Stereoselective metabolic disruption of cypermethrin by remolding gut homeostasis in rat

Cypermethrin (CYP), a prototypical synthetic pyrethroid, reportedly causes metabolic dis-ruption, 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 incre-ment of total triglyceride. Rats treated with alpha-CYP had markedly high blood glucose levels and homeostasis model assessment of insulin resistance index. The systematic inflamma-tion 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 cor-related 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

This study revealed that the alpha isomer of Cypermethrin (CYP) caused significant weight loss and hepatic glycogen accumulation in rats. It also found a correlation between changes in gut microbiome and CYP toxicity.