Adenosine signaling driven by the gut microbiota underlies chronic alcohol-induced anesthetic resistance

Cell Reports 2026 Open access

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Authors: Shuangping Wang, Ling‐Yan Su, Danfeng Lan, Henggong Pan, Miao Xiong, Mengyu Yao, Yao Deng, Zhonge Fan, Yu Cao, Hejiang Zhou
DOI: 10.1016/j.celrep.2026.117015
Cited by: 2
References: 35

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.

Fields of Study & Subjects

Gut microbiota and health Alcohol Consumption and Health Effects Vagus Nerve Stimulation Research

Publication details

Journal / source
Cell Reports
Publisher
Elsevier BV
Volume
45
Issue
3
Pages
117015–117015
Publication date
18 February 2026
Language
EN