Profiling Systemic IgG-Targeted Gut Microbiota Reveals Disease Activity-Associated Bacterial Signatures in Ulcerative...

Aberrant systemic IgG responses to the gut microbiota may be implicated in the pathogenesis of ulcerative colitis (UC). In this study, we investigated IgG-targeted bacteria and their predicted functional characteristics in UC. Using fecal samples and autologous sera from 37 patients with UC and 4 healthy controls, we profiled IgG-targeted bacteria under in vitro conditions using 16S rRNA gene sequencing. To correct for background bacterial abundance, we calculated the IgG+ Probability Score (IPS), which integrates the sample-specific IgG-binding rate to isolate candidate IgG-targeted taxa. Systemic IgG responses were selectively targeted at specific bacterial taxa rather than uniformly directed toward the entire gut microbiota. Active UC and elevated systemic inflammatory markers were associated with increased IPS in oral-associated commensals, including Granulicatella, as well as mucin-degrading taxa. Predictive functional profiling indicated the predicted enrichment of pathways hypothesized to be related to host-derived mucin degradation, capsular polysaccharide biosynthesis, and amino acid biosynthesis. Furthermore, exploratory Random Forest models using IPS features highlighted candidate taxa that differed among clinical parameters (UC exacerbation, Clinical Activity Index, and C-reactive protein), although their classification performance was not independently validated. In conclusion, our in vitro profiling indicates that systemic IgG in UC has the capacity to selectively target specific bacterial taxa associated with disease activity and systemic inflammation. Analyzing the IgG-targeted microbiota via IPS profiling deepens our understanding of host-microbiota interactions in UC and provides a valuable framework for evaluating candidate immune-targeted bacteria associated with disease activity.