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| Auto-brewery syndrome | |
| Other names | Gut fermentation syndrome |
 | |
| Digestive system | |
Auto Brewery Syndrome (ABS), also referred to 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] The organisms responsible for ABS include various yeasts and bacteria like Saccharomyces cerevisiae, S. boulardii, Candida albicans, C. tropicalis, C. krusei, C. glabrata, C. kefyr, Torulopsis glabrata and Klebsiella pneumoniae.[2] These classes of bacteria and fungi use lactic acid fermentation or mixed acid fermentation pathways to produce an ethanol end product.[3] The ethanol generated from these pathways is readily absorbed in the small intestine, causing an increase in blood alcohol concentrations that produce the effects of intoxication without the consumption of alcohol.[4]
Researchers speculate the underlying causes of ABS are related to prolonged antibiotic use[5], poor nutrition and/or diets high in carbohydrates[6], inflammatory bowel disease, diabetes, low immune system activity, 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. This condition can lead to more serious complications related to alcoholism, such as nonalcoholic fatty liver disease (NAFLD).[7]
Symptoms
Symptoms that usually accompany Auto Brewery Syndrome 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] This disease can have profound effects on daily life, leading to familial, employment, and other social problems and complications. Several cases in the United States have argued endogenous fermentation as a defense against drunk driving.[9]
Mechanism of Action
Fermentation is a biochemical process during which yeast, bacteria and some fungi convert sugars to ethanol, carbon dioxide, as well as other metabolic byproducts1,4. The fermentation pathway involves pyruvate which is formed by yeast in the EMP pathway while some bacteria obtain pyruvate through the ED pathway1. Pyruvate is then decarboxylated to acetaldehyde in a reaction involving the enzyme pyruvate decarboxylase1. Reduction of acetaldehyde to ethanol produces NAD+, which is catalyzed by alcohol dehydrogenase1. This biochemical process can take place in the human gut, with bacteria or fungi creating ethanol in the gastrointestinal system. An overgrowth of fermenting microbes can occur from large diets consisting of carbohydrates, processed, and refined foods.[7] The enzyme alcohol dehydrogenase is used to get rid of the alcohol that the body makes in the liver through a process called first pass metabolism [8]. Since alcohol, in small amounts, is in the food we digest the enzyme is spread all over the body. If the body produces more alcohol or the rate of breakdown is less than the rate of alcohol production than that is what will cause the feeling of intoxication.[9] Which increases the acetaldehyde and acetate concentrations which are two major metabolites of ethanol. While acetate is a substrate for fatty acid synthesis, acetaldehyde may lead to the production of ROS thereby contributing to NAFLD5.
Diagnosis
Alcohol levels within the body are usually detected through blood or breath. Currently, the best way to identify endogenous ethanol in the bloodstream is through gas chromatography. Gas chromatography 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.[10]
More convenient methods include serum measurements and breathalyzers, especially during an acute attack at home.[7] Different countries have different baselines for blood alcohol levels when identifying intoxication through breathalyzers. In the U.S., it is 0.08g/dL.
In diagnosing ABS through serum measurement methods, patients are made to fast for baseline blood alcohol and blood glucose levels, and then given a dose of IG glucose to see if there is an increase in blood alcohol as well as blood sugar.[11] An elevated blood glucose level can be measured with enzyme-amperometric biosensors. Urine test strips can also be used to confirm the presence of glucose.[12]
Many of these tests are performed in combination to rule out lab mistakes and alcohol ingestion so that the syndrome is not misdiagnosed.[7]
Potential Predispositions
There are certain clinical conditions such as type 2 diabetes mellitus and liver cirrhosis that have been identified to produce higher levels of endogenous ethanol.[4] Recent research has also shown that Klebsiella bacteria can similarly ferment carbohydrates to alcohol in the gut, which can accelerate non-alcoholic fatty liver disease.[7] 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. This could cause the contents to become stagnant and, in turn, favor proliferation of the causative organisms.[8]
Gut fermentation syndrome was previously investigated, but eliminated, as a possible cause of sudden infant death syndrome.[13]
Treatment
First, patients diagnosed with Auto Brewery Syndrome 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 antibiotics (such as?) can be prescribed by a physician.[8][14] Often, probiotics are given concurrently to ensure that the proper bacteria recolonize the gut, and to prevent recolonization by the microorganism(s) that caused the syndrome.[14] Patients also typically undergo a diet therapy where they are placed on a high protein, low carbohydrate diet to avoid the symptoms of Auto Brewery Syndrome.[1] All 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 fluconazole daily for 3 weeks, and his symptoms were resolved.[8]
- 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 the antifungal fluconazole and her symptoms resolved.[15]
- 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.[16]
References
- ^ a b c d e Painter, Kelly; Cordell, Barbara J.; Sticco, Kristin L. (2020), "Auto-brewery Syndrome (Gut Fermentation)", StatPearls, StatPearls Publishing, PMID 30020718, retrieved 2020-04-23
- ^ Huseyin, Chloe E.; O’Toole, Paul W.; Cotter, Paul D.; Scanlan, Pauline D. (2017-04-18). "Forgotten fungi—the gut mycobiome in human health and disease". FEMS Microbiology Reviews. 41 (4): 479–511. doi:10.1093/femsre/fuw047. ISSN 1574-6976.
