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

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 taxa explicitly targeted by IgG. 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. Functional profiling indicated the enrichment of pathways related to host-derived mucin degradation, capsular polysaccharide biosynthesis, and amino acid biosynthesis. Furthermore, Random Forest machine learning models utilizing optimized IPS features achieved an area under the curve of 0.817 for predicting UC exacerbation and 0.843 for predicting C-reactive protein elevation. In conclusion, systemic IgG responses in UC were selectively directed toward 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 immune-targeted bacteria that fluctuate across different disease phases.