Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption

Abstract Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge-drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate this harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Many anti-hangover drugs are intended to increase the activity of these two enzymes, which are weakened in many people owing to gene polymorphisms. Here, we produced a high-activity human ADH1B (hADHIB)-expressing probiotic that secreted the hADH1B enzyme to decompose alcohol in the intestinal tract after oral administration. Our results showed that the oral hADHIB-expressing probiotic reduced the absorption of alcohol, prolonged alcohol tolerance time, and shortened the recovery time after drinking. Alongside, fat accumulation in liver and basal structure disorder of small intestine caused by heavy alcohol intake was improved. Therefore, the engineered probiotic has the potential to be prepared as a mate to wine. This study also demonstrated for the first time that alcohol decomposition can be catalyzed by ectopically expressed hADH1B, providing a practical basis for subsequent development of super-biological antidotes that effectively deliver multiple enzymes.