Lambda-cyhalothrin exposure disrupts microbiota-associated bile acid metabolism and enterohepatic feedback in mice.

Abstract

Lambda-cyhalothrin (LCT) is a widely used pyrethroid insecticide frequently detected in environmental and food-associated matrices, yet its effects on host bile acid metabolism remain unclear. Male C57BL/6 mice were orally exposed to LCT for 28 days and analyzed using integrated bile acid metabolomics, hepatic and ileal gene-expression profiling, 16S rRNA sequencing, and shotgun metagenomics. LCT reduced hepatic total bile acids but increased plasma and fecal bile acids, indicating compartment-specific bile acid redistribution. This response was accompanied by hepatic Cyp7a1/Cyp27a1 downregulation, selective Cyp8b1 upregulation, altered bile acid transporter expression, and enhanced ileal FXR-FGF15-related feedback responses. LCT also remodeled gut microbial composition and altered bile acid transformation-related functional signatures, particularly those related to 7α-HSDH and 3β-HSDH. Consistently, fecal LCA, 3-ketoLCA, and isoLCA accumulated, consistent with altered microbial LCA oxidation-reduction and epimerization potential. These findings identify microbiota-associated bile acid remodeling as a potential non-neurotoxic metabolic endpoint of pyrethroid-induced gut-liver axis disturbance and provide candidate microbial and host targets for future mechanistic validation.