Auto-brewery syndrome

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Auto-brewery syndrome
Other namesGut fermentation syndrome, Endogenous ethanol fermentation
2401 Components of the Digestive System.jpg
Digestive system

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. [1] ABS is a rare medical condition in which intoxicating quantities of ethanol are produced through endogenous fermentation within the digestive system. [2] The organisms responsible for ABS include various yeasts and bacteria, including Saccharomyces cerevisiae , S. boulardii , Candida albicans , C. tropicalis , C. krusei , C. glabrata , C. parapsilosis , Kluyveromyces marxianus , Klebsiella pneumoniae , and Enterococcus faecium . [1] These organisms use lactic acid fermentation or mixed acid fermentation pathways to produce an ethanol end product. [3] 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. [4]

Contents

Researchers speculate the underlying causes of ABS are related to prolonged antibiotic use, [5] poor nutrition and/or diets high in carbohydrates, [6] and to pre-existing conditions such as diabetes and genetic variations that result in improper liver enzyme activity. [7] In the last case, decreased activity of aldehyde dehydrogenase can result in accumulation of ethanol in the gut, leading to fermentation. [7] Any of these conditions, alone or in combination, could cause ABS, and result in dysbiosis of the microbiome. [5]

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. [7]

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. [8] Mood changes and other neurological problems have also been reported. [1] Several cases in the United States and one in Belgium have argued endogenous fermentation as a defense against drunk driving. [7] [9]

Risk factors

Certain clinical conditions such as type 2 diabetes mellitus and liver cirrhosis have been identified as producing higher levels of endogenous ethanol. [4] Research has also shown that Klebsiella bacteria can similarly ferment carbohydrates to alcohol in the gut, which can accelerate non-alcoholic fatty liver disease. [10] Gut fermentation can occur in patients with short bowel syndrome after surgical resection because of fermentation of malabsorbed carbohydrates. [1]

Kaji et al. noticed a correlation between this syndrome and previous abdominal surgeries and disturbances, such as a dilation of the duodenum. Stagnation of the contents ensues, which favors proliferation of the causative organisms. [8]

Gut fermentation syndrome has been investigated, but eliminated, as a possible cause of sudden infant death syndrome. [11]

Metabolic action

Ethanol fermentation cycle Ethanol fermentation.jpg
Ethanol fermentation cycle

Fermentation is a biochemical process during which yeast and certain bacteria convert sugars to ethanol, carbon dioxide, as well as other metabolic byproducts. [12] [13] The fermentation pathway involves pyruvate formed from yeast in the EMP pathway, while some bacteria obtain pyruvate through the ED pathway. [12] Pyruvate is then decarboxylated to acetaldehyde in a reaction involving the enzyme pyruvate decarboxylase. [12] Reduction of acetaldehyde to ethanol produces NAD+, which is catalyzed by alcohol dehydrogenase (ADH). [12] ADH rids the body of alcohol through a process called first pass metabolism. [7] However, if the rate of ethanol breakdown is less than the rate of production, intoxication ensues.[ citation needed ]

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. In gas chromatography the breath or blood is heated so that the different components of the vapor or blood separate. The volatile compounds then pass through a chromatograph that isolates ethanol from the other volatiles so that it can be quantified. [14]

More convenient methods include serum measurements and breathalyzers, especially during an acute attack at home. [10] Different countries have different baselines for blood alcohol levels when identifying intoxication through breathalyzers. In the United States it is 0.08 g/dL.[ citation needed ]

In diagnosing ABS through serum measurement methods, patients must fast in order that baseline blood alcohol and blood glucose levels can be established. They are then administered a dose of IG glucose to see if there is an increase in blood alcohol as well as blood sugar. [15] Blood glucose level can be measured with enzyme-amperometric biosensors, as well as with urine test strips. [16]  Many of these tests are performed in combination to rule out lab mistakes and alcohol ingestion so that the syndrome is not misdiagnosed. [10]

Treatment

First, patients diagnosed with ABS are treated for the immediate symptoms of alcohol intoxication. [1] Next, patients can take medications if they test positive for the types of fungi or bacteria that cause gut fermentation. For example, antifungals such as fluconazole or micafungin can be prescribed by a physician. [8] [6] [17] 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. [17] Patients also typically undergo a diet therapy where they are placed on a high protein, low carbohydrate diet to avoid the symptoms of ABS. [1] The treatments listed above can be used individually or in combination to reduce the effects of the syndrome. [1]

Case studies

Related Research Articles

<span class="mw-page-title-main">Alcohol intoxication</span> Behavioural and physical changes due to the consumption of alcohol

Alcohol intoxication, commonly described in higher doses as drunkenness or inebriation, and known in overdose as alcohol poisoning, is the behavior and physical effects caused by recent consumption of alcohol. The technical term intoxication in common speech may suggest that a large amount of alcohol has been consumed, leading to accompanying physical symptoms and deleterious health effects. Mild intoxication is mostly referred to by slang terms such as tipsy or buzzed. In addition to the toxicity of ethanol, the main psychoactive component of alcoholic beverages, other physiological symptoms may arise from the activity of acetaldehyde, a metabolite of alcohol. These effects may not arise until hours after ingestion and may contribute to a condition colloquially known as a hangover.

