Effects of repeated sevoflurane inhalation on cognitive deficits mediated by the gut-brain axis

This study was designed to determine the effects of repeated sevoflurane (Sev) exposure on children and the possible role of the gut-brain axis. Thirty 28-day Sprague-Dawley rats were randomly divided into five experimental groups. The Sev group was exposed to 3.2% Sev for 2 h on postnatal day (P) 35, P42, and P49. The Sev-Con group only inhaled carrier gas for 2 h at the same time points. The ANT group received antibiotic pre-treatment only since P28 for 3 weeks. The Sev + ANT group was treated with antibiotics for 3 weeks and then exposed to 3.2% Sev for 2 h at each time point. Control group (Con group): animals were freely raised without special treatment. Behavioral tests performance significantly decreased in the Sev group compared to the other groups. Sev exposure promoted serum levels of LPS and TMAO, as well as levels of IL-1β, IL-6, TNF-α, LPS, and TMAO in hippocampal tissue, reduced the expression of ZO-1 in colon tissue and hippocampal vascular tissue, and activated the TLR4/NF-κB/NLRP3 inflammatory pathway in hippocampal tissue. After ANT treatment, the expression of related proteins improved. There were no significant changes in levels of short-chain fatty acids (SCFAs) between groups. Finally, the 16S rRNA sequencing indicated that at the genus level, Ligilactobacillus , Faecousia , and Alloprevotella showed an increasing trend, while Lactobacillus showed a decreasing trend. The results may reflect that repeated Sev anesthesia may induce learning and memory deficits through the gut-brain axis at the developmental stage.