Auto-brewery syndrome
   HOME

TheInfoList



OR:

Auto-brewery syndrome (ABS) (also known as gut fermentation syndrome, endogenous ethanol fermentation or drunkenness disease) is a condition characterized by the fermentation of ingested carbohydrates in the gastrointestinal tract of the body caused by bacteria or fungi. ABS is a rare medical condition in which intoxicating quantities of ethanol are produced through
endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...
fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...
within the
digestive system The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion (the tongue, salivary glands, pancreas, liver, and gallbladder). Digestion involves the breakdown of food into smaller and smaller compone ...
. The organisms responsible for ABS include various yeasts and bacteria, including '' Saccharomyces cerevisiae'', '' S. boulardii'', '' Candida albicans'', '' C. tropicalis'', '' C. krusei'', '' C. glabrata'', '' C. kefyr'', '' C. parapsilosis'', '' Klebsiella pneumoniae'', and ''
Enterococcus faecium ''Enterococcus faecium'' is a Gram-positive, gamma-hemolytic or non- hemolytic bacterium in the genus ''Enterococcus''. It can be commensal (innocuous, coexisting organism) in the gastrointestinal tract of humans and animals, but it may also be ...
''. These organisms use
lactic acid fermentation Lactic acid fermentation is a metabolic process by which glucose or other six-carbon sugars (also, disaccharides of six-carbon sugars, e.g. sucrose or lactose) are converted into cellular energy and the metabolite lactate, which is lactic acid ...
or mixed acid fermentation pathways to produce an ethanol end product. The ethanol generated from these pathways is absorbed in the small intestine, causing an increase in blood alcohol concentrations that produce the effects of intoxication without the consumption of alcohol. Researchers speculate the underlying causes of ABS are related to prolonged antibiotic use, poor nutrition and/or diets high in carbohydrates, and to pre-existing conditions such as diabetes and genetic variations that result in improper liver enzyme activity. In the latter case, decreased activity of aldehyde dehydrogenase can result in accumulation of ethanol in the gut, leading to fermentation. Any of these conditions, alone or in combination, could cause ABS, and result in dysbiosis of the microbiome. Another variant, urinary auto-brewery syndrome, is when the fermentation occurs in the urinary bladder rather than the gut. Claims of endogenous fermentation have been attempted as a defense against drunk driving charges, some of which have been successful, but the condition is so rare and under-researched they are currently not substantiated by available studies.


Symptoms and signs

This disease can have profound effects on everyday life. Symptoms that usually accompany ABS include elevated blood alcohol levels as well as symptoms consistent with alcohol intoxication—such as slurred speech, stumbling, loss of motor functions, dizziness, and belching. Mood changes and other neurological problems have also been reported. Several cases in the United States have argued endogenous fermentation as a defense against drunk driving.


Risk factors

There are certain clinical conditions such as
type 2 diabetes mellitus Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
and liver cirrhosis that have been identified to produce higher levels of endogenous ethanol. Research has also shown that '' Klebsiella'' bacteria can similarly ferment carbohydrates to alcohol in the gut, which can accelerate
non-alcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...
. Gut fermentation can occur in patients with short bowel syndrome after surgical resection because of fermentation of malabsorbed carbohydrates. Kaji et al. noticed a correlation between this syndrome and previous abdominal surgeries and disturbances, such as a dilation of the
duodenum The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...
. Stagnation of the contents ensues, which favors proliferation of the causative organisms. Gut fermentation syndrome was previously investigated, but eliminated, as a possible cause of sudden infant death syndrome.


Metabolic action

Fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...
is a biochemical process during which yeast and certain bacteria convert sugars to ethanol, carbon dioxide, as well as other metabolic byproducts. The fermentation pathway involves pyruvate formed from yeast in the EMP pathway, while some bacteria obtain pyruvate through the ED pathway.
Pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic aci ...
is then decarboxylated to
acetaldehyde Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
in a reaction involving the enzyme
pyruvate decarboxylase Pyruvate decarboxylase is an enzyme () that catalyses the decarboxylation of pyruvic acid to acetaldehyde. It is also called 2-oxo-acid carboxylase, alpha-ketoacid carboxylase, and pyruvic decarboxylase. In anaerobic conditions, this enzyme is ...
. Reduction of acetaldehyde to ethanol produces NAD+, which is catalyzed by alcohol dehydrogenase (ADH). ADH rids the body of alcohol through a process called first pass metabolism. However, if the rate of ethanol breakdown is less than the rate of production, intoxication ensues.


