Effect of Targeted Probiotics on Anesthesia‐Induced Sleep Disturbances via Modulating the Gut Microbiome and Metabolites

ABSTRACT Post‐operative/post‐anesthesia sleep disturbances are a major concern to patients, impacting recovery and overall well‐being. Probiotics may offer potential benefits for sleep promotion by modulating microbial diversity and abundance. This study aimed to investigate the effect of targeted probiotic treatment on anesthesia‐induced sleep disturbances and its impact on the microbiota and metabolites in the gut and lungs. Eight‐week‐old male SD rats received a continuous inhalation of isoflurane, combined with oral yogurt treatment without or containing probiotic Lactobacillus and Bifidobacteria . Rats underwent electrode implantation and 7 days of polysomnography. 16S rRNA sequencing and untargeted metabolomic analysis from fecal and BALF samples were used to investigate the changes in the gut and lung microbiota and their metabolites. Isoflurane exposure led to sleep disturbances associated with a significant reduction in Lactobacillus and Bifidobacteria in the gut. Targeted probiotic supplementation improved post‐anesthesia sleep quality (NREM sleep time on day 1: Yogurt+ISO group 597.25 ± 100.15 vs. Probiotic+ISO group 772.77 ± 29.36 min, p = 0.002), increased the abundance of beneficial gut bacteria, and reduced wake‐related metabolites in both the gut and lungs. Correlation analysis revealed significant negative correlations between the abundance of beneficial gut flora and wake‐related metabolites (all p < 0.05). The present study first indicated that targeted probiotic treatment alleviated post‐anesthesia sleep disturbances by modulating both the gut and lung microbiota and their metabolites. These findings suggest that peri‐anesthesia probiotic treatment may be a viable strategy for improving sleep disturbances, although further clinical research into the underlying mechanisms is needed.