Doctors discover the source of mysterious intoxication

Scientists have identified specific gut bacteria and biological pathways that cause alcohol to be produced inside the body in people with auto-brewery syndrome (ABS). This rare and frequently misunderstood condition causes individuals to experience intoxication even though they have not consumed alcohol. The research was conducted by a team at Mass General Brigham in collaboration with researchers from the University of California San Diego and was published on January 7 in Nature Microbiology.

Auto-brewery syndrome develops when certain microbes in the gut break down carbohydrates and convert them into ethanol (alcohol), which then enters the bloodstream. While normal digestion can create trace amounts of alcohol in anyone, people with ABS can produce levels high enough to cause noticeable intoxication. Although the condition is extremely rare, experts believe it is often missed because of limited awareness, difficulties with diagnosis, and social stigma.

Many people with ABS spend years without an accurate diagnosis. During that time, they may face social strain, medical complications, and even legal problems linked to unexplained intoxication. Confirming the condition is also challenging because the gold-standard diagnostic approach requires carefully supervised blood alcohol testing, which is not easily accessible in many settings.

To investigate the biological roots of the disorder, researchers studied 22 people diagnosed with ABS, along with 21 unaffected household partners and 22 healthy control participants. The team compared the makeup and activity of gut microbes across these groups to identify meaningful differences.

Laboratory testing showed that stool samples collected from patients during active ABS flare-ups produced far more ethanol than samples from household partners or healthy controls. This finding highlights the possibility of developing a stool-based test that could make diagnosing the condition easier and more reliable in the future.

Until now, scientists had limited information about which specific gut microbes (yeasts or bacteria) were responsible for auto-brewery syndrome. Detailed stool analysis pointed to several bacterial species as key contributors, including Escherichia coli and Klebsiella pneumoniae. During symptom flare-ups, some patients also showed much higher levels of enzymes involved in fermentation pathways compared to control participants. The researchers note that identifying the exact causative microbes in individual patients remains a complex and time-consuming task.

The research team also followed one patient whose symptoms improved after receiving a fecal microbiota transplantation when other treatments had not worked. Periods of relapse and recovery closely matched changes in specific bacterial strains and metabolic activity in the gut, offering additional biological evidence for the condition. After a second fecal transplant, using a different antibiotic pretreatment, the patient remained 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).