Mechanistic Pathways of Pesticide-Induced Intestinal Injury: Oxidative Stress, Inflammation, and Barrier Dysfunction
Nathalia Kirsten, Shayane Milhorini da Silva, Camila Bach de Assis, Salvador Paganella Chaves Júnior, Izonete Cristina Guiloski, Daniele Maria-FerreiraPesticides are among the most widely used environmental contaminants worldwide, resulting in continuous human exposure primarily through dietary intake. As a major site of contact following oral exposure, the gastrointestinal tract represents a relevant target for pesticide-associated toxicity. Although accumulating evidence indicates that pesticides can alter intestinal structure and function, the toxicological mechanisms underlying these effects have not been critically integrated. This narrative review evaluates experimental studies in rodent models investigating the intestinal toxicity of herbicides, insecticides, and fungicides, with particular emphasis on the convergence and heterogeneity of the reported mechanisms. Across the studies reviewed, recurrent alterations included oxidative imbalance, inflammatory activation, epithelial barrier disruption, changes in intestinal permeability, mitochondrial dysfunction, and genotoxicity. However, the occurrence and magnitude of these responses varied according to pesticide class, compound, dose, exposure duration, formulation, and experimental model, and the available evidence does not support a universal mechanistic sequence. By comparatively integrating these findings, this review highlights shared and pesticide-specific intestinal responses while distinguishing recurrent associations from established causal relationships. Important knowledge gaps remain regarding chronic low-dose exposure, pesticide mixtures, sex-specific susceptibility, recovery after exposure, and the translational relevance of experimental findings to humans. Overall, this review provides a critical framework for interpreting pesticide-associated intestinal toxicity and identifies priorities for future experimental and translational research.