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Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
Published on: November 15, 2024
Adenosine signaling driven by the gut microbiota underlies chronic alcohol-induced anesthetic resistance
Shuangping Wang1, Ling-Yan Su1, Danfeng Lan2
1College of Food Science and Technology, Yunnan Agricultural University, No. 452 Fengyuan Road, Kunming 650201, Yunnan, China; Yunnan Provincial Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650201, Yunnan, China.
Abstract:
Chronic alcohol consumption increases anesthetic tolerance, yet the underlying in vivo mechanisms remain unclear. Here, we demonstrate that long-term alcohol exposure reduces anesthetic efficacy in both humans and mice, prolonging induction and shortening maintenance. Fecal microbiota transplantation from alcohol-exposed donors recapitulated this phenotype in naive mice, indicating a causal role of gut microbiome alterations. Metagenomic and metabolomic analyses identified elevated adenosine as a key microbiota-derived metabolite. Adenosine supplementation decreased anesthetic sensitivity, likely via downregulation of gamma-aminobutyric acid (GABA) receptors. Our findings reveal a gut microbiota-adenosine pathway mediating alcohol-induced anesthetic resistance.
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