Alcohol consumption impacts microbiome? Scientists unravel mechanism to further liver disease research

15 Aug 2022 --- Scientists from the University of California (UC) San Diego are revealing how the chronic use of alcohol – the majority of which is absorbed by the mouth and stomach before it reaches the intestines – may still adversely affect the microbiome. However, the authors hold that researchers must be wary of assuming too much in this relation.

According to the study published in Nature Communications, the microbiome makeup changes not as a result of the interaction of ethanol and microbiota but by the release of acetates by the liver. The alcohol causes the acetates to diffuse back into the intestines. Once there, the acetates become a source of carbon for bacterial growth.

“The situation is more complicated than previously assumed,” says Dr. Karsten Zengler, professor, pediatrics and bioengineering at UC San Diego School of Medicine and Jacobs School of Engineering. “It’s not as simple as more ethanol equals microbiome changes, and thus, microbiome dysbiosis equals more liver disease.”

“While this finding does not translate to imminent new treatments for alcoholic liver disease, it will help to delineate the effect of acetate on the microbiota and help refine future study designs.”

Too much of a good thing?Alcohol-related liver disease is associated with microbiome imbalances.
The nutrient acetate helps to regulate appetite, immune response and even cellular metabolism. At normal levels, it promotes cardiac function, memory function, red blood cell production and overall health. However, at excessive levels, it has been linked to diseases such as cancer.

In this study, mice were fed a molecule that their guts could break down into three different acetates. The acetates changed the mice’s microbiome in similar ways to the mice that were fed alcohol. However, the acetates did not induce liver damage as the alcohol did.

“You can think of this a bit like dumping fertilizer on a garden,” explains Zengler.

“The result is an explosion of imbalanced biological growth, benefitting some species but not others,” Dr. Bernd Schnabl, professor, medicine and gastroenterology, UC San Diego School of Medicine, elaborates. 

Though recent studies have shown that some alcohol can be good for the microbiome, people with alcohol-related liver disease (ALD) often display changes in the amount of Bacteroidetes and Enterococcaceae but the authors affirm that this can be caused by many other things as the consumption of starches.

Moving the needle
The authors hold that the importance of the study lies in how the findings can help researchers to clarify what is causing their microbiome changes in patients suffering from the effects of chronic alcohol consumption.

The study notes that patients with ALD have altered microbiomes and often have bacterial overgrowth in the intestines. However, the authors hold that studies focused on alcohol consumption may be revealing the effects of acetates which, although they can be released by the liver, can also come from numerous nutrition sources.The researchers state that acetates released by the liver and not the alcohol itself is what changes the microbiome.

Moreover, they could be seeing the effects of natural microbiome variations in individual patients. According to the authors, these findings reveal that studies focused on how alcohol harms the microbiome will have to “detrend” for these factors. However, they also state that ruling out possible causes can help future researchers find the root causes.

“Critical” steps forward
The study also discusses the possible mistakes that not including its findings in future research could cause. It points to the initial attribution of changes in the microbiome to Type II diabetes that were later found to be the result of metformin, a treatment for diabetes.

“Persons with ALD commonly have bacterial overgrowth in their guts,” says Zengler. “These findings suggest that microbial ethanol metabolism does not contribute significantly to gut microbiome dysbiosis (imbalance) and that the microbiome altered by acetate does not play a major role in liver damage.”

“Understanding whether the gut microbiome directly metabolizes ethanol and whether changes in the gut microbiome are related to ethanol consumption per se is critical for moving beyond microbiome associations and towards identifying bacteria that are casual for deleterious effects of alcohol consumption, rather than side effects either of consumption or disease,” the study reads.

Edited by William Bradford Nichols