San Diego Researchers Find Fungi Link To Liver Disease

SAN DIEGO COUNTY, CA – Controlling the amount and type of fungi in the intestines could prove to be a key to treating alcohol-related liver disease, scientists at the UC San Diego School of Medicine and J. Craig Venter Institute of La Jolla reported Monday.

The researchers found multiple connections between fungi and liver disease in both mice and people in a study published in Monday's edition of the Journal of Clinical Investigation.

Most scientific knowledge about alcoholic liver disease previously focused on bacteria.

"Not only is this the first study to associate fungi and liver disease, we might be able to slow the progression of alcoholic liver disease by manipulating the balance of fungal species living in a patient's intestine," said Dr. Bernd Schnabl, an associate professor of gastroenterology at UCSD.

Schnabl and his colleagues found that the antifungal compound amphotericin B protected mice from alcohol-induced liver disease.

The scientists also compared fungi in the stool of eight healthy people and 20 people with chronic alcohol abuse and various stages of liver disease.

They found that the healthy people had a richer diversity of fungi living in their intestines, as compared to alcohol-dependent patients, who at all stages of liver disease had dramatic overgrowths of one fungal type in particular -- Candida, which includes the species that causes yeast infections.

Further, they discovered a correlation between fungi and disease severity in a separate group of 27 patients with alcohol-related liver disease. The higher the exposure to fungi, as measured by a person's level of antibodies that recognize them, the higher the risk of death.

Fourteen patients had high fungi levels and 13 were low. After five years, 77 percent of the low-fungi group survived, compared to 36 percent of the high-fungi group.

Schnabl pointed out that the number of study subjects was small, so more study is needed.

However, study co-author Derrick Fouts, a professor of genomic medicine at the Venter institute, said the findings suggest that fungi have a greater role in "modulating the human microbiome" than was previously appreciated.

According to the scientists, liver cirrhosis is the 12th leading cause of death worldwide, with about half due to alcohol abuse. There are no specific treatments, other than abstaining from alcohol use.

The researchers found that fungi flourished in the intestines of mice with chronic alcohol exposure and, in turn, the fungal overgrowth exacerbated liver disease.

Parts of the fungal cell wall, mainly a sugar called beta-glucan, moved through a mouse's intestinal wall into the surrounding body cavity and organs. Once relocated inside the liver, beta-glucan bound certain immune cells and triggered inflammation. Chronic inflammation kills liver cells and ultimately promotes alcoholic liver disease.

Mice were given amphotericin B orally, but oral ingestion has not been approved for human use. Intravenous use for humans is available for treating serious fungal infections, but can result in side effects, according to UCSD.

Scientists affiliated with the Veterans Affairs San Diego Healthcare System, and hospitals and universities in Belgium, Canada, China, Germany, Japan and Taiwan also contributed to the study.

The study's funders included the National Institutes of Health, Biomedical Laboratory Research & Development Service of the Veterans Affairs Office of Research and Development, the German Research Foundation, Swiss National Science Foundation and Wellcome Trust of London.

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