Antibiotic disruption of the gut microbiome triggers IBD-like proteolytic activity.

Antibiotics (Abx) are essential in medicine but can disrupt gut microbiota, potentially contributing to inflammatory bowel diseases (IBDs). This study employed fecal metagenomics and metaproteomics to evaluate the effects of Abx in patients with pouchitis, ulcerative colitis (UC), and non-IBD controls. Each group displayed distinct microbiome profiles, with metaproteomes more affected by Abx than metagenomes. Proteomic analysis revealed increased pancreatic protease activity and fecal proteolytic activity in all groups, except in patients without IBD before Abx, consistent with impaired epithelial barrier integrity. Abx also decreased bacterial protease inhibitors, which may control proteolysis and help maintain gut balance. These findings emphasize the importance of understanding Abx-induced proteolytic shifts in IBD and highlight metaproteomics as a valuable tool for studying host-microbiome interactions. Future research should explore the molecular mechanisms that regulate bacterial protease inhibitor levels and their effects on intestinal health.