Dietary cypermethrin exposure reshapes the rumen microbiota and enriches antibiotic resistance genes: Metagenomic evidence of co-selection.
Pesticide residues in crop-derived feedstocks represent a pervasive environmental stressor in agro-ecosystems, yet their role in driving the non-antibiotic co-selection of antimicrobial resistance (AMR) within the ruminant gut reservoir remains poorly understood. This study investigated the physiological trade-offs and indirect mechanisms of resistome expansion in a ruminant model exposed to environmentally relevant levels of cypermethrin. Integrated metagenomic and phenotypic assays revealed that cypermethrin exposure did not impair growth performance, but significantly increased daily feed intake and shifted fermentation profiles toward acetate. This metabolic compensation was supported by a reshaped core microbiome, characterized by increased abundance of fibrolytic consortia (e.g., Fibrobacter, Ruminococcus), enrichment of carbohydrate-active enzymes (GH3, GH5, GH13, and GH43), and upregulation of glycolysis and acetate-producing pathways. However, this metabolic adaptation came at a severe physiological cost, evidenced by systemic oxidative injury and hepatic dysfunction in the host. Crucially, cypermethrin acted as a potent non-antibiotic selective agent that expanded the ruminal resistome and mobilome, specifically, enriching efflux pumps (e.g., oqxA, MexB) confirmed target alteration genes (e.g., vanE). Consequently, dietary cypermethrin exposure forces microbial metabolic compensation at the expense of host hepatic health, while turning the ruminant gut into an overlooked repository for AMR. These findings highlight the critical ecological risks of pesticide-induced resistance co-selection, threatenting the One Health framework. Future research should incorporate multi-dose gradients, evaluate long-term exposure effects using sequential temporal sampling, and utilize non-invasive baseline monitoring across diverse ruminant species to fully elucidate these ecological risks.