Flatulence is the expulsion of gas from the intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swallowed environmental air, and hence flatus is not entirely generated in the stomach or bowels. The scientific study of this area of medicine is termed flatology.

<span class="mw-page-title-main">Urinary tract infection</span> Infection that affects part of the urinary tract

A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyelonephritis). Symptoms from a lower urinary tract infection include suprapubic pain, painful urination (dysuria), frequency and urgency of urination despite having an empty bladder. Symptoms of a kidney infection, on the other hand, are more systemic and include fever or flank pain usually in addition to the symptoms of a lower UTI. Rarely, the urine may appear bloody. Symptoms may be vague or non-specific at the extremities of age.

<span class="mw-page-title-main">Lactic acid</span> Organic acid

Lactic acid is an organic acid. It has the molecular formula C3H6O3. It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natural sources. Lactic acid is an alpha-hydroxy acid (AHA) due to the presence of a hydroxyl group adjacent to the carboxyl group. It is used as a synthetic intermediate in many organic synthesis industries and in various biochemical industries. The conjugate base of lactic acid is called lactate (or the lactate anion). The name of the derived acyl group is lactoyl.

<span class="mw-page-title-main">Lactic acidosis</span> Metabolic medical condition

Lactic acidosis refers to the process leading to the production of lactate by anaerobic metabolism. It increases hydrogen ion concentration tending to the state of acidemia or low pH. The result can be detected with high levels of lactate and low levels of bicarbonate. This is usually considered the result of illness but also results from strenuous exercise. The effect on pH is moderated by the presence of respiratory compensation.

<span class="mw-page-title-main">Wernicke–Korsakoff syndrome</span> Combined presence of Wernickes encephalopathy (WE) and Korsakoffs syndrome

Wernicke-Korsakoff syndrome (WKS) is the combined presence of Wernicke encephalopathy (WE) and alcoholic Korsakoff syndrome. Due to the close relationship between these two disorders, people with either are usually diagnosed with WKS as a single syndrome. It mainly causes vision changes, ataxia and impaired memory.

<span class="mw-page-title-main">Hyperuricemia</span> Excess uric acid in the blood

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for males, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

<span class="mw-page-title-main">Hematuria</span> Presence of blood in urine

Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. "Gross hematuria" occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable with a microscope or laboratory test. Blood that enters and mixes with the urine can come from any location within the urinary system, including the kidney, ureter, urinary bladder, urethra, and in men, the prostate. Common causes of hematuria include urinary tract infection (UTI), kidney stones, viral illness, trauma, bladder cancer, and exercise. These causes are grouped into glomerular and non-glomerular causes, depending on the involvement of the glomerulus of the kidney. But not all red urine is hematuria. Other substances such as certain medications and foods can cause urine to appear red. Menstruation in women may also cause the appearance of hematuria and may result in a positive urine dipstick test for hematuria. A urine dipstick test may also give an incorrect positive result for hematuria if there are other substances in the urine such as myoglobin, a protein excreted into urine during rhabdomyolysis. A positive urine dipstick test should be confirmed with microscopy, where hematuria is defined by three or more red blood cells per high power field. When hematuria is detected, a thorough history and physical examination with appropriate further evaluation can help determine the underlying cause.

<span class="mw-page-title-main">Ethanol fermentation</span> Biological process that produces ethanol and carbon dioxide as by-products

Ethanol fermentation, also called alcoholic fermentation, is a biological process which converts sugars such as glucose, fructose, and sucrose into cellular energy, producing ethanol and carbon dioxide as by-products. Because yeasts perform this conversion in the absence of oxygen, alcoholic fermentation is considered an anaerobic process. It also takes place in some species of fish where it provides energy when oxygen is scarce.

<span class="mw-page-title-main">Small intestinal bacterial overgrowth</span> Medical condition

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<span class="mw-page-title-main">Trimethylaminuria</span> Medical condition

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<span class="mw-page-title-main">Glycosuria</span> Medical condition

Glycosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reabsorb all of the filtered glucose from the tubular fluid back into the bloodstream. Glycosuria is nearly always caused by an elevated blood sugar level, most commonly due to untreated diabetes. Rarely, glycosuria is due to an intrinsic problem with glucose reabsorption within the kidneys, producing a condition termed renal glycosuria. Glycosuria leads to excessive water loss into the urine with resultant dehydration, a process called osmotic diuresis.

