Gut fungus shapes alcohol preference opening doors to new treatments

New research has found a connection between a human-resident fungus, Candida albicans, and the brain’s dopamine reward pathway, influencing alcohol preference. 

The publication in mBio observed that an overgrowth of this fungus in mice resulted in increased prostaglandin E2 (PGE2). These inflammatory molecules can cross the blood-brain barrier and change the desire for alcohol. 

PGE2 changes dopamine signaling in the dorsal striatum part of the brain, where habit formation and reward processing occur, the researchers explain. The multifunctional molecule also mediates several inflammatory responses, such as reducing stomach acid or triggering fevers.

Next to influencing cravings for alcohol, high levels of C. albicans in the gut are linked to poor diet and antibiotic use, which facilitates PGE2 production.

Surprising finding

Researchers at Tufts University School of Medicine and Graduate School of Biomedical Sciences, US, hypothesized that mice guts colonized with C. albicans would find alcohol more rewarding, but their findings revealed the opposite.

“Our study shows how science works — our initial ideas were very wrong,” says first author Andrew Day, who conducted the study while he was a Ph.D. student.

“This could be explained by differences in how mice respond to C. albicans compared to humans, differences in fungal strains, or we might be seeing a small snapshot of the entire story.”

In the study, the mice were seen to avoid alcohol as PGE2 levels rose along with the fungal populations. When the PGE2 receptor molecules were blocked, their behavior reversed. 

Mice with C. albicans overgrowth were noted to be more sensitive to alcohol’s effects on motor coordination. However, researchers say this can be reversed by blocking PGE2 activity.

Alternative approaches needed

The study underlines that alcohol use disorder impacts over 5% of adults globally, disrupting their ability to stop drinking despite the negative consequences. 

Traditional treatments include behavioral therapy, support groups, medications, and maintaining abstinence, but they are only moderately effective, the researchers point out. Some people have high relapse rates, highlighting a need for alternative approaches.

Senior author Carol Kumamoto, a professor of molecular biology and microbiology at the School of Medicine, adds: “Our bodies are wired so that our behavior responds to gut microbiota, and this study highlights that fungi are important components of the gut-brain axis.”

“We think fungal colonization levels in individuals with alcohol use disorder could be impacting host alcohol consumption by influencing interest in drinking — whether it’s affecting how rewarding a drink may be is more of an interpretation.”

The researchers add that recent clinical trials using fecal microbiota transplants show promising effects on alcohol preference and consumption.

Among other recent studies, a review spotlighted the mycobiota, the often-overlooked part of the gut microbiome made of various fungi. It plays a crucial role in shaping immunity and affecting health and disease. 

Other research finds evidence of a previously unknown three-way relationship between human genetics, the gut mycobiome, and the risks of developing chronic diseases.