LDH-based avermectin nanopesticide modulates bioaccumulation, antioxidant responses, and microbiota stability in...

Nanopesticides offer a promising route to improve the safety and environmental performance of conventional agrochemicals by leveraging their small size and structured surfaces to modify behavior within the earthworm gut. Here, a Mg/Al-LDH nanocarrier loaded with avermectin (LDHs-AVM) was synthesized and characterized by plate-like, hexagonal morphology with nanoscale dimensions (<100 nm). Earthworm bioaccumulation assays showed that LDHs-AVM, despite slightly lower peak tissue levels than AVM (0.13-0.17 and 0.15-0.20 mg/kg), persisted longer, indicating formulation-dependent enhancement of stability. Consistent with these kinetic profiles, histopathology revealed that AVM induced severe epidermal and intestinal lesions, whereas LDHs-AVM caused only mild structural disturbances, demonstrating substantial attenuation of tissue toxicity. Gut biomarker assays further showed reduced oxidative damage and enhanced antioxidant/detoxification responses under LDHs-AVM exposure, confirming mitigation of AVM-induced oxidative stress. Fluorescence imaging demonstrated strong intestinal enrichment of LDHs-AVM with limited systemic diffusion, supporting gut-targeted biodistribution (0.094 and 0.041 mg/kg). At the microbiome and transcriptome levels, NGS profiling showed that LDHs-AVM enhanced microbial diversity while AVM caused marked dysbiosis, and RNA-seq indicated far fewer DEGs with suppression of AVM-activated PI3K-AKT/MAPK stress pathways, together evidencing mitigation of AVM-induced molecular disruption. Collectively, these results demonstrated that LDHs-AVM reduces toxicity, preserves gut microbial homeostasis, and enhances intestinal protection in Eisenia fetida, establishing an integrated framework for nanopesticide safety assessment and highlighting LDH-based systems as promising platforms for sustainable and environmentally responsible agrochemical design.