<span class="mw-page-title-main">Glucuronic acid</span> Sugar acid

Glucuronic acid is a uronic acid that was first isolated from urine. It is found in many gums such as gum arabic, xanthan, and kombucha tea and is important for the metabolism of microorganisms, plants and animals.

<span class="mw-page-title-main">Fermentation</span> Metabolic redox process producing energy in the absence of oxygen.

Fermentation is a type of redox metabolism carried out in the absence of oxygen. During fermentation, organic molecules are catabolized and donate electrons to other organic molecules. In the process, ATP and organic end products are formed.

<span class="mw-page-title-main">Acute prostatitis</span> Serious bacterial infection of the prostate gland

Acute prostatitis is a serious bacterial infection of the prostate gland. This infection is a medical emergency. It should be distinguished from other forms of prostatitis such as chronic bacterial prostatitis and chronic pelvic pain syndrome (CPPS).

Urologic diseases or conditions include urinary tract infections, kidney stones, bladder control problems, and prostate problems, among others. Some urologic conditions do not affect a person for that long and some are lifetime conditions. Kidney diseases are normally investigated and treated by nephrologists, while the specialty of urology deals with problems in the other organs. Gynecologists may deal with problems of incontinence in women.

<span class="mw-page-title-main">Purple urine bag syndrome</span> Medical condition

Purple urine bag syndrome (PUBS) is a medical syndrome where purple discoloration of urine collection bag occurs in people with urinary catheters and co-existent urinary tract infections. PUBS is most prevalent in elderly females with constipation. Constipation alters the gut bacteria, reducing gastrointestinal motility and leading to increased growth of bacteria in the colon. High bacterial counts in urine are the most important factor causing purple urine bag syndrome. Bacteria in urine produce the enzyme indoxyl sulfatase. This converts indoxyl sulfate in the urine into the red and blue colored compounds indirubin and indigo. People with urinary tract infections using catheters will increase the conversion of indoxyl sulfatase to indirubin and indigo. Indirubin dissolves in plastic and therefore causes urine discoloration. The purple discoloration is the result of reaction between indirubin and plastic urine bags, as well as the presence of indigo. Bacteria in the urine can be found through bacteria culture test. People with purple urine bag syndrome may present with elevated bacterial loads on their culture tests when compared to those who are not affected by this syndrome. The most commonly implicated bacteria are Providencia stuartii, Providencia rettgeri, Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli, Morganella morganii, and Pseudomonas aeruginosa. Purple urine bag syndrome treatment should aim for underlying issues rather than the condition itself. The purple discoloration is harmless and can be resolved with treatments targeted to specific bacteria or any underlying medical conditions. Treatment also consists of providing comfort to both patients and their family, administering antibiotics and performing regular catheter changes. The prognosis is good, however, the morbidity and mortality rates associated with PUBS are elevated depending on patient's underlying health status.

<span class="mw-page-title-main">Emphysematous cystitis</span> Medical condition

Emphysematous cystitis is a rare type of infection of the bladder wall by gas-forming bacteria or fungi. The most frequent offending organism is E. coli. Other gram negative bacteria, including Klebsiella and Proteus are also commonly isolated. Fungi, such as Candida, have also been reported as causative organisms. Citrobacter and Enterococci have also been found to cause emphysematous cystitis. Although it is a rare type of bladder infection, it is the most common type of all gas-forming bladder infections. The condition is characterized by the formation of air bubbles in and around the bladder wall. The gas found in the bladder consists of nitrogen, hydrogen, oxygen, and carbon dioxide. The disease most commonly affects elderly diabetic and immunocompromised patients. The first case was identified in a post-mortem examination in 1888.

<span class="mw-page-title-main">Metadoxine</span> Medication used for alcohol intoxication

Metadoxine, also known as pyridoxine-pyrrolidone carboxylate, is a drug used to treat chronic and acute alcohol intoxication. Metadoxine accelerates alcohol clearance from the blood.

<span class="mw-page-title-main">Alcohol (drug)</span> Active ingredient in fermented drinks

Alcohol, sometimes referred to by the chemical name ethanol, is the second most consumed psychoactive drug globally behind caffeine, and alcohol use disorders are the most prevalent of all substance use disorders worldwide. Alcohol is a central nervous system (CNS) depressant, decreasing electrical activity of neurons in the brain. The World Health Organization (WHO) classifies alcohol as a toxic, psychoactive, dependence-producing, and carcinogenic substance.

