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Intermittent Fasting Alleviates Anesthesia/Surgery-Induced Delirium-Like Behavior in Aged Mice by Remodeling Gut
Peiying Huang1,2, Longlu Cao2,3, Tianyu Cao2
1Postdoctoral Mobile Station, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
CNS Neuroscience & Therapeutics
|January 22, 2026
Summary
Preoperative intermittent fasting (IF) prevents delirium-like behavior in aged mice by improving gut microbiota and preserving mitochondrial function. This highlights IF as a potential non-pharmacological strategy for elderly surgical patients.
Area of Science:
- Neuroscience
- Gerontology
- Metabolic research
Background:
- Postoperative delirium (POD) is a significant complication in elderly patients, linked to mitochondrial dysfunction.
- Intermittent fasting (IF) shows potential for neuroprotection and mitochondrial enhancement, but its role in POD prevention is unclear.
Purpose of the Study:
- To investigate the effects of preoperative IF on delirium-like behavior in aged mice.
- To elucidate the underlying mechanisms, focusing on the gut microbiota-mitochondrial axis.
Main Methods:
- Aged mice underwent anesthesia/surgery with or without preoperative IF.
- Assessments included neurobehavioral tests, gut microbiota analysis, SCFA levels, and hippocampal mitochondrial/synaptic ultrastructure.
- Causality was tested via fecal microbiota transplantation and SCFA supplementation.
Main Results:
- Preoperative IF significantly reduced delirium-like behaviors post-surgery.
- IF modulated gut microbiota, preserved SCFA levels, and maintained hippocampal mitochondrial homeostasis.
- Fecal microbiota transplantation and SCFA supplementation mimicked IF's protective effects.
Conclusions:
- Preoperative intermittent fasting mitigates delirium-like behavior via the gut microbiota-SCFA-mitochondrial pathway.
- This suggests IF is a promising non-pharmacological approach to enhance neurocognitive resilience and prevent POD in elderly surgical patients.
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