Postoperative delirium after cardiac surgery associated with perioperative gut microbiota dysbiosis: Evidence from human and antibiotic-treated mouse model.

Summary

In matched off-pump CABG patients, postoperative delirium was preceded by perioperative gut dysbiosis characterized by reduced alpha diversity, increased Enterococcus, and loss of SCFA-producing genera; fecal SCFAs were reduced and correlated inversely with delirium severity and inflammation. FMT from POD patients induced delirium-like behavior and neuroinflammation in antibiotic-treated mice.

Key Findings

• Postoperative delirium patients showed lower alpha diversity and distinct microbiota with increased Enterococcus and reduced SCFA-producing genera (e.g., Bacteroides, Ruminococcus).
• Fecal SCFA levels were significantly reduced in POD and inversely correlated with delirium severity and plasma inflammation.
• FMT from POD patients induced delirium-like behavior and neuroinflammation in antibiotic-treated mice, suggesting a transferable microbiome-mediated effect.

Clinical Implications

Supports exploration of microbiome-informed risk stratification and preventive strategies (e.g., preserving SCFA producers, nutrition, antibiotic stewardship) to reduce POD after cardiac surgery.

Limitations

• Single-center study with modest human sample size (n=60 matched), limiting generalizability.
• Human component is observational; mice were antibiotic-treated rather than germ-free, and causal pathways require further dissection.

Future Directions

Randomized trials testing microbiome/SCFA-preserving interventions, mechanistic dissection of microbial metabolites, and validation across surgical populations.