Author: Khan ZA et al.
Anesthesiology, September 10, 2025. doi:10.1097/ALN.0000000000005745
This experimental study investigated how paternal sevoflurane exposure in rats affects the brain-gut-microbiome (BGM) axis across generations. Male rats exposed to sevoflurane prior to mating produced male offspring with significant abnormalities: exaggerated stress responses, hippocampal transcriptomic changes, gut microbiota dysbiosis, systemic inflammation, higher LDL cholesterol, and increased body weight. Female offspring exhibited only altered microbial diversity.
In exposed fathers, hippocampal transcriptomes showed profound changes, though gut microbial diversity was the only affected parameter. Importantly, pretreatment of sires with bumetanide (NKCC1 inhibitor) or RU486 (glucocorticoid receptor inhibitor) largely prevented offspring BGM and neurocognitive abnormalities—except for persistent weight gain in male offspring.
These findings highlight a novel link between anesthetic exposure, intergenerational neurocognitive vulnerability, and the BGM axis, suggesting therapeutic opportunities for mitigating risk.
What You Should Know
• Paternal sevoflurane exposure altered the BGM axis in offspring, especially males.
• Offspring exhibited heightened stress responses, inflammation, dysbiosis, and metabolic changes.
• Female offspring were less affected, showing only microbial diversity shifts.
• Bumetanide and RU486 pretreatment prevented most intergenerational abnormalities.
• Findings suggest paternal exposures may influence perioperative neurocognitive disorder (PND) risk via BGM disruption.
Thank you to Anesthesiology for making this work available.