Continuing Education Activity

Auto-brewery syndrome or gut fermentation syndrome is a condition in which ethanol is produced through endogenous fermentation by fungi or bacteria in the gastrointestinal (GI) system, oral cavity, or urinary system. Patients with auto-brewery syndrome present with many of the signs and symptoms of alcohol intoxication while denying the intake of alcohol and often report a high-sugar, high-carbohydrate diet. Several strains of fermenting yeasts and rare bacteria are identified as pathogens. This activity reviews the etiology and pathophysiology of auto-brewery syndrome and highlights the role of the interprofessional team in its diagnosis and management.

Objectives:

• Identify the etiology of auto-brewery syndrome.

• Review the evaluation of auto-brewery syndrome.

• Describe the treatment and management options available for auto-brewery syndrome.

• Explain the interprofessional team strategies for improving care coordination and communication regarding the management of patients with auto-brewery syndrome.

Introduction

Auto-brewery syndrome or gut fermentation syndrome is a condition in which ethanol is produced through endogenous fermentation by fungi or bacteria in the gastrointestinal system, oral cavity, or urinary system. Patients with auto-brewery syndrome present with many of the signs and symptoms of alcohol intoxication while denying an intake of alcohol and often report a high-sugar, high-carbohydrate diet.[1] The production of endogenous ethanol occurs in minute quantities as part of normal digestion, but when fermenting yeast or bacteria becomes pathogenic, extreme blood alcohol levels may result. Auto-brewery syndrome is more prevalent in patients with co-morbidities such as diabetes, obesity, and Crohn disease [2][3] but can occur in otherwise healthy individuals.[4] Several strains of fermenting yeasts and rare bacteria are identified as pathogens. While auto-brewery syndrome is rarely diagnosed, it is probably underdiagnosed.[5] Even rarer are two cases of auto-brewery syndrome identified, one in the oral cavity [6] and one in the urinary bladder.[7]

Etiology

Various yeasts from the Candida and Saccharomyces families are commensals turned pathogenic that cause auto-brewery syndrome. Several strains of bacteria are also known to ferment ethanol.

• Fermenting yeasts such as Saccharomyces cerevisiae, S boulardii, and various strains of Candida, including C glabrata, C albicans, C kefyr, and C parapsilosis are identified as causes of this condition.[8]
• The bacteria Klebsiella pneumonia, Enterococcus faecium, E faecalis, and Citrobacter freundii are implicated in at least 1 case each.[5][9][10][11]
• Existing conditions, such as diabetes or liver problems, can impact the diagnosis of ABS. Patients with type 2 diabetes mellitus (DM) or liver cirrhosis (LC) tested higher for endogenous ethanol (EnEth) levels than a control group without the disease. However, the EnEth levels peaked highest in a group of patients with both type 2 DM and LC, where the blood alcohol concentration reached 22.3 mg/dL.[2][12]
• Four common yeasts (Candida albicans, Candida tropicalis, Saccharomyces cerevisiae, and Torulopsis glabrata) were combined with infant formulas. Ethanol production was measured after 24 and 48 hours. The quantities of ethanol produced suggest an explanation for patients exhibiting auto-brewery syndrome.[13]
• Bacterial production of EnEth is involved in the development of metabolic dysfunction-associated steatotic liver disease (MASLD).[14][15] Higher levels of EnEth are also detected in obese patients and those with metabolic dysfunction-associated steatohepatitis (MASH).[16][17][18][19]

Epidemiology

Auto-brewery syndrome is a rare condition. The disease has been identified in both male and female adults and children in many countries and is likely underdiagnosed.

Pathophysiology

A perturbation of the gut, oral, or urinary microbiome or mycobiome is the underlying condition that allows fermenting microbes to over-colonize. Such disturbances are caused by a diet high in carbohydrates and refined foods and the overuse of antibiotic and non-antibiotic drugs in food and medicine.[20][21] Other underlying conditions may contribute to the pathogenesis of auto-brewery syndrome:

