Stereoselective metabolic disruption of cypermethrin by remolding gut homeostasis in rat

Cypermethrin (CYP), a prototypical synthetic pyrethroid, reportedly causes metabolic disruption, while its stereoselective impact remains elusive. This study initially revealed that only α-CYP caused significant weight loss at 8.5 mg/(kg•day) in rats. All three CYP isomers caused the accumulation of hepatic glycogen, and hyperlipemia phenotype as the increment of total triglyceride. Rats treated with α-CYP had markedly high blood glucose levels and homeostasis model assessment of insulin resistance index. The systematic inflammation of θ-CYP group rats was evidenced by high lipopolysaccharide-binding protein levels and abnormalities of leukocytes indices. By examining the gut microbiome, we found that α-CYP-treated rats had low contents of Firmicutes and high levels of Verrucomicrobia while Elusimicrobia was enriched in the β-CYP group. The increasing alpha diversity in the θ-CYP group may be due to the dominance of pathogenic bacteria and the increase of probiotics to counteract adverse effects. Exclusively, the α-CYP group enriched total short-chain fatty acids (SCFAs), whereas most SCFAs depleted in the θ-CYP group. The correlation analysis further found Firmicutes, an energy storage modulator, was positive to body weight (BW), while SCFAs exerted the opposite, confirming the low BW in α-CYP. Blood glucose that correlated well with SCFAs and Verrucomicrobia can be accounted for the discrepancy between α-CYP and θ-CYP. Overall, the three isomers exerted stereoselective glycolipid disruption in rats, and gut homeostasis acted as vital indicators. [Display omitted]