Factors in an Auto-Brewery Syndrome group compared to an American Gut Project group: a case-control study

Introduction

Auto-Brewery Syndrome (ABS), also known as Gut Fermentation Syndrome and ‘endogenous ethanol fermentation’, is a rare but underdiagnosed syndrome¹. An overgrowth of fermenting yeast or bacteria in the intestines causes patients to ferment carbohydrates and sugars into ethanol. Patients test positive for blood alcohol, often at very high levels, without ingesting alcohol but may or may not exhibit signs and symptoms of intoxication.

The earliest cases were reported in France in 1894 and translated from French into English in 1906 in the book Auto-Intoxication in Disease². Since then, at least 68 case studies in Japan, Canada, the United States, Italy, and other countries were published in the post-1950s academic literature³. Of those, 14 individual cases have been published in the last decade and the disease is finally starting to be recognized as a rare but treatable syndrome⁴.

We observe that ABS is often reported in people with co-morbidities, such as gastroparesis, Crohn’s disease, short bowel syndrome, and obesity-related liver disease^5,6 but otherwise-healthy people are being diagnosed as well^7,8. While numerous case studies describe the diagnosis and treatment, little is known about the factors that cause or even contribute to ABS.

The scores of published cases of ABS, with two exceptions, all point to an over-colonization of fermenting yeast in the gastrointestinal tract. The first anomaly is the case of a man in China with severe non-alcoholic steatohepatitis and bacterial ABS⁹. Strains of a high alcohol-producing Klebsiella pneumoniae (HiAlc KPN) were strongly associated with his endogenous production of alcohol. With further research, the HiAlc KPN was associated with 60% of people with non-alcoholic fatty liver disease (NAFLD) in a cohort of Chinese people. Furthermore, isolates of the microbes transferred from the subjects to healthy mice induced NAFLD. The second deviation from the norm is a case study published with the location of the fermenting yeast, Candida glabrata, in the patient’s urinary system¹⁰. The authors demonstrated high levels of ethanol production in the patient’s urine that was confirmed with an in vitro experiment.

Of the thousands of different species of microbes in an individual’s gut, an estimate of less than 0.1% are considered rare, and fungi belong to the rare biosphere known as the mycobiome. Most of the reports of fungal infections focus on yeast and fungal overgrowth in immunocompromised patients but the incidence of fungemia is increasing. Symptoms of yeast overgrowth include fatigue, headaches, poor concentration, gastrointestinal distress, muscle pain, joint pain, and urogenital symptoms¹¹.

We now know that underlying genetic susceptibility to Candida plays an important role in infections. Normally, natural defense mechanisms prevent the commensal Candida and other yeasts from becoming pathogenic. But loss of barrier function, imbalances in the gut microbiome, or inadequate immunity may lead to increased susceptibility to invasive candidiasis¹².

In addition to the universally demonstrated overgrowth of fermenting yeast or bacteria, patients with ABS often have signs of yeast infections in their integumentary, genitourinary, or oral systems. Some patients with ABS respond to dietary changes alone, while others require anti-fungal medication, dietary changes, supplements, probiotics, and lifestyle modifications such as adequate sleep, stress-reduction, and moderate exercise. A small number of patients do not seem to respond to any of the mentioned treatments or will persistently relapse. For these chronic patients, a Fecal Microbiota Transplant (FMT) appears to be a promising treatment. A patient in Belgium received what we believe is the first published case of a successful FMT for ABS¹³.

Of four previous studies on groups of fermenting patients, only one looked at ABS patients’ demographics, health history, lifestyle factors, and diet to determine factors that might contribute to ABS¹⁴. The study demonstrates that patients with ABS or symptoms have significant differences in their lifestyle and health, diet, and past medical history compared to household participants who live with someone with ABS but do not have clinical ABS.

The purpose of the current research project is to identify the health history and lifestyle factors of subjects diagnosed with ABS and their household members and compare those factors in subjects of a large control group from the database of the American Gut Project (AGP). The AGP is a crowd-funded science project to analyze the gut microbiomes of a large cross section of American citizens and determine what health and lifestyle factors correlate to different microbiomes¹⁵. The null hypothesis is that there will be no differences between the ABS and household members compared to the AGP group on thirty questions related to health and lifestyle.

Methods

Results

Discussion

Using the 30 identical questions from the Gut Fermentation Survey and AGP survey, we found 12 statistically significant differences between people with ABS or living with someone with ABS and the more general group of persons participating in the AGP.