References

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  2. ↑ Kaji H, Asanuma Y, Yahara O, Shibue H, Hisamura M, Saito N, et al. (1984). "Intragastrointestinal alcohol fermentation syndrome: report of two cases and review of the literature". Journal of the Forensic Science Society. 24 (5): 461–71. doi:10.1016/S0015-7368(84)72325-5. PMID   6520589.
  3. ↑ Fayemiwo SA, Adegboro B (2013-11-20). "Gut fermentation syndrome". African Journal of Clinical and Experimental Microbiology. 15 (1): 48–50. doi: 10.4314/ajcem.v15i1.8 . ISSN   1595-689X.
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  6. 1 2 Saverimuttu J, Malik F, Arulthasan M, Wickremesinghe P (October 2019). "A Case of Auto-brewery Syndrome Treated with Micafungin". Cureus. 11 (10): e5904. doi: 10.7759/cureus.5904 . PMC   6853272 . PMID   31777691.
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  9. ↑ "2 promille alcohol in zijn bloed, maar toch vrijgesproken voor rijden onder invloed: man uit Brugge lijdt aan autobrouwerijsyndroom". VRT (in Dutch). 22 April 2024. Retrieved 23 April 2024.
  10. 1 2 3 Yuan J, Chen C, Cui J, Lu J, Yan C, Wei X, et al. (October 2019). "Fatty Liver Disease Caused by High-Alcohol-Producing Klebsiella pneumoniae". Cell Metabolism. 30 (4): 675–688.e7. doi: 10.1016/j.cmet.2019.08.018 . PMID   31543403.
  11. ↑ Geertinger P, Bodenhoff J, Helweg-Larsen K, Lund A (September 1982). "Endogenous alcohol production by intestinal fermentation in sudden infant death". Zeitschrift für Rechtsmedizin. Journal of Legal Medicine. 89 (3): 167–72. doi:10.1007/BF01873798. PMID   6760604. S2CID   29917601.
  12. 1 2 3 4 Fath BD, Jørgensen SE (23 August 2018). Encyclopedia of ecology. Fath, Brian D. (Second ed.). Amsterdam, Netherlands. ISBN   978-0-444-64130-4. OCLC   1054599976.{{cite book}}: CS1 maint: location missing publisher (link)
  13. ↑ Mendez ML (2016). Electronic noses and tongues in food science. London: Academic Press. ISBN   978-0-12-800402-9. OCLC   940961460.
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  15. ↑ Eaton KK (November 1991). "Gut fermentation: a reappraisal of an old clinical condition with diagnostic tests and management: discussion paper". Journal of the Royal Society of Medicine. 84 (11): 669–71. doi:10.1080/13590840410001734929. PMC   1295472 . PMID   1744875.
  16. ↑ Simic M, Ajdukovic N, Veselinovic I, Mitrovic M, Djurendic-Brenesel M (March 2012). "Endogenous ethanol production in patients with diabetes mellitus as a medicolegal problem". Forensic Science International. 216 (1–3): 97–100. doi:10.1016/j.forsciint.2011.09.003. PMID   21945304.
  17. 1 2 Malik F, Wickremesinghe P, Saverimuttu J (August 2019). "Case report and literature review of auto-brewery syndrome: probably an underdiagnosed medical condition". BMJ Open Gastroenterology. 6 (1): e000325. doi:10.1136/bmjgast-2019-000325. PMC   6688673 . PMID   31423320.
  18. ↑ Spinucci G, Guidetti M, Lanzoni E, Pironi L (July 2006). "Endogenous ethanol production in a patient with chronic intestinal pseudo-obstruction and small intestinal bacterial overgrowth". European Journal of Gastroenterology & Hepatology. 18 (7): 799–802. doi:10.1097/01.meg.0000223906.55245.61. PMID   16772842.
  19. ↑ Dashan A, Donovan K (August 2001). "Auto-brewery syndrome in a child with short gut syndrome: case report and review of the literature". J Pediatr Gastroenterol Nutr. 33 (2): 214–215. doi:10.1097/00005176-200108000-00024. PMID   11568528.
  20. ↑ "Auto-Brewery Syndrome: Woman Failed Urine Tests As Her Bladder Was Brewing Alcohol". International Business Times . 26 February 2020.
  21. ↑ Kruckenberg KM, DiMartini AF, Rymer JA, Pasculle AW, Tamama K (February 2020). "Urinary Auto-brewery Syndrome: A Case Report". Annals of Internal Medicine. 172 (10): 702–704. doi:10.7326/L19-0661. PMID   32092761. S2CID   211475605.
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