Host-microbe Interactions in the Appendix of Children with Inflammatory Bowel Diseases

The human appendix is traditionally considered a vestigial organ; however, clinical observations link it to inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis (UC), as suggested by peri-appendicular inflammation and reported protective effect of appendectomy in UC. Despite these associations, its functional contribution remains poorly defined. Here, we performed a multi-omics analysis of appendix tissue from pediatric IBD patients and non-IBD surgical controls (n = 15) to characterize microbial composition and host molecular landscape. Metagenomic sequencing revealed Proteobacteria enrichment and reduced microbial diversity in IBD appendices. Correlations between host transcriptomes and mucus-associated microbial pathways indicated associations consistent with host-microbe interactions linked to immune activation. Fluorescence in situ hybridization confirmed bacterial localization, and functional assays of appendix-derived Klebsiella variicola isolates demonstrated invasive capacity in vitro. Our findings suggest that the appendix represents a distinct microbial niche in pediatric IBD and may contribute to host-microbe perturbations associated with disease.