Gut Bacteria Tied to Rare Disease That Makes People Drunk Without Drinking

Imagine getting intoxicated without drinking a drop of alcohol. This is what happens in people with auto-brewery syndrome (ABS), where microbes in the gut produce alcohol that then becomes absorbed into the blood stream at high levels.

It's a rare condition, and for those with ABS, getting a diagnosis can be difficult. There are multiple medical visits, doctors that don't believe the condition is real, and a lengthy test that involves drinking glucose and seeing what happens to blood alcohol levels hours later. “Most of the published literature right now are really case reports,” said Bernd Schnabl, a physician scientist at the University of California, San Diego.

Schnabl coauthored a paper that was recently published in Nature Microbiology documenting the largest study to date on ABS, which included 22 patients with ABS compared to 21 unaffected household partners as controls.¹ The scale of the study helped solidify the role of specific bacteria and their metabolic pathways in ABS, providing a way forward for exploring treatment options.

“This is a very landmark paper for auto-brewery syndrome,” said Ahmed Bayoumy, a physician researcher at Amsterdam University Medical Center who was not involved in the study. “They've really collected a bigger cohort, and they did a very comprehensive analysis.”

Schnabl began working on ABS in 2019 when Jing Yuan, a researcher at Capital Institute of Pediatrics who studied the condition, contacted him. Yuan had noticed that Klebsiella pneumoniae levels fluctuated in a patient with ABS: Alcohol levels increased when the bacteria levels were high, and when the patient wasn't intoxicated, bacteria levels were low.² Through this connection, Schnabl began working with Barbara Cordell, who runs an ABS support group on Facebook and is a study coauthor. The team recruited their cohort from the support group and collected stool, blood, and clinical information to get a deeper understanding of the disease.

Stool samples from patients with ABS had higher amounts of certain bacterial species, particularly Escherichia coli and K. pneumoniae, and had significantly more metabolic pathways involved in alcohol fermentation represented in their genomes. When researchers placed stool samples into bacterial growth media, they found that the samples taken during an ABS flare produced more alcohol compared to stool from household members or from patients during remission.

Danny De Looze, a gastroenterologist at University Hospital of Ghent who was not involved in the study, said that “These authors have done a great job…in really showing that it’s certain groups of bacteria that produce alcohol.”

The researchers did not find any significant differences in terms of fungal composition from the stool samples in patients with ABS versus household partners. "That was something surprising," said Schnabl, as many case reports in the past had mentioned that yeast or fungi might be involved.³ Yet, Schnabl doesn't "want to rule out" the possibility that yeast and fungi could play a role in some cases of ABS.

The differences in the bacterial composition between those with ABS and controls hinted at the possibility that fecal microbiota transplants (FMT) could treat ABS. To mitigate symptoms, most patients with ABS are on low carbohydrate diets and have tried antibiotics, antifungals, prebiotics, and postbiotics, said Schnabl. A few case studies—including one reported by De Looze—found that FMTs can help.⁴ However, some patients relapse and must deal with the condition long term.

In search of a solution, one patient in the cohort reached out to Elizabeth Hohmann, a clinical researcher at Massachusetts General Hospital and a coauthor on the study, and connected her to Schnabl. This spurred a collaboration to try FMT in the patient. After the first FMT treatment, the patient showed improved symptoms without detectable blood alcohol levels for three months, but the symptoms came back. The researchers initiated another FMT nine months after the first treatment, which included an antibacterial pretreatment and monthly maintenance doses of FMT for six months. This patient remained in remission for over 16 months during their study.

The researchers now have a Phase 1 clinical trial underway to evaluate FMTs to treat ABS. “The exciting thing was because of this pilot patient's results, we were able to get an NIH grant…to study eight patients,” said Hohmann. “In that trial, one of the things we're doing is studying the microbiome over time in the new patients.”