Recurrent amoxicillin exposure disrupts colonic homeostasis through oxidative stress, DNA repair dysregulation, and gut dysbiosis-driven inflammation.

The present study investigated the impact of recurrent amoxicillin exposure on colonic health in a mouse model, applying a multi-parametric approach. Twenty animals were randomly divided into two groups, out of which one group received oral amoxicillin (100 mg/kg BW), administered every other week for twelve weeks. Histological and ultra-structural analyses (SEM and TEM) of colonic tissues revealed crypt degeneration, mucosal thinning, and inflammatory cell infiltration in the treated group. Biochemical assays demonstrated significantly elevated lipid peroxidation along with reduced antioxidant defences, indicative of oxidative stress. Immunohistochemistry confirmed oxidative DNA damage, accompanied by aberrant expression of DNA repair genes, indicating impaired genomic maintenance. Faecal microbiota profiling showed a pronounced loss of microbial load and enrichment of opportunistic pathogens, alongside a paradoxical increase in short-chain fatty acid levels. These alterations correlated with significantly upregulated inflammatory gene expression (TNF-α, IFN-γ, IL-6, IL-17 & IL-1β), indicating microbiome destabilization and heightened inflammatory signalling. Overall, recurrent amoxicillin exposure disrupted colonic homeostasis through dysbiosis, oxidative stress, genotoxicity, and inflammation, underscoring the potential risks of antibiotic therapy.