Dataset Information

Molecular Profiling of the Appendix in Pediatric Inflammatory Bowel Diseases

ABSTRACT: Clinical studies suggest a critical role for the appendix in the pathogenesis of inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), as indicated by the presence of peri-appendicular patches in UC and the beneficial effects of appendectomy in UC. However, the underlying mechanisms remain unclear. To address this gap, we characterized microbial species, associated patterns, and host-microbiota interactions in the appendix and non-inflamed regions of the colon tissue and mucus from pediatric IBD and non-IBD patients (n=15). Metagenomic analyses revealed an enrichment of Proteobacteria (p-value=0.0061) and reduced bacterial diversity in IBD patients’ appendix compared to controls. Strong correlations between host tissue and mucus microbial pathways of IBD patients highlighted a link between microbial communities and host gene expression, contributing to immune activation and inflammation in the appendix. Our findings thus provide valuable insights and a basis for mechanistic hypotheses regarding the appendix’s role in IBD pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281635 | GEO | 2026/07/14

REPOSITORIES: GEO

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			Action	DRS
		Other
	GSE281635_DESeq2analysis.xlsx	Xlsx
	GSE281635_rawCountMatrix.txt.gz	Txt

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Project description:Antibiotics (Abx) are critical in modern medicine but can induce intestinal dysbiosis, exacerbate inflammatory bowel diseases (IBD), and disrupt the gut microbiome. Moreover, Abx treatment was reported as a significant risk factor for developing IBD, yet the underlying mechanisms remain unknown. Here, we employed metagenomics and metaproteomics to investigate the impact of Abx treatment on gut microbiota composition and activity in non-IBD, pouchitis, and ulcerative colitis (UC) patients. The combined analysis revealed distinct microbiome profiles for each group and found that the metaproteomes are more susceptible to Abx-induced changes than metagenomes. Alpha diversity decreased across all cohorts during Abx treatment, with pouchitis and UC patients exhibiting dysbiosis before treatment. Taxonomic shifts, including blooms of Proteobacteria and Actinobacteria, and reductions in microbial pathway abundances were more pronounced in IBD patients. Proteomic analysis revealed an elevated abundance of host pancreatic proteases, particularly in non-IBD patients, and during Antibiotic treatment, correlating with increased proteolytic activity and impaired gut barrier function. Functional assays confirm differential fecal proteolytic activity, suggesting that bacterial protease inhibitors, which are significantly depleted during Abx treatment, regulate proteolysis and thereby maintain delicate homeostasis in the gut. Overall, our findings suggest that Abx treatment disrupts the balance between bacterial protease inhibitors and host proteases, contributing to inflammation and gut barrier disruption. This work underscores the importance of understanding Abx-induced proteolytic shifts in the context of IBD and highlights the utility of metaproteomics in elucidating host-microbiome interactions. Future research should investigate the molecular mechanisms underlying the abundance and activity of bacterial protease inhibitors, as well as their impact on gut health.

Dataset Information

Molecular Profiling of the Appendix in Pediatric Inflammatory Bowel Diseases

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