Summary: A new study reveals that an overgrowth of Candida albicans, a common gut fungus, may alter the brain\u2019s dopamine reward circuitry and influence alcohol consumption. Researchers found that as fungal populations increased, they triggered production of inflammatory molecules called PGE2, which crossed into the brain and changed dopamine signaling in the dorsal striatum.<\/p>\n
Unexpectedly, mice with high fungal levels began avoiding alcohol, but when PGE2 activity was blocked, they resumed drinking. The findings highlight the surprising role of fungi in the gut-brain axis and open new avenues for treating alcohol use disorder.<\/p>\n
Key Facts:<\/p>\n
Fungal-Brain Link: Overgrowth of Candida albicans raised PGE2 levels that affected dopamine pathways tied to alcohol reward.Reversible Effect: Blocking PGE2 receptors restored alcohol preference in mice, showing a direct gut-to-brain mechanism.Therapeutic Potential: Understanding fungal influence on dopamine signaling could lead to new strategies for alcohol use disorder.<\/p>\n
Source: Tufts University<\/p>\n
Researchers at\u00a0Tufts University School of Medicine\u00a0and\u00a0Tufts Graduate School of Biomedical Sciences\u00a0have found a surprising connection between a fungus associated with alcohol use disorder and the brain\u2019s dopamine reward pathway. <\/p>\n
Published October 16 in the journal\u00a0mBio, the\u00a0study\u00a0describes, in mice, how an overgrowth of\u00a0Candida albicans\u2014a fungus that naturally resides in the human gut\u2014increases levels of inflammatory molecules called PGE2\u00a0that can cross the blood-brain barrier and affect the desire for alcohol.<\/p>\n
PGE2, short for prostaglandin E2, is a multifunctional molecule involved in mediating inflammatory responses, reducing stomach acid, or triggering fevers. As\u00a0C. albicans\u00a0blooms in the gut\u2014which is associated with antibiotic use, poor diet, or alcohol consumption\u2014it both produces and stimulates the production of PGE2.<\/p>\n
The study suggests that as the molecules circulate, they enter the forebrain and alter dopamine signaling in the dorsal striatum, a region involved in reward processing and habit formation.<\/p>\n
While the researchers hypothesized that mice would find the taste of alcohol more rewarding and thus drink more when colonized with\u00a0C. albicans, the results showed the opposite.<\/p>\n
As PGE2\u00a0levels rose along with fungal populations, the mice began to avoid the beverage. When the investigators blocked PGE2\u00a0receptor molecules, the behavior was reversed, and the mice would drink alcohol again.<\/p>\n
\u201cOur study shows how science works\u2014our initial ideas were very wrong,\u201d said first author Andrew Day, who conducted the study while a Ph.D. student in the\u00a0Molecular Microbiology\u00a0program at the Graduate School of Biomedical Sciences.<\/p>\n
\u201cThis could be explained by differences in how mice respond to\u00a0C. albicans\u00a0compared to humans, differences in fungal strains, or we might be seeing a small snapshot of the entire story.\u201d<\/p>\n
The researchers also discovered that mice with\u00a0C. albicans\u00a0overgrowth were more sensitive to alcohol\u2019s effects on motor coordination. This effect could also be reversed by blocking PGE2\u00a0activity.<\/p>\n
\u201cOur 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,\u201d said senior author\u00a0Carol Kumamoto, a professor of molecular biology and microbiology at the School of Medicine.<\/p>\n
\u201cWe think fungal colonization levels in individuals with alcohol use disorder could be impacting host alcohol consumption by influencing interest in drinking\u2014whether it\u2019s affecting how rewarding a drink may be is more of an interpretation.\u201d<\/p>\n
Alcohol use disorder affects over 5% of adults worldwide and is defined by an inability to control or stop alcohol consumption despite negative consequences. Traditional treatments\u2014including behavioral therapy, support groups, medications, and maintaining abstinence\u2014are only moderately effective, with some adults experiencing high relapse rates, creating a need for alternative approaches.<\/p>\n
Future studies into the impact of fungi and PGE2\u00a0on alcohol use disorder could reveal new contributors to its progression. Recent clinical trials have investigated fecal microbiota transplants for the disorder, with preliminary studies showing promising effects on alcohol preference and consumption.<\/p>\n
Additional authors are\u00a0Jamie Maguire, professor at the School of Medicine, and research technician Emma Hayes of Tufts University School of Medicine;\u00a0Katrina Blandino, a Ph.D. student at the Graduate School of Biomedical Sciences; Alyssa DiLeo, a graduate of the Graduate School of Biomedical Sciences; and Jeyra Perez-Lozada, formerly of Tufts University School of Medicine.<\/p>\n
Funding:<\/p>\n
Research reported in this article was supported by the National Institutes of Health\u2019s National Institute of Allergy and Infectious Diseases (under award numbers T32AI007422 and R01AI118898) and National Institute on Alcohol Abuse and Alcoholism (under award number R01AA026256), and by the Tufts Initiative on Substance Use and Addiction. Complete information on authors, funders, methodology, limitations, and conflicts of interest is available in the published paper.\u00a0<\/p>\n
The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.<\/p>\n
Key Questions Answered:Q: What does the fungus Candida albicans have to do with alcohol use?<\/p>\n
A: Overgrowth of this gut fungus increases levels of the inflammatory molecule PGE2, which can travel to the brain and alter dopamine signaling linked to alcohol reward.<\/p>\n
Q: What did researchers find about alcohol consumption in mice?<\/p>\n
A: Surprisingly, mice with high C. albicans levels drank less alcohol. When scientists blocked PGE2 signaling, the mice began drinking again.<\/p>\n
Q: Why does this matter for people with alcohol use disorder?<\/p>\n
A: The findings suggest that fungal imbalances in the gut may affect how rewarding alcohol feels, offering a new biological target for treatment.<\/p>\n
About this AUD and neuroscience research news<\/p>\n
Author: Rhonda Siciliano<\/a>
Source: Tufts University<\/a>
Contact: Rhonda Siciliano \u2013 Tufts University
Image: The image is credited to Neuroscience News<\/p>\n