Excessive alcohol consumption can cause bacterial overgrowth in the gut, but studies in mice have shown that this imbalance does not appear to play a major role in the risk of alcoholic liver disease

Chronic alcohol consumption is a major cause of liver damage and death: approximately 30,000 people in the United States die each year from alcoholic liver disease, such as cirrhosis. Among the negative impacts of excessive alcohol consumption is its ability to negatively affect the gut microbiome, although how this happens remains a mystery, as the majority of alcohol consumed is absorbed in the mouth and the stomach and does not reach the intestines.

In a new study, published on August 8, 2022 in Nature Communicationresearchers at the University of California, San Diego, with colleagues elsewhere, offer an answer: the reprogramming of the gut microbiota is caused by acetate produced by the liver which diffuses into the intestines where it becomes a carbon source for support bacterial growth.

“You can think of this a bit like throwing fertilizer in a garden,” said co-corresponding author Karsten Zengler, PhD, a professor in the departments of pediatrics and bioengineering at UC San Diego School of Medicine and from the Jacobs School of Engineering, respectively. “The result is a burst of imbalanced biological growth, benefiting some species but not others. »

Bernd Schnabl, MD, professor of medicine and gastroenterology at UC San Diego School of Medicine, is the other corresponding co-author.

Acetate is a nutrient used in cellular metabolism and plays a role in the regulation of appetite, energy expenditure and immune response. At moderate levels, it supports overall health, from improved heart function to improved red blood cell production and memory function. At excessive levels, it is associated with metabolic changes linked to disease, including cancer.

In the latest study, Zengler and his colleagues fed mice a molecule that could be broken down into three acetates in the rodent’s gut. The researchers noted that the animals’ gut microbiota were altered by the supplemental acetate in a manner similar to what they observed when feeding the mice alcohol, but with no adverse effects on their livers.

“Chronic alcohol consumption is associated with lower intestinal expression of antimicrobial molecules. People with alcohol-related liver disease usually have bacterial overgrowth in their intestines,” Zengler said. “These results suggest that microbial ethanol metabolism does not contribute significantly to gut microbiome dysbiosis (imbalance) and that the acetate-altered microbiome does not play a major role in liver damage. »

“The situation is more complicated than previously thought. It’s not as simple as more ethanol equals microbiome changes and therefore, microbiome dysbiosis equals more liver disease. While this finding will not translate into any imminent new treatments for alcoholic liver disease, it will help delineate the effect of acetate on the microbiota and help refine future study designs. »

The authors said the findings are important because they move the investigation beyond the question of whether “changes in the gut microbiome are related to ethanol consumption per se are critical…and toward identifying the bacteria that cause the deleterious effects of alcohol consumption, rather than the side effects either”. consumption or illness. »

Co-authors include: Camerson Martino, Livia S. Zaramela, Bei Gao, Mallory Embree, Janna Tarasova, Seth J. Parker, Yanhan Wang, Huikuan Chu, Peng Chen, Kuei-Chuan Lee, Daniela Domingos Glazerani, Asama Lekbua, Maxwell Neal and Rob Knight, all at UC San Diego; Jivani M. Gengatharan and Christian M. Metallo, UC San Diego and Salk Institute for Biological Studies; and Hidekazu Tsukamoto, Southern California Research Center for ALPD and Department of Veterans Affairs Greater Los Angeles Healthcare System.

Source of the story:

Materials provided by University of California–San Diego. Original written by Scott LaFee. Note: Content may be edited for style and length.

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Excessive alcohol consumption can cause bacterial overgrowth in the gut, but studies in mice have shown that this imbalance does not appear to play a major role in the risk of alcoholic liver disease

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