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.

Investigating human-derived lactic acid bacteria for alcohol resistance

“…Thus, the results vary with the probiotic bacterial strains, indicating that selection of probiotic strain(s) with high ethanol-and acetaldehyde-metabolizing abilities is essential. Other studies have attempted to increase alcohol degradation in the intestine after oral administration by designing recombinant bacterial strains, such as Lactococcus lactis expressing human ADH1B [31], Bacillus subtilis co-expressing ADH and ALDH [32], and Escherichia coli Nissle 1917 co-expressing ADH and ALDH [33]. However, the safety of these recombinant probiotics for human use remains uncertain.…”

Gut microbiome in alcohol use disorder: Implications for health outcomes and therapeutic strategies-a literature review

“…Most recently, a recombinant probiotic Lactococcus lactis expressing human ADH1B (hADH1B) was constructed, to enhance alcohol degradation in the intestinal tract after oral administration. Alcohol’s metabolism includes its decomposition from the enzyme alcohol dehydrogenase the action of which is followed by the liver enzyme ALDH; thus, as expected, the administration of hADH1B-expressing probiotic reduced alcohol absorption, and extended alcohol tolerance time and a reduction of recovery time and protected the intestine and liver from damage after acute alcohol consumption in mice[ 82 ].…”