbiota structure, detecting disease-associated perturbations, and monitoring therapeutic impacts.