Impact of Repeated Infantile Exposure to Surgery and Anesthesia on Gut Microbiota and Anxiety Behaviors at Age 6-9.

(1) Background: Preclinical as well as population studies have connected general anesthesia and surgery with a higher risk of abnormal cognitive development, including emotional development. Gut microbiota dysbiosis in neonatal rodents during the perioperative period has been reported, however, the relevance of this to human children who undergo multiple anesthesia for surgeries is unknown. Given the emerging role of altered gut microbes in propagating anxiety and depression, we sought to study whether repeated infantile exposures to surgery and anesthesia affect gut microbiota and anxiety behaviors later in life. (2) Methods: This is a retrospectively matched cohort study comparing 22 pediatric patients of less than 3 years of age with multiple exposures (≥3) to anesthesia for surgeries and 22 healthy controls with no history of exposure to anesthesia. The parent report version of the Spence Children's Anxiety Scale (SCAS-P) was applied to evaluate anxiety in children aged between 6 and 9 years old. Additionally, the gut microbiota profiles of the two groups were compared using 16S rRNA gene sequencing. (3) Results: In behavioral tests, the p-SCAS score of obsessive compulsive disorder and social phobia were significantly higher in children with repeated anesthesia exposure relative to the controls. There were no significant differences between the two groups with respect to panic attacks and agoraphobia, separation anxiety disorder, physical injury fears, generalized anxiety disorder, and the total SCAS-P scores. In the control group, 3 children out of 22 were found to have moderately elevated scores, but none of them had abnormally elevated scores. In the multiple-exposure group, 5 children out of 22 obtained moderately elevated scores, while 2 scored as abnormally elevated. However, no statistically significant differences were detected in the number of children with elevated and abnormally elevated scores. The data show that repeated anesthesia and surgical exposures in children led to long-lasting severe gut microbiota dysbiosis. (4) Conclusions: In this preliminary study, our findings demonstrated that early repeated exposures to anesthesia and surgical predisposes children to anxiety as well as long-term gut microbiota dysbiosis. We should confirm these findings in a larger data population size and with detailed analysis. However, the authors cannot confirm an association between the dysbiosis and anxiety.