Diagnosis

Alcohol levels within the body are usually detected through blood or breath. The best way to identify endogenous ethanol in the bloodstream is through gas chromatography.
Gas chromatography Gas chromatography (GC) is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition. Typical uses of GC include testing the purity of a particular substance, ...
is where the breath or blood is heated so that the different components of the vapor or blood separate. The volatiles then pass through a chromatograph that isolates ethanol from the smaller volatiles so that it can be quantified. More convenient methods include serum measurements and breathalyzers, especially during an acute attack at home. Different countries have different baselines for blood alcohol levels when identifying intoxication through breathalyzers. In the United States, it is 0.08 g/dL. In diagnosing ABS through serum measurement methods, patients are made to fast in order to establish baseline blood alcohol and blood glucose levels. They are then administered a dose of IG glucose to see if there is an increase in blood alcohol as well as blood sugar. Blood glucose level can be measured with enzyme-amperometric biosensors, as well as with urine test strips. Many of these tests are performed in combination to rule out lab mistakes and alcohol ingestion so that the syndrome is not misdiagnosed.


Treatment

First, patients diagnosed with ABS are treated for the immediate symptoms of
alcohol intoxication Alcohol intoxication, also known as alcohol poisoning, commonly described as drunkenness or inebriation, is the negative behavior and physical effects caused by a recent consumption of alcohol. In addition to the toxicity of ethanol, the main p ...
. Next, patients can take medications if they test positive for the types of fungi or bacteria that cause gut
fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...
. For example,
antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as crypto ...
s such as fluconazole or
micafungin Micafungin, sold under the brand name Mycamine, is an echinochandin antifungal medication used to treat and prevent invasive fungal infections including candidemia, abscesses, and esophageal candidiasis. It inhibits the production of beta-1,3-g ...
can be prescribed by a physician. Often, probiotics are given concurrently to ensure that the proper bacteria recolonize the gut, and to prevent recolonization by the microorganisms that caused the syndrome. Patients also typically undergo a diet therapy where they are placed on a high protein, low carbohydrate diet to avoid the symptoms of ABS. The treatments listed above can be used individually or in combination to reduce the effects of the syndrome.


Case studies

* In 2019, a 25-year-old man presented with symptoms consistent with alcohol intoxication, including dizziness, slurred speech and nausea. He had no prior alcoholic drinks but had a blood alcohol level of 0.3 g/dL. The patient was given 100 mg of the antifungal fluconazole daily for 3 weeks, and his symptoms were resolved. * In 2004, a 44-year-old male was treated with the antibiotics clavulanic acid and amoxicillin for an unrelated condition. Eight days after being discharged, he returned to the emergency room with abdominal pain and belching and was in a state of confusion. An esophagogastroscopy showed the presence of ''S. cerevisiae'' and ''C. albicans'' in his gastric fluid, causing endogenous ethanol production. * In 2003, a 13-year-old girl with short gut syndrome suddenly developed symptoms of intoxication after eating a high-carbohydrate meal. She had no access to alcohol any time the symptoms were present. Her small intestine was colonized by two organisms: ''C. glabrata'' and ''S. cerevisiae''. She was treated with fluconazole and her symptoms resolved. * A case of urinary fermentation of carbohydrates by endogenous microorganisms leading to urinary ethanol has been reported. This single reported case is associated with diabetes due to the presence of sugar in the urine for the yeast to ferment. The person did not develop symptoms of intoxication, but did test positive in the urine for alcohol. Fermentation may continue after the urine is expressed, resulting in it developing an odor resembling wine.


References

{{Authority control Effects of psychoactive drugs Internal medicine Rare syndromes Rare infectious diseases