Gut microbial ethanol metabolism contributes to auto-brewery syndrome in an observational cohort.

Faecal samples from ABS patients during a flare produced significantly more ethanol in vitro compared to unaffected household partners.

• The observational cohort included 22 patients with ABS and 21 unaffected household partners
• In vitro ethanol production from faecal samples was elevated during ABS flares
• Antibiotic treatment reduced in vitro ethanol production from ABS faecal samples
• Household partners were used as controls to minimize confounding by shared environmental and dietary factors

Gut microbiome metagenomic analysis revealed an enrichment of Proteobacteria in ABS patients, including Escherichia coli and Klebsiella pneumoniae.

• Metagenomics was used to characterize the gut microbiome of ABS patients versus household partner controls
• Proteobacteria were specifically enriched in the ABS cohort
• Both Escherichia coli and Klebsiella pneumoniae were identified as enriched species in ABS patients
• These are known ethanol-producing bacterial species capable of fermentation

Genes in multiple ethanol-production metabolic pathways were enriched in ABS patients.

• The mixed-acid fermentation pathway showed gene enrichment in ABS patients
• The heterolactic fermentation pathway showed gene enrichment in ABS patients
• The ethanolamine utilization pathway showed gene enrichment in ABS patients
• These pathway-level findings were identified through metagenomic functional analysis

Faecal metabolomics revealed increased acetate levels in ABS patients that correlated with blood alcohol concentrations.

• Faecal metabolomics was performed to characterize metabolic differences between ABS patients and controls
• Acetate levels were specifically elevated in ABS patients
• Increased acetate levels correlated with blood alcohol concentrations in ABS patients
• This association suggests acetate as a potential biomarker or mechanistic contributor to ABS

One ABS patient treated with faecal microbiota transplantation (FMT) showed positive correlations between gut microbiota composition and function, and symptoms.

• A single patient case of FMT treatment was reported within the observational cohort
• Positive correlations were observed between changes in gut microbiota composition and ABS symptoms following FMT
• Positive correlations were also observed between gut microbiota function and ABS symptoms following FMT
• This case provides preliminary evidence that gut microbiota modulation may be a viable therapeutic approach for ABS

ABS is a rarely diagnosed disorder of alcohol intoxication due to gut microbial ethanol production, with previously poorly understood microbiological profiles.

• Prior to this study, knowledge of ABS microbiological profiles was limited to case reports and a small cohort study
• The current study represents an observational cohort of 22 ABS patients, larger than prior cohort work
• ABS involves endogenous ethanol production by gut microbes leading to intoxication
• The study design used unaffected household partners as controls to reduce environmental confounding