Gut Microbiota Influences Developmental Anesthetic Neurotoxicity in Neonatal Rats.

Summary

Neonatal rats exposed to sevoflurane (2.1% for 2 h on P7–P13) developed spatial learning deficits with gut dysbiosis (↓Lactobacillus; ↑Roseburia, Bacteroides). Fecal microbiota transplantation from healthy adults increased α-diversity, boosted butyrate-producing taxa (Firmicutes/Ruminococcus), raised fecal butyrate, induced hippocampal histone acetylation and BDNF mRNA, reduced neuroinflammation/apoptosis, and improved reversal Morris water maze performance.

Key Findings

• Sevoflurane altered gut microbiota: ↑Roseburia (effect 1.01) and ↑Bacteroides (1.03), ↓Lactobacillus (−1.20).
• FMT increased α-diversity and butyrate-producing taxa (Firmicutes effect 1.44; Ruminococcus 1.69), raised fecal butyrate.
• FMT induced hippocampal histone acetylation and BDNF mRNA, suppressing neuroinflammation and neuronal apoptosis.
• Behaviorally, FMT improved latency to target (P=0.019) and target-zone crossings (P<0.001) in reversal Morris water maze.

Clinical Implications

While preclinical, findings support exploring microbiota-modulating strategies (e.g., probiotics, prebiotics, dietary fiber, SCFA augmentation) to mitigate neurodevelopmental risks after pediatric anesthesia.

Limitations

• Preclinical neonatal rat model limits direct clinical extrapolation
• FMT donor variability and lack of metabolite-specific causality experiments (e.g., butyrate supplementation alone)

Future Directions

Test defined probiotic/SCFA interventions and causality via gnotobiotic models; longitudinal neurodevelopmental outcomes after anesthesia with microbiome modulation.