Individuals who fail the breathalyzer test despite reporting no alcohol consumption may be telling the truth. In a recent study published in Nature Microbiology, the findings offer robust biological validation of a syndrome long regarded with skepticism and raise broader questions about the role of microbially derived alcohol in metabolic liver disease, even among individuals who abstain from drinking.

The study examined 22 patients diagnosed with auto-brewery syndrome (ABS), a condition in which endogenous alcohol production occurs in the gut. Using comprehensive metagenomic profiling of the intestinal microbiome, researchers have precisely identified microorganisms and metabolic pathways that can convert the human intestine into an endogenous distillery.

Alcohol Without Drinking

The process is triggered by the ingestion of fermentable carbohydrates, including pasta, bread, sweets, and potatoes. Symptoms of alcohol intoxication typically emerge 2-6 hours after a meal. Affected individuals remain asymptomatic during fasting or on predominantly protein-based diets, a pattern that often adds to diagnostic confusion and fuels mistrust among family members and clinicians.

In a supervised setting without alcohol intake, the participants had a mean blood alcohol concentration of 136 ± 82 mg/dL. Levels were detectable by both serum testing and breathalyzers and were accompanied by clinical signs indistinguishable from those caused by alcoholic beverages.

Although it was first described decades ago in isolated case reports, ABS has remained outside mainstream medicine and is often dismissed as implausible. Patients were frequently labeled as covert drinkers and faced years of diagnostic uncertainty, along with mounting marital, occupational, and legal problems. The lack of structured patient cohorts and rigorous microbiological investigations has kept the condition in a gray area between medical curiosity and scientific legitimacy.

By showing that gut bacteria, rather than fungi as previously assumed, are the main producers of endogenous ethanol, this study reopens the debate on whether microbially derived alcohol may contribute to metabolic dysfunction-associated associated with steatotic liver disease, even in patients who abstain from alcohol consumption.

The True Culprits

Researchers have performed metagenomic analyses of the intestinal microbiome and fecal metabolomics. The participants were matched with healthy individuals from the same household to minimize environmental and dietary confounding factors. Fecal cultures from affected individuals produced a median ethanol concentration of 14.47 mg/dL vs 5.00 mg/dL in healthy individuals from the same household.

The treatment of these cultures with antimicrobials yielded clear results. Chloramphenicol completely abolished ethanol production, whereas amphotericin B had no effect, confirming its bacterial rather than fungal origin. This finding challenges decades of treatment focused on antifungal therapy, based on earlier reports that attributed ABS to Candida overgrowth.

Metagenomic characterization showed increased abundance of Proteobacteria during symptomatic episodes, particularly Escherichia coli and Klebsiella pneumoniae (P < .05), alongside reduced microbial diversity and depletion of butyrate-producing anaerobes such as Ruminococcus bromii and Coprococcus eutactus. Sequencing helped identify several simultaneously active bacterial metabolic pathways, including mixed-acid fermentation, heterolactic fermentation, and ethanolamine utilization. This functional redundancy helps explain why conventional antibiotic treatments often fail as different species can compensate for each other through alternative pathways.

The increased abundance of Proteobacteria alone was not sufficient to produce this syndrome. Cultures from individuals with inflammatory bowel disease, who also showed higher levels of these bacteria, did not show increased ethanol production. Strain-level analysis indicated that individuals with ABS harbor specific E coli variants with greater tolerance to ethanol in culture, suggesting selective enrichment of strains with fermentative capacity distinct from that of commensal variants.

Lessons From China

A 2019 study published in Cell Metabolism was the first to provide strong molecular evidence for this phenomenon. Researchers isolated ethanol-producing strains of K pneumoniae via the 2,3-butanediol fermentation pathway in a Chinese patient with recurrent unexplained intoxication and hepatic steatosis. Although seminal, that report described a single case and focused on one species and its metabolic pathway.

