Effects of Perioperative Exposure on the Microbiome and Outcomes From an Immune Challenge in C57Bl/6 Adult Mice.

Summary

In a mouse perioperative exposure model (fasting, volatile anesthesia, supplemental oxygen, cefazolin, buprenorphine), 16S rRNA profiling showed transient reductions in diversity with loss of health-associated commensals and altered amino acid metabolic pathways. Fecal microbiota from day 3 post-exposure transferred to secondary abiotic mice reduced 7-day survival after endotoxemia (~20% vs ~70%). This provides mechanistic evidence that common perioperative factors, independent of surgery, induce dysbiosis that worsens host response to inflammation.

Key Findings

• A perioperative exposure bundle (12 h fasting, 4 h volatile anesthesia, 7 h oxygen, cefazolin, buprenorphine) induced transient gut microbial dysbiosis with reduced biodiversity and loss of Lactobacillus, Roseburia, and Ruminococcus.
• Inferred microbiota-mediated amino acid metabolic pathways were altered after exposure.
• Fecal microbiota from day 3 post-exposure reduced 7-day survival after endotoxemia in secondary abiotic mice (~20% vs ~70%, P=0.0002).

Clinical Implications

Highlights the need for stewardship of antibiotics, oxygen, and opioids, and consideration of nutritional strategies, to minimize perioperative dysbiosis; motivates trials of microbiome-preserving or -restoring approaches (e.g., probiotic/prebiotic timing) around surgery.

Limitations

• Preclinical mouse model; generalizability to humans requires validation
• 16S-based inference lacks strain-level and metabolomic resolution

Future Directions

Human perioperative studies assessing microbiome trajectories and testing interventions (antibiotic stewardship, oxygen titration, nutrition, probiotics/prebiotics) to mitigate dysbiosis and postoperative inflammatory complications.