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 alpha-CYP caused significant weight loss at 8.5 mg/(kg center dot 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 alpha-CYP had markedly high blood glucose levels and homeostasis model assessment of insulin resistance index. The systematic inflammation of theta-CYP group rats was evidenced by high lipopolysaccharide-binding protein levels and abnormalities of leukocytes indices. By examining the gut microbiome, we found that alpha-CYP-treated rats had low contents of Firmicutes and high levels of Verrucomicrobia while Elusimicrobia was enriched in the beta-CYP group. The increasing alpha diversity in the theta-CYP group may be due to the dominance of pathogenic bacteria and the increase of probiotics to counteract adverse effects. Exclusively, the alpha-CYP group enriched total short-chain fatty acids (SCFAs), whereas most SCFAs depleted in the theta-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 alpha-CYP. Blood glucose that correlated well with SCFAs and Verrucomicrobia can be accounted for the discrepancy between alpha-CYP and theta-CYP. Overall, the three isomers exerted stereoselective glycolipid disruption in rats, and gut homeostasis acted as vital indicators. (c) 2022 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V.

Automated summary

The study reveals that alpha-CYP causes weight loss, hepatic glycogen accumulation, and hyperlipemia in rats, while theta-CYP induces systemic inflammation. The gut microbiome composition differs significantly in the alpha-CYP-treated group, with lower levels of Firmicutes and higher levels of Verrucomicrobia. Short-chain fatty acids (SCFAs) are associated with blood glucose and Verrucomicrobia, which may explain the differential effects of alpha-CYP and theta-CYP.