Fetal Exposure to Acetochlor Impaired Cognitive Function in Rats via Abnormal Gut Microbiome and Metabolic Disorders

Background: Current evidence has shown that acetochlor has adverse effects on health, which has been widely used in agricultural production, while the evidence on the effects of fetal acetochlor exposure on nervous system is quite limited. The fetus period is the most sensitive window period in the whole lifetime to external stimuli. Therefore, we established a rat model fetal exposed to acetochlor. Results: Impaired cognitive function, abnormal gut microbiome and significant changes in the hippocampus and colon could be observed in the acetochlor-exposed group. We also observed remarkable impairment in the hippocampal cells in the histomorphology observation. Fecal microbiota transplantion(FMT) was performed to elucidate whether the gut microbiome mediated the acetochlor-induced abnormal behavior. Then the proteomics analysis and metabonomics analysis in the hippocampus indicated that differential expression proteins were mainly enriched in amino acid neurotransmitter-related pathways, long-term potentiation, and synaptic-related pathways and differential metabolite were mainly enriched in mutiple neurotransmitter-related pathways. Then we observed remarkable changes in the Camk2b/Erk1/2/NF-κB pathway and Prkaca/p-CREB1/BDNF pathway in the FMT group, which may cause abnormal cognitive behaviors. Conclusions: Our results demonstrate that fetal exposure to acetochlor could induce abnormal behaviors in rats via disrupting the intestinal microbiome.