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 (IBDs), including Crohn disease (CD) and ulcerative colitis (UC), as suggested by periappendicular inflammation and the reported protective effect of appendectomy in UC. Despite these associations, its functional contribution remains poorly defined. Here, we performed a multiomics analysis of appendix tissue from pediatric patients with IBD 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.NEW & NOTEWORTHY Multiomics profiling of pediatric appendiceal tissue in inflammatory bowel diseases reveals reduced microbial diversity, Proteobacteria enrichment, and coordinated associations between microbial functional pathways and host immune-related transcripts. Invasive capacity of appendix-derived Klebsiella variicola further supports potential host-microbe interactions within this niche. These findings characterize the appendix as a distinct mucosal compartment in pediatric IBD and provide a foundation for future mechanistic investigation.