Novel insight into the mechanisms of neurotoxicity induced by type I and type II pyrethroids via disrupting the gut-brain axis in lizards

Type I and type II pyrethroids are widely used and frequently detected in agricultural environments. The neurotoxic effects and underlying mechanisms of pyrethroids in native animal populations, including lizards as common farmland inhabitants, remain unclear. This study exposed male lizards (Eremias argus) to type I bifenthrin (BF) and type II fluvalinate (FA) pyrethroids for 28 days, resulting in abnormal behaviors. Targeted analyses indicated that neurotransmitters, including dopamine, GABA, acetylcholine, and choline in lizard plasma, were significantly decreased with alterations in the cholinergic synapse, dopaminergic synapse, and cAMP signaling pathway in the brain after BF and FA treatment. Nervous system-related genes such as CACNA1A, CACNA1B, and CACNA1C were significantly down-regulated and highly correlated with arachidonic acid metabolism pathway-related metabolites in lizard gut. A notable decrease in metabolites within the arachidonic acid metabolism pathway and alterations in the gut microbiome were indicative for anti-inflammatory responses and neurotoxic effects. Interestingly, increased type I BF bioaccumulation in lizard intestines induced a higher abundance of Akkermansia, which resulted in reduced inflammation in the gut and lower neurotoxic effects compared to the low-dose BF exposure group. This study reveals contrasting dose-responses between pyrethroid types and suggests gut-brain axis-regulated neurotoxicity in lizards.