Sevoflurane-induced gut microbiota dysbiosis drives adolescent neurobehavioral deficits in neonatal rats: Protective role of eicosapentaenoic acid

To determine whether sevoflurane causes neurobehavioral abnormality by affecting the microbiota-gut-brain axis, rats were exposed to 3% sevoflurane for 2 h every day on postnatal day (PND) 6, 7, and 8. Sevoflurane exposure in the neonatal period resulted in anxiety-like behavior, social memory damage, and cognitive impairment in adolescent rats. There were significant differences in microflora β diversity between the sevoflurane exposure group and the control group on day 7 and day 21 after exposure. Sevoflurane exposure significantly reduced bacterial species, such as <i>Corynebacterium stations</i>, <i>Lactobacillus murinus</i>, etc., also decreased glyceryl palmitate, and eicosapentaenoic acid. Bioinformatics analysis indicated that specific gut microbiota and metabolites were related to behavioral changes. Notably, EPA supplementation alleviated these neurobehavioral deficits. These findings support a role for the gut microbiota and its metabolites in sevoflurane-induced neurodevelopmental injury, potentially mediated via the microbiota-gut-brain axis. Supplementation with key metabolites may provide a therapeutic strategy for mitigating such injuries.