Heavy drinking can lead to liver disease, but a new study suggests that it's not just the alcohol that damages the liver — fungi that commonly live in the human gut appear to contribute to the disease as well.
The study, which involved experiments in both mice and a small number of people, found that consuming alcohol is linked with changes in the types of fungi living in the gut and that the fungi that tend to be more common in people who drink also worsen the effects of alcohol on the liver. The study is the first to link fungi and liver disease, the researchers said.
What's more, the findings suggest that antifungal drugs may be a possible treatment for alcohol-related liver disease, the researchers said. Alcohol-related liver disease is a category that includes a range of diseases, from the less severe "fatty liver" disease to end-stage liver disease, also called cirrhosis.
The findings suggest that "we might be able to slow the progression of the alcoholic liver disease by manipulating the balance of fungal species living in a patient's intestine," study co-author Dr. Bernd Schnabl, an associate professor of gastroenterology at the University of California, San Diego School of Medicine, said in a statement.
Previous studies had found a link between excessive drinking and imbalances of bacteria in the gut, but until now, few studies had looked at the role of gut fungi in the development of alcohol-related diseases. In the new study, the researchers gave alcohol to mice daily for eight weeks and found that this chronic alcohol exposure resulted in an overgrowth of certain types of fungi in the animals' intestines.
But if the researchers treated the mice with the antifungal drug amphotericin B, this decreased levels of fungi while also reducing the severity of alcoholic liver disease in the animals. Mice that received the antifungal drug had lower levels of liver damage and fat accumulation in the liver, compared with mice that did not receive the drug, the researchers said.
The researchers' experiments showed that fungi contribute to alcoholic liver disease in the following way: The fungi release a sugar called beta-glucan and this sugar moves out of the intestine and into surrounding organs, including the liver. When it gets to the liver, beta-glucan can trigger an inflammatory response that kills liver cells and promotes alcoholic liver disease, the researchers said. Thus, heavy drinking boosts the level of fungi in the gut, and this, in turn, leads to an increase in levels of beta-glucan, which promote more inflammation in the liver.
The researchers also examined fungi in the stool of eight healthy people and in 20 people who had abused alcohol and were in various stages of liver disease. They found that the alcohol-dependent people had a dramatic overgrowth of a type of fungus called Candida in their guts.
Next, the researchers analyzed blood samples from a separate group of about 30 patients with the alcoholic liver disease, and they measured levels of antibodies that recognize fungus. They found that the people with higher levels of these antibodies — which indicate greater exposure to intestinal fungus — were more likely to die from liver disease over a five-year period.
The researchers cautioned that their studies focused on only a small number of people, and so larger studies are needed to confirm the findings. In addition, future studies should look at whether a single fungus contributes more than others to the progression of liver disease.
The researchers are now interested in testing amphotericin B in patients with alcohol-related liver disease to see if the drug helps with the condition.
The study was published May 22 in the Journal of Clinical InvestigationOriginal article on Live Science.
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