• Auto-brewery syndrome occurred in several patients with short bowel syndrome, pseudoobstruction, or small intestinal bacterial overgrowth (SIBO) who exhibited signs and symptoms of alcohol intoxication.[9][22][23][24]
• Researchers compared patients with auto-brewery syndrome (ABS) (N= 28; 16 men and 12 women) to an asymptomatic group (N= 18) regarding lifestyle and health, diet, and medical history. The data show significant differences between the groups. The ABS group reported poorer overall health and more food sensitivities. They consume more water, less tea, coffee, dairy, and candy; they eat out less, cook more at home, and have more aversion to starch. The ABS members also report bad breath, diarrhea, and bowel changes. Most importantly, patients with auto-brewery syndrome report using antibiotics for a longer time. While not statistically significant, the people in the ABS group also report more diagnosed gastrointestinal disorders.[4]
• Researchers compared patients with ABS (N=2 8; 16 men and 12 women) to a cohort of the American Gut Project (AGP; N= 11,237) on a survey of 30 questions about lifestyle and health, diet, and medical history. The data show that patients with ABS and their household members are more likely than participants of the AGP to own a pet, get less sleep, and have a lesser quality of bowel movements. Also, the ABS participants drink more water and less alcohol, eat at home more often, and report eating fewer sweets. Most significantly, the ABS group has a higher presence of non-food allergies compared to the AGP group.[25]
• Measurements of endogenous ethanol have been made, and in one instance, a patient registered an ethanol concentration of greater than 400 mg/dL. In these individuals, endogenous ethanol appears after the consumption of a high carbohydrate diet. Stress and skipping meals may also exacerbate these high ethanol levels.[5]
• A genetic polymorphism that results in reduced activity of aldehyde dehydrogenases enzymes involved in the hepatic metabolism of ethanol and a first-pass metabolism might explain the ethnic differences in rates of endogenous ethanol production and clearance.[26] However, the enzymes have not been studied in auto-brewery syndrome patients specifically.

History and Physical

Auto-brewery syndrome has significant effects on a person’s life. The patient may experience side effects of vomiting, belching, chronic fatigue syndrome, dizziness, loss of coordination, disorientation, veisalgia, and irritable bowel symptoms. Chronic fatigue syndrome can result in health problems such as anxiety, depression, and poor productivity. Because of the production of significant alcohol levels, people can test over the legal driving limit without consuming any alcohol. The randomness of intoxication episodes can result in difficulties for the patient, including injuries from falls, legal difficulties following driving citations, and strain on social relationships.[12][27] The obscurity of the condition challenges practitioners to diagnose and find a successful treatment. A comprehensive history and physical is essential, including a detailed diet history. Family members should supplement the intake history since patients may not remember their episodes of intoxication or what they ate prior to an episode.

Evaluation

Patients may not initially present with signs and symptoms of intoxication but may report neurological symptoms, loss of coordination, and mood changes. Auto-brewery syndrome should be considered in any patient presenting with an elevated blood alcohol level who denies ingestion of alcohol, including those arrested for driving while impaired.[5] Auto-brewery syndrome is more likely in a patient with chronic intestinal obstruction, gastroparesis, diabetes, or liver dysfunction such as MASLD or MASH. An interprofessional approach that includes a psychiatric evaluation should be employed. 

Evaluation should include:

• A complete history and physical; include history from family members regarding diet and alcohol intake and episodes of unexplained intoxication
• Lab tests including complete blood count, metabolic panel, blood alcohol level, drug screen, and stool culture and sensitivity (bacterial and fungal)
• Elimination of other primary causes such as head injury, secret drinking, psych diagnosis
• A 24-hour observation with a high carbohydrate diet and a carbohydrate challenge of 200 g glucose with blood alcohol content and breath alcohol concentration testing at intervals of 0, 1/2, 1, 2, 4, 8, 16, and 24 hours; confirmation of auto-brewery syndrome if levels are elevated during the test.
• Upper and lower endoscopy with samples for culture and sensitivity (bacterial and fungal)[5]

Clinicians should be aware that not all patients have an episode (or flare) within 24 hours depending on transit time and location of fermenting microbes.

Treatment / Management

A coordinated treatment program should include patient input for compliance.

