Drunkenness and anti-drunkenness of alcoholic beverages from the gut-liver-brain axis perspective: A review

Alcohol consumption has become prevalent to contemporary societies. The WHO has launched the Global Alcohol Action Plan 2022–2030 to raise awareness of alcohol-related hazards, diminish alcohol consumption to advance public health via multi-sectoral collaboration. This review synthesizes evidence on the mechanisms of drunkenness and anti-drunkenness, emphasizing the gut-liver-brain axis as the central regulatory network. It highlights how alcohol and its metabolites, including acetaldehyde and higher alcohols, disrupt this axis by compromising gut barrier integrity, inducing hepatic oxidative stress, and triggering neuroinflammation. These effects occur through interactions with cellular components, the generation of reactive oxygen species, and the inhibition of ADH and ALDH activities via neurochemical pathways. The review also evaluates the potential of natural products to anti-drunkenness by targeting bidirectional interactions among the gut, liver, and brain. A hierarchical framework is proposed: upstream interventions accelerate ethanol metabolism by ADH/ALDH and GABA-glutamate modulation; midstream block oxidative and inflammatory cascades via CYP2E1/ROS pathway; downstream mechanisms repair intestinal and hepatic damage via microbiota regulation and endotoxin-TLR4-NF-κB pathway, ultimately regulating the gut-liver-brain axis. This framework could provide directions for the future investigations into the particular-processes behind intoxicated behavior, and aid in the development of anti-drunkenness therapies.