In the Lifestyle and Health section, the fact that people in the ABS group are more likely to have a lesser quality of bowel movements than the large data set (N=11,297) from the AGP, supports the idea that gut dysbiosis is the underlying cause of ABS. This a similar finding to previous research we conducted and strengthens the finding¹⁴. People with perturbations in the gut microbiota would be expected to have changes in bowel habits and conversely changes in bowel habits reflect gut dysbiosis. There is evidence that changing the gut microbiota through fecal transplant, often relieves symptoms such as diarrhea, indigestion, and abdominal pain²².

The strongly significant difference that subjects in the ABS group get less sleep than the control group may indicate there are factors of ABS such as intoxication, that cause patients to lose sleep. A study of 393 participants who visited a hospital demonstrated a high correlation in men between alcohol use and sleep disturbances as well as the perception of poor quality of sleep²³. People who generate their own alcohol would likely suffer the same ill effects.

The General Diet Information section provides data similar to previous research in that people with ABS consume more water and less alcohol. In addition, they are less likely to eat meals away from home and more likely to avoid sweets. Candida overgrowth in the gut is associated with inflammation and other gastrointestinal diseases such as Crohn’s disease, ulcerative colitis, and gastric ulcers, which can lead to painful symptoms and loss of appetite²⁴.

These findings could also be due to the dietary changes made by patients who have become aware of dietary triggers and are making informed decisions to change their eating habits. Additional information should be collected on these and other patients to determine what dietary habits they had historically, versus the dietary patterns adopted once they became aware of ABS symptoms, triggers, and treatments.

The most interesting segment of the survey comparison is the Health History section. The participants in the ABS group are much more allergic overall than the 11,297 respondents of the AGP. The ABS group is more likely to have seasonal allergies, have drug allergies, be allergic to pet dander, be allergic to bee stings, and be allergic to poison ivy or poison oak. Overall, people who suffer from ABS and those who live with them are a much more atopic group than those in the AGP. These data suggest a possible link to immune systems that may be interacting with gut dysbiosis in the expression of symptoms.

Food sensitivities are closely related to other types of allergic reactions. Fermentable carbohydrates termed ‘FODMAPs’ (fermentable oligo- di- mono-saccharides and polyols) occur in many foods and are associated with many gastrointestinal symptoms such as IBS. Such sensitivities and even intolerances have been linked to eczema, asthma, food allergies, and allergic rhinitis²⁵.

People with ABS have gut dysbiosis by the very presence of an over-colonized fermenting yeast or bacteria and by the production of endogenous alcohol. Symptoms of gut fermentation may mimic food sensitivities and it would make sense that fermentable carbohydrates would create additional gastrointestinal symptoms. The fact that the ABS group is more allergic follows the theory of ‘allergic march’ where there are patterns of co-morbidities of allergic disease and even progression rather than a single disease²⁶. This hypothesis should be explored further.

The significant difference that people in the ABS group are more likely to own a pet, indicates animals could be a possible contributing factor. Even though people with ABS are more likely to be allergic to pet dander, they are also more likely to own a pet. This raises the question of whether owning a pet further exacerbates fermentation and symptoms. And it also raises the question whether an allergy to pet dander contributes somehow to gut fermentation.

One limitation to the study is the online nature of the survey. Not all potential participants have access to a computer or are willing to take an online survey. These people may differ from those who do have a computer and are willing to take an online survey. Another limitation to the study is the small sample size. Significance from other questions may not have been detected with such a small ABS sample. The lack of significant results in the factors mentioned above leads us to believe these factors are not related to the development of ABS but they might still be important in future studies. While we certainly need to focus in on the significant differences, we should dig deeper into other factors to see how ABS develops. An important study would be to look at these and other factors in patients when they are first diagnosed prior to treatment.

Our ABS sample size is seemingly small but considering the rarity of ABS, we felt fortunate to have as many participants as we did. Because our analysis contained patients from four continents and our response rate was 88%, we are confident in generalizing our results to the growing field of ABS.

Conclusion

Auto-Brewery Syndrome is a rarely diagnosed syndrome affecting people worldwide. While many case studies have been published there is scant research on ABS. Very little is known about lifestyle factors such as health, diet, and past medical history of ABS patients that may contribute to symptoms. Using questions from the nationwide AGP survey, our research showed 12 statistically significant differences between the group of ABS patients and housemates, and the more general group from the AGP.

The findings in this case control study give insights into common factors experienced by people with ABS and their household members. We believe our findings raise interesting hypotheses about co-morbidities. These hypotheses warrant additional research into influences that may impact the microbiome and lead to ABS. We recommend that providers in emergency departments and gastroenterology practices retain an open mind when they meet intoxicated patients who insist they have not been drinking. The more we learn about ABS the more we can respond with compassion and science-based information.

Data availability