• Immediate care: The patient with an extremely high blood alcohol level should be treated for acute alcohol poisoning and stabilized.
• Drug therapy: Prescribe drug therapy based on culture and sensitivity results for the identified yeast or bacteria. Most patients require a course of one or more of the azoles or polyenes. Rare or resistant microbes require an echinocandin or an antibiotic.
• Diet therapy: An essential treatment of auto-brewery syndrome is diet modification requiring high protein and low carbohydrates until symptoms subside. Sugar is fermented into alcohol, and a diet that eliminates simple and complex sugars will decrease the alcohol fermented from the gastrointestinal and genitourinary tract.
• Supplements: Multistrain probiotic supplements help balance bacteria in the gastrointestinal tract and have been used in the treatment of auto-brewery syndrome but have yet to be studied as a treatment

The risk of relapse of auto-brewery syndrome is lessened by avoiding carbohydrates. A nutritionist should be involved in the treatment and management of the disease. Anything that causes an imbalance between harmful and beneficial bacteria can potentially increase fermentation in the gut. Antibiotics should be avoided if possible. If a course of antibiotics is required, a plan should be in place to again test for fermenting pathogens and treat them if necessary. In single and various combinations, dietary carbohydrate control, antifungal or antibiotic therapy, general antibiotic avoidance, and probiotics have all been reported as successful treatments. However, patients with long-term, chronic relapses may require fecal microbiota transplants.[28]

Differential Diagnosis

Rule out other possible causes such as head injury, psychiatric disorder, and hidden drinking. Auto-brewery syndrome should also be included in the differential diagnosis for D-lactic acidosis.[29] Auto-brewery syndrome should always be considered in the differential diagnosis of patients who are not consuming alcohol and yet exhibit the signs and symptoms of alcohol intoxication; particularly if they are also consuming a high carbohydrate diet or have a history of antibiotic use.

Prognosis

Some patients can resolve symptoms of auto-brewery syndrome by stopping antibiotics and following a sugar-free, low-carbohydrate diet.[22] Others may require antifungals or antibiotics, along with diet modification. Probiotics, a low carbohydrate diet, and avoidance of antibiotics may help prevent relapse. Some patients have chronic relapses and are unable to find a balance for their microbiome and continue to have episodes of drunkenness. 

Complications

Most patients can resume a normal diet and lifestyle after one treatment. Other patients may relapse one or more times, especially if treated with antibiotics that disturb the gut microbiome. However, Auto-brewery syndrome can have a profound effect on patients and families. In many cases, auto-brewery syndrome is mistaken for alcohol consumption, creating social and legal issues. ABS disrupts lives and relationships and puts stress on everyone involved. Even after symptoms have resolved, long-term exposure to endogenous ethanol can result in cravings for and addiction to alcohol with subsequent drinking. Alcohol use disorder may result during or after treatment.

Postoperative and Rehabilitation Care

Some combination of diet modification, drug therapy, and probiotics usually eliminates symptoms. Patients and healthcare providers should be aware of the possibility of relapse of symptoms. Occasionally GI cultures demonstrate an additional yeast that was resistant to the initial drug therapy. Cases with chronic relapses may be considered for fecal microbiota transplant. Some patients may also require an alcohol treatment program. 

Consultations

Consult gastroenterology, infectious disease, and a registered nutritionist.

Deterrence and Patient Education

Patients should avoid sugars and carbohydrates and eat a diet higher in proteins during treatment. In the long term, patients should be educated on how to maintain a low carbohydrate diet, avoid dietary antibiotics, and abstain from drinking alcohol. Patients should be taught about the microbiome and to avoid taking antibiotics unless necessary. If given antibiotics, they should ask their provider for a plan to prevent relapse. Patients should be educated about the possibility of alcohol use disorder during treatment as well as after symptoms are resolved and be given referrals for alcohol treatment if needed.

Enhancing Healthcare Team Outcomes

Any patient with an elevated blood alcohol level who denies alcohol ingestion should be treated with empathy and compassion by all team members. The diagnosis and management of auto-brewery syndrome (gut fermentation syndrome) are best done with an interprofessional team that includes a primary provider, a gastroenterologist, an infectious disease specialist, a nurse, and a nutritionist. An endocrinologist should be involved if the patient has diabetes and a hepatologist should be consulted in the event liver complications are detected. Pharmacists review medical treatments, check for drug-drug interactions, and provide patient education. Gastroenterology nurse specialists provide patient and family education, monitor patient progress, and report back to the team. After diagnosis and stabilization, most patients can be treated as an outpatient. The main goal is to promote patient compliance with dietary changes, supplements, and if needed, medication. As symptoms subside, the healthcare team should assess alcohol cravings and make appropriate referrals.