Friday, March 14, 2025
3/14/2025
ABSTRACT Auto brewery syndrome (ABS), also known as gut fermentation syndrome, is a rare condition in which a dysfunctional intestinal microbiome produces ethanol, which is absorbed and results in intoxication. ABS may result in behavioral, familial, social, and legal problems and is difficult to diagnose in part because of its rarity, and because alcohol use disorder is common. Patients typically have “flares” of the condition, with episodes of inebriation. ABS may be caused by yeast, sometimes brewer’s yeast or Saccharomyces cerevisiae, but it may also be associated with bacteria, such as Klebsiella species, E. coli or others, sometimes in combination. We recruited 38 ABS patients and their household partners (HHP). Preliminary data showed that anaerobic bioreactor cultures of ABS patient microbiota produced ex vivo significantly more ethanol than that of HHP. Ethanol production was abrogated by antibiotic treatment. Metagenomic analysis of fecal samples showed higher proportions of several bacterial species and of genomic DNA encoding alcohol dehydrogenase (ADH) in stool of patients with ABS as compared with HHP. These findings indicate that pathologic production of ethanol is driven by gut bacteria in most ABS patients. We have safely treated one ABS patient with an active flare using capsule fecal microbiota transplantation (FMT) under a single patient treatment IND. The patient achieved clinical remission. We hypothesize that FMT in ABS patients is safe, tolerable and may result in an eradication of alcohol producing microbes. We therefore propose a phase 1, open label safety and feasibility study of capsule-based FMT in subjects with ABS under FDA and IRB supervision. Primary clinical outcomes are safety and feasibility; secondary and exploratory endpoints include clinical outcomes and assessment of flares by blood and breathalyzer ethanol monitoring, dietary intake, and microbiome and bioreactor assessment of stool samples. These studies may reveal a new and safe therapeutic approach for patients with ABS, and will improve our understanding of how gut microbial ethanol production contributes to the disease. Results from this safety and tolerability study may lead to the conduct of a larger randomized controlled clinical trial for FMT use in patients with ABS. The study may also inform our understanding of the effect of the microbiome on other hepatic and metabolic disorders.
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