It’s no secret that excessive alcohol consumption damages the liver, but a new study reveals a previously unknown vicious cycle that makes that damage worse. Chronic alcohol use makes it easier for bacteria to leak out of the gut and migrate to the liver, causing further harm.
The new study, led by scientists at the University of California San Diego, examined human liver biopsies as well as mouse models of alcohol-associated liver disease. The team found that chronic alcohol use impaired the production of a cellular signaling protein called mAChR4 in the small intestine.
Lower levels of this protein were found to interfere with the formation of what are called goblet cell-associated antigen passages (GAPs). These specialized structures play a key role in teaching the immune system to respond to microbes, particularly those that escape the gut into other parts of the body, where they don’t belong.
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Without this layer of protection, gut bacteria could escape and infiltrate organs such as the liver, where they risk exacerbating the damage associated with alcohol.
Thankfully, though, it’s a two-way street. The researchers found that if they restored the function of mAChR4, GAPs would form again, which in turn repaired the immune system’s response to wayward gut bacteria, reducing liver damage.
This could be done either by using drugs to directly activate mAChR4 or by targeting related pathways that end up having the same effect.
While the most direct health benefits would of course come from reducing alcohol intake, that’s not always as simple as it sounds. The team says that targeting mAChR4 could help minimize liver damage in other cases.
This protein could also play a bigger role in alcohol disorders. While it plays an important role in parts of the brain that regulate habits and addiction, mACHR4 is known to exist in lower levels in the brains of patients with alcohol use disorder.
Drugs that boost its levels in the brain are already being tested in clinical trials for schizophrenia, and could eventually be explored as a treatment for alcohol disorders too.
The research was published in the journal Nature.
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