Host detoxification and gut microbiota are associated with chlorantraniliprole resistance in Spodoptera frugiperda.

Spodoptera frugiperda is a major agricultural pest that causes severe damage in China. Chlorantraniliprole (CAP) is the primary insecticide used for control; however, it is yet unknown how much the intrinsic detoxification system and gut microbiota of the host contribute to resistance. In this study, we used a resistant strain (CR) with a 71.85-fold resistance ratio after 10 generations of CAP selection. The molecular and microbial changes associated with CAP resistance in S. frugiperda were systematically analyzed by integrating phenotypic and multi-omics data. Results demonstrated that detoxification enzyme activities were markedly increased in the CR strain. Host-mediated metabolic pathways driven by Cytochrome P450 and glutathione S-transferase were significantly upregulated. Furthermore, transcriptome evidence indicated that CAP-induced calcium dysregulation was mitigated via enhanced calcium sequestration and endoplasmic reticulum chaperone responses, suggesting physiological tolerance of insects to this insecticide.. Continuous CAP stress also significantly reshaped the gut microbial community structure of S. frugiperda, with Enterococcus emerging as the dominant genus. According to metagenomic annotation, the gut microbiome was enriched in candidate genes associated with CAP degradation, including dehalogenases and amidases, that could potentially break the chemical bonds in CAP and thereby contribute to resistance. Enterococcus mundtii was the most prominently contributor in terms of gene abundance. Phylogenetic analysis revealed sequence similarities and conserved domains between candidate microbial degradation genes and host metabolic detoxification genes, suggesting potential functional similarity. The integrative analyses suggested that S. frugiperda resistance may arise from correlated changes in host endogenous metabolism, calcium homeostasis, and gut-microbiota-mediated degradation potential. The gut microbiota may form a coordinated adaptive regulatory system by encoding candidate degrading enzymes and exhibiting correlative coupling with host genes, which requires further functional validation. These findings highlight the potential synergy between host detoxification and gut microbiota as a contributing factor to CAP resistance in S. frugiperda.