Maternal intestinal dysbiosis mediated by sevoflurane exposure during pregnancy leads to altered gut microbiota and metabolites and cognitive dysfunction in the offspring

Abstract

Prenatal exposure to anesthetic drugs, such as sevoflurane, may exert a long-lasting impact on neurological function in the offspring. This study aims to investigate the consequence of prenatal sevoflurane exposure on cognitive function in offspring mice. C57BL/6 J mice of 2–3 months of age were housed under standard environmental conditions. Pregnant mice were randomly assigned to receive either sevoflurane exposure or to serve as control group. Behavioral tests conducted included the novel object recognition test and the Morris water maze test. During the terminal phase of the experiment, fecal samples from the mother and offspring, as well as serum and hippocampal samples from the offspring, were collected for microbiome and metabolomic analyses. Behavioral experiments showed that cognitive function was impaired in the offspring mice of the anesthetized group. In addition, sevoflurane altered the gut microbiota composition in pregnant mice and their offspring, with reduced Prevotella abundance in the anesthetized group. Metabolomics analyses showed that anesthetized and control offspring also exhibited significant differences in metabolites in fecal, serum, and hippocampal samples, particularly in the glycerophospholipid metabolism pathway. Further correlation analyses showed a significant correlation between the gut microbiota (especially Prevotella) and differential metabolites in the hippocampus. These results indicate that prenatal sevoflurane exposure disrupts gut microbiota and metabolic pathways, potentially contributing to cognitive deficits in offspring via the gut-brain axis, highlighting risks of anesthesia during pregnancy on fetal neurodevelopment.