Chronic alcohol use is a significant explanation for liver damage and death: Roughly 30,000 individuals in the US die annually from alcoholic liver diseases, resembling cirrhosis. Among the many negative impacts of excessive alcohol use is its ability to adversely affect the gut microbiome, though how that happens has been a mystery, since the vast majority of consumed alcohol is absorbed within the mouth and stomach and doesn’t reach the intestines.

In a latest study, published August 8, 2022 in Nature Communications, researchers at University of California San Diego, with colleagues elsewhere, propose a solution: Reprogramming of gut microbiota is brought on by acetate produced by the liver diffusing back into the intestines where it becomes a carbon source to support bacterial growth.

You’ll be able to consider this a bit like dumping fertilizer on a garden. The result’s an explosion of imbalanced biological growth, benefitting some species but not others.”

Bernd Schnabl, MD, professor of drugs and gastroenterology at UC San Diego School of Medicine, co-corresponding creator

Acetate is a nutrient utilized in cellular metabolism and has roles in appetite regulation, energy expenditure and immune response. In moderate levels, it promotes overall health, from improved cardiac function to enhanced red blood cell production and memory function. In excessive levels, it’s related to metabolic changes linked to disease, including cancer.

In the most recent study, Zengler and colleagues fed mice a molecule that might be broken down into three acetates within the rodents’ gut. The researchers noted the animals’ intestinal microbiota were altered by the extra acetate in a way much like what they observed when feeding alcohol to the mice, but without damaging effects to their livers.

“Chronic alcohol consumption is related to lower intestinal expression of antimicrobial molecules. Individuals will alcohol-related liver disease commonly have bacterial overgrowth of their guts,” said Zengler. “These findings suggest that microbial ethanol metabolism doesn’t contribute significantly to gut microbiome dysbiosis (imbalance) and that the microbiome altered by acetate doesn’t play a significant role in liver damage.”

“The situation is more complicated than previously assumed. It isn’t so simple as more ethanol equals microbiome changes and thus, microbiome dysbiosis equals more liver disease. While this finding doesn’t translate to imminent latest treatments for alcoholic liver disease, it should help to delineate the effect of acetate on the microbiota and help refining future study designs.”

The authors said the findings are necessary because they move the investigation past whether “changes within the gut microbiome are related to ethanol consumption per se are critical … and towards identifying bacteria which might be causal for deleterious effects of alcohol consumption, slightly than side-effects either of consumption or disease.”

Source:

University of California – San Diego

Journal reference:

Martino, C., et al. (2022) Acetate reprograms gut microbiota during alcohol consumption. Nature Communications. doi.org/10.1038/s41467-022-31973-2.