The new study expands this concept by showing that multiple species, including E coli, K pneumoniae, and R gnavus, can contribute simultaneously through at least three distinct metabolic pathways. This functional redundancy explains why organism-specific treatments frequently fail and establishes ABS as a polymicrobial condition rather than a monobacterial condition.

Metabolomic analysis also revealed significantly elevated fecal acetate concentrations in affected individuals, with a strong correlation between acetate levels and blood alcohol levels (P = .63, P < .001). Acetate is a product of ethanol metabolism and is a precursor that can be reconverted to acetyl-CoA before further fermentation, thereby creating a self-sustaining feedback loop.

Diagnosis and Treatment

One of the 22 participants in the study experienced sustained improvement after receiving fecal microbiota transplantation following the failure of standard antibiotic therapy with rifaximin and neomycin. When the initial course did not produce lasting benefits, clinicians used a more intensive approach with vancomycin, metronidazole, and sulfamethoxazole-trimethoprim for 3 days, followed by repeated transplantation of encapsulated donor microbiota with monthly maintenance doses for 6 months. Systemically absorbed antibiotics were chosen to target bacteria in deeper intestinal niches that were not readily reached by non-absorbed agents.

The patient has remained symptom-free for more than 16 months. Metagenomic analysis showed progressive replacement of ethanol-producing bacterial strains with donor-derived strains, and a greater proportion of established donor strains was associated with a lower symptom burden. These observations suggest that successful treatment may depend not only on suppressing pathogenic organisms but also on establishing a more protective gut microbial community. The need for ongoing maintenance therapy indicates that the abnormal microbiome associated with the condition may resist simple eradication and that short courses of antibiotics alone may be insufficient.

The authors recommend that clinicians consider diagnosis in individuals who experience recurrent, unexplained episodes of alcohol intoxication that clearly follow carbohydrate intake. Although ABS is rare, a history of broad-spectrum antibiotic exposure is common among documented cases, and gastrointestinal conditions such as short bowel syndrome, Crohn’s disease, and dysmotility may increase the risk for the condition.

The diagnosis was based on carbohydrate challenge testing performed under medical supervision. Participants received 75-100 g of oral glucose, and blood alcohol levels were measured at baseline and 2, 4, and 6 hours. Median peak levels were observed at approximately 240 minutes, indicating that testing protocols that end earlier may fail to capture delayed ethanol production. Clinical observation of intoxication and laboratory findings supported the diagnosis.

Patient management was performed in a stepwise manner. Limiting fermentable carbohydrates is central to symptom control and, in some cases, is sufficient to maintain remission. When antimicrobial therapy was used, the treatment targeted bacterial contributors to ethanol production rather than the antifungal strategies that had been emphasized in earlier reports. In refractory cases, fecal microbiota transplantation has been described as a therapeutic option, particularly when combined with targeted antibiotic therapy and prolonged follow-up.

Although ABS is rare, this study suggests that the underlying microbial mechanisms may have broader implications in understanding how gut microbial metabolism can lead to systemic intoxication without alcohol consumption.

A 2019 study identified that transplanting high alcohol-producing strains in animal models caused features of fatty liver, including steatosis and liver injury. This provides evidence that microbial ethanol production in the gut contributes to liver pathology. The identification of multiple bacterial pathways capable of sustained ethanol production supports the plausibility that chronic low-level endogenous alcohol generation, even when insufficient to cause clinically evident intoxication, may contribute over time to the development of metabolic dysfunction-associated associated with steatotic liver disease.

Accordingly, in patients with atypical progression of steatohepatitis or liver injury that is disproportionate to metabolic risk factors, particularly those with a history of dysbiosis or extensive antibiotic exposure, microbial investigations should be considered. For rare individuals who test positive on a breathalyzer despite not having consumed alcohol, science now offers not only a plausible scientific explanation but also objective diagnostic tools and effective treatment options.

Obede Junior is a journalist with more than 20 years of experience in communication and has contributed to the Terra and UOL portals.

This story was translated from Medscape’s Portuguese edition.