Intermittent Fasting Alleviates Anesthesia/Surgery‐Induced Delirium‐Like Behavior in Aged Mice by Remodeling Gut Microbiota

TL;DR

Intermittent fasting before surgery helps prevent delirium in old mice by improving gut bacteria and brain mitochondria.

Contribution

This study shows intermittent fasting prevents delirium via gut microbiota and mitochondrial mechanisms in aged mice.

Findings

Preoperative intermittent fasting reduced delirium-like behaviors in aged mice after surgery.

IF preserved gut microbiota and short-chain fatty acids, supporting hippocampal mitochondrial health.

Fecal microbiota transfer and SCFA supplementation replicated IF's protective effects.

Abstract

Postoperative delirium (POD) is a serious complication in elderly patients, associated with prolonged recovery and adverse outcomes. Recent evidence links POD to mitochondrial dysfunction. While intermittent fasting (IF) has been shown to enhance mitochondrial function and exert neuroprotective effects, potentially through gut microbiota modulation, its ability to prevent POD and the underlying mechanisms remain unclear.

We examined the effects of preoperative IF on delirium‐like behavior in aged mice following anesthesia/surgery. Assessments included neurobehavioral tests, gut microbiota composition, fecal shortchain fatty acids (SCFAs), hippocampal synaptic and mitochondrial ultrastructure via transmission electron microscopy, mitochondrial function, and related molecular markers. To establish causality, fecal microbiota transplantation and SCFA supplementation experiments were conducted.

Preoperative IF significantly attenuated anesthesia/surgery‐induced delirium‐like behaviors. Mechanistically, IF reshaped the gut microbiota and preserved SCFA levels, which collectively maintained hippocampal mitochondrial homeostasis. Both fecal microbiota transplantation and SCFA supplementation replicated the protective effects of IF, confirming the causal role of gut microbiota and its metabolites.

These findings demonstrate that preoperative intermittent fasting mitigates delirium‐like behavior by modulating the gut microbiota–SCFA–mitochondrial axis, highlighting its potential as a non‐pharmacological strategy to enhance neurocognitive resilience and prevent POD in elderly surgical patients.

Preoperative intermittent fasting alleviates postoperative delirium‐like behaviors in aged mice by remodeling gut microbiota and preserving shortchain fatty acids. This gut‐brain interaction maintains hippocampal mitochondrial dynamics and synaptic plasticity, offering a promising non‐pharmacological strategy for perioperative neuroprotection.

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