Researchers Search for Why Some People’s Gut Microbes Produce High Alcohol Levels

Researchers have identified specific gut bacteria and metabolic pathways that drive alcohol production in patients with auto-brewery syndrome (ABS), a rare and often misunderstood condition in which people experience intoxication without drinking alcohol. The research team from Mass General Brigham, in collaboration with colleagues at University of California San Diego, published their findings in Nature Microbiology.

ABS occurs when gut microbes break down carbohydrates and convert them to ethanol (alcohol) that enters the bloodstream. While carbohydrate metabolism can produce small amounts of alcohol in everyone, levels can be high enough to cause intoxication in people with ABS. The condition is extremely rare but likely underdiagnosed due to a lack of awareness, diagnostic challenges, and stigma.

Many patients experience years of misdiagnosis and social, medical, and legal consequences before receiving a diagnosis. Confirmation of ABS is also difficult to obtain, as the gold-standard diagnosis requires monitored blood alcohol testing under supervised conditions.

To better understand the condition, researchers evaluated 22 patients with ABS, 21 unaffected household partners, and 22 healthy control participants. The team then compared gut microbial composition and function across groups.

The study showed that stool samples taken from patients during a flare of ABS produced significantly more ethanol in the lab than samples from household partners or healthy controls—pointing to the potential for a stool-based diagnostic test.

Previously, scientists had very little information about which specific gut microbes (yeasts or bacteria) caused ABS. The stool analysis pointed to several bacterial species as key drivers in patients including Escherichia coli and Klebsiella pneumoniae. In addition, during ABS flares, some patients had much higher levels of enzymes involved in fermentation pathways, compared to controls. While some patients had these organisms, the authors note that finding the causative microbes in individual patients is an arduous process.

Researchers also followed one patient who experienced symptom relief after undergoing a fecal microbiota transplantation when other treatments had failed. Relapse and remission corresponded with shifts in specific bacterial strains and metabolic pathway activity, providing further biological evidence for the condition. After a second fecal transplant, with different antibiotic pretreatment, the patient was symptom-free for more than 16 months.

“Auto-brewery syndrome is a misunderstood condition with few tests and treatments. Our study demonstrates the potential for fecal transplantation,” said co-senior author Elizabeth Hohmann, MD, of the Infectious Disease Division in the Mass General Brigham Department of Medicine. “More broadly, by determining the specific bacteria and microbial pathways responsible, our findings may lead the way toward easier diagnosis, better treatments, and an improved quality of life for individuals living with this rare condition.”

Hohmann is currently working with colleagues at UC San Diego on a study evaluating fecal transplantation in eight patients with ABS.

Authorship: In addition to Hohmann, Mass General Brigham authors include Valeria Magallan. Additional authors include Cynthia L. Hsu, Shikha Shukla, Linton Freund, Annie C. Chou, Yongqiang Yang, Ryan Bruellman, Fernanda Raya Tonetti, Noemí Cabré, Susan Mayo, Hyun Gyu Lim, Barbara J. Cordell, Sonja Lang, Peter Stärkel, Cristina Llorente, Bernhard O. Palsson, Chitra Mandyam, Brigid S. Boland, Elizabeth Hohmann, and Bernd Schnabl.

Disclosures: Schnabl has been consulting for Ambys Medicines, Boehringer Ingelheim, Ferring Research Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals, Surrozen and Takeda. Schnabl’s institution UC San Diego has received research support from Axial Biotherapeutics, BiomX, CymaBay Therapeutics, Intercept, NGM Biopharmaceuticals, Prodigy Biotech and Synlogic Operating Company. Schnabel is founder of Nterica Bio. Hohman has received research support from Seres Therapeutics, MicrobiomeX/Tend.

Funding: This work was supported by the National Institutes of Health (grants K99 AA031328 and T32 DK007202), the American Association for the Study of Liver Diseases Foundation (Grant #CTORA23-208366), and a Pilot and Feasibility Award from the Southern California Research Center for ALPD and Cirrhosis funded by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health P50AA011999 (to C.L.H), in part by NIH grants R01 AA024726, R01 AA020703, U01 AA026939, by Award Number BX004594 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (to B.S.) and services provided by NIH centers P50 AA011999 and the San Diego Digestive Diseases Research Center (SDDRC) P30 DK120515. This study was supported in part by NIH grants R01 AA029106, 1R21 AA030654, P30 AR073761 the D34 HP31027 UC San Diego’s Hispanic Center of Excellence, and by the Isenberg Endowed Fellowship jointly awarded by the Pilot/Feasibility Program of the San Diego Digestive Diseases Research Center (SDDRC), the Hellman Family Foundation (P30 DK120515) (to C.L.). This work was also supported by the Joint BioEnergy Institute, U.S. Department of Energy, Office of Science, Biological and Environmental Research Program under Award Number DE-AC02-05CH11231. This publication includes data generated at the UC San Diego IGM Genomics Center utilizing an Illumina NovaSeq X Plus that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929).

Paper cited: Hsu CL et al. “Gut microbial ethanol metabolism contributes to auto-brewery syndrome in an observational cohort” Nature Microbiology DOI: 10.1038/s41564-025-02225-y