- ^ 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.
- ^ a b Hafez, Em; Hamad, Ma; Fouad, M; Abdel-Lateff, A (2017-05). "Auto-brewery syndrome: Ethanol pseudo-toxicity in diabetic and hepatic patients". Human & Experimental Toxicology. 36 (5): 445–450. doi:10.1177/0960327116661400. ISSN 0960-3271.
{{cite journal}}: Check date values in:|date=(help) - ^ Cordell, Barbara Jean; Kanodia, Anup; Miller, Gregory K (2019-01). "Case–Control Research Study of Auto-Brewery Syndrome". Global Advances in Health and Medicine. 8: 216495611983756. doi:10.1177/2164956119837566. ISSN 2164-9561. PMC 6475837. PMID 31037230.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Saverimuttu, Jessie; Malik, Fahad; Arulthasan, Marutha; Wickremesinghe, Prasanna (2019-10-14). "A Case of Auto-brewery Syndrome Treated with Micafungin". Cureus. doi:10.7759/cureus.5904. ISSN 2168-8184. PMC 6853272. PMID 31777691.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b c d Yuan, Jing; Chen, Chen; Cui, Jinghua; Lu, Jing; Yan, Chao; Wei, Xiao; Zhao, Xiangna; Li, NanNan; Li, Shaoli; Xue, Guanhua; Cheng, Weiwei (2019-10-01). "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. ISSN 1932-7420. PMID 31543403.
- ^ a b c d Akhavan, Bobak J.; Ostrosky-Zeichner, Luis; Thomas, Eric J. (2019-09). "Drunk Without Drinking: A Case of Auto-Brewery Syndrome". ACG Case Reports Journal. 6 (9): e00208. doi:10.14309/crj.0000000000000208. ISSN 2326-3253. PMC 6831150. PMID 31750376.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Logan, B. K.; Jones, A. W. (2000-07). "Endogenous ethanol 'auto-brewery syndrome' as a drunk-driving defence challenge". Medicine, Science, and the Law. 40 (3): 206–215. doi:10.1177/002580240004000304. ISSN 0025-8024. PMID 10976182.
{{cite journal}}: Check date values in:|date=(help) - ^ Jones, A.W.; Mårdh, G.; Änggård, E. (1983). "Determination of endogenous ethanol in blood and breath by gas chromatography-mass spectrometry". Pharmacology Biochemistry and Behavior. 18: 267–272. doi:10.1016/0091-3057(83)90184-3. ISSN 0091-3057.
- ^ Eaton, K. K. (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.
- ^ Simic, M.; Ajdukovic, N.; Veselinovic, I.; Mitrovic, M.; Djurendic-Brenesel, M. (2012-03). "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. ISSN 0379-0738.
{{cite journal}}: Check date values in:|date=(help) - ^ Geertinger, P.; Bodenhoff, J.; Helweg-Larsen, K.; Lund, A. (1982-09). "Endogenous alcohol production by intestinal fermentation in sudden infant death". Zeitschrift für Rechtsmedizin. 89 (3): 167–172. doi:10.1007/BF01873798. ISSN 0044-3433.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Malik, Fahad; Wickremesinghe, Prasanna; Saverimuttu, Jessie (2019-08). "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. ISSN 2054-4774. PMC 6688673. PMID 31423320.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Cordell, Barbara; McCarthy, Justin (2013). "A Case Study of Gut Fermentation Syndrome (Auto-Brewery) with <i>Saccharomyces cerevisiae</i> as the Causative Organism". International Journal of Clinical Medicine. 04 (07): 309–312. doi:10.4236/ijcm.2013.47054. ISSN 2158-284X.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Spinucci, Giulio; Guidetti, Mariacristina; Lanzoni, Elisabetta; Pironi, Loris (2006-07). "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. ISSN 0954-691X.
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