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Intestinal fungi contributes to the development of alcoholic liver disease (2017-05-24)

A new study funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) is among the first to suggest that intestinal fungi (or mycobiota) may contribute to the development of alcoholic liver disease (ALD).

ALD encompasses a broad range of liver diseases, from simple steatosis (fatty liver) to end-stage liver disease, or cirrhosis (liver cell death).

Researchers at the University of California, San Diego and the J. Craig Venter Institute in Rockville, Maryland, demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal ▀-glucan into systemic circulation in mice.

Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased ▀-glucan translocation, and ameliorated ethanol-induced liver disease.

ALD has previously been associated with bacterial overgrowth in the intestines, as well as a shift in the types of bacteria found there.
Until now, little was known about the role of intestinal fungi in ALD.

In the current study, the researchers found that fungi flourished in the intestines of mice with chronic alcohol exposure.

In turn, they noted that fungal overgrowth exacerbated alcohol-induced liver disease.

To determine whether preventing intestinal overgrowth protected mice from alcohol-induced liver disease, the researchers treated them with the antifungal agent amphotericin B.

They observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth.

Compared with healthy individuals and patients with nonľalcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota.

Compared to untreated mice, mice with alcohol-related liver disease that received a form of amphotericin B had lower levels of fat accumulation, reduced intestinal fungal overgrowth, decreased ▀-glucan translocation, and ameliorated ethanol-induced liver disease.

The researchers also conducted small preliminary studies with humans to examine intestinal fungi of people with alcohol use disorder and various stages of liver disease.

They also found that the more prevalent the fungal overgrowth in individuals with ALD, the higher the likelihood of mortality.

Taken together, this research suggests that fungi may play a greater role than previously understood in controlling the diverse array of microbes that live on and inside the human body.

If further study confirms that fungi are involved in the worsening of ALD, it may be possible to slow disease progression by adjusting the balance of fungal species living in the intestine of a person with ALD.

For more information
The Journal of Clinical Investigation
Intestinal Fungi Contribute to Development of Alcoholic Liver Disease