Carol Rees Parrish S RDN Series Itor Auto-Brewery Syndrome: A Schematic .
NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #212Carol Rees Parrish, MS, RDN, Series EditorAuto-Brewery Syndrome: A Schematicfor Diagnosis and Appropriate TreatmentFahad MalikPrasanna WickremesingheAtif SaleemAuto-Brewery Syndrome (ABS), also called Gut Fermentation Syndrome, is a rare, underdiagnosedmedical condition. This is caused by fermentation of ingested carbohydrate by gut fungi resultingin endogenous production of ethanol. Though this syndrome has been described in the medicalliterature for over 50 years, it still remains misunderstood with limited information regardingdiagnosis and treatment. The presenting symptoms and signs of ABS can be protean and mimicother clinical entities. This can make diagnosing this condition challenging. We propose thefollowing schematic for diagnosing and treating this unusual entity based on our ongoing studyof ABS patients. The initial step in confirming this diagnosis is a standardized carbohydratechallenge test which we have devised and studied in our ongoing cohort of ABS patients.INTRODUCTIONuto-Brewery Syndrome (ABS), which hasalso been described as Gut FermentationSyndrome, is a rare, underdiagnosed medicalcondition. In this condition, fermentation of ingestedcarbohydrate results in endogenous production ofethanol. This syndrome was originally described in1946 in a 5-year-old South African child undergoingAFahad Malik, MD Gastroenterology Fellow,United Health Services Wilson Medical Center,Department of Gastroenterology, Johnson City,NY Prasanna Wickremesinghe, MD, FACP, FACG,Gastroenterologist, Richmond University MedicalCenter, Department of Gastroenterology, Staten Island,NY Atif Saleem, MD Associate Program Director,United Health Services Wilson Medical Center,Department of Gastroenterology, Johnson City, NY10emergency laparotomy, during which a 3-inchposterior stomach wall tear was detected and alcoholnoted in the stomach.1 Multiple cases of ABS weresubsequently described in Japan during the 1970s.In these cases, identified yeast forms were mostlyCandida species as the causative agent.2 ABS ismore common in patients with chronic medicalconditions such as diabetes, inflammatory boweldisease (Crohn’s disease patients with strictures),short bowel syndrome or immunosuppressedsubjects. Since then, there have been sporadiccase reports of ABS worldwide.3-7 ABS can alsooccur in healthy individuals. In our cohort of ABSpatients prior exposure to antibiotics was universal.Antibotics can alter the gut microbiome allowingfungal elements to proliferate.8,9 Nonetheless, thiscondition has continued to be regarded as a mythPRACTICAL GASTROENTEROLOGY JULY 2021
Auto-brewery Syndrome: A Schematic for Diagnosis and Appropriate TreatmentNUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #212due to limited knowledge on the subject. Initially,only fungi were implicated in the conversion ofcarbohydrate to alcohol, but a recent large Chinesestudy also identified certain species of high alcoholproducing bacteria (e.g., Klebsiella species).10PathophysiologyAlthough the initiating or triggering factorsresulting in ABS remain uncertain, we proposethe following in its causation:1. Alteration of the gut microbiome: Thedisruption of gut homeostasis resulting inovergrowth of fungi, and in rare cases, highalcohol-producing bacteria (e.g., Klebsiellaspecies).1,10 All of our patients had priorexposure to antibiotics before developingABS symptoms.2. Fungal fermentation: Commercially,Saccharomyces cerevisiae (i.e., brewer’syeast) has been used for manufacturing beerfor centuries.11Risk FactorsIn our ABS cohort of patients, the most commonrisk factor for its causation has been prior useof antibiotics. Antibiotics may have disruptedthe fine homeostatic balance and symbioticrelationship between the different types of gutmicrobiota causing yeast overgrowth. Severalpatients with diabetes, short bowel syndrome,intestinal bacterial overgrowth, and inflammatorybowel disease (Crohn's disease with strictures),have also been described with ABS. Healthypatients may also suffer from ABS if exposed toa precipitating cause.1,4,5-7,12 It is uncertain if anygenetic components could have predisposed thesepatients to ABS.SymptomsPatients with ABS are known to present withsigns and symptoms of inebriation. Some withpsychiatric symptoms (i.e. altered mood, anxiety,dysphoria, changes in affect and depression) orneurological symptoms (i.e. changes in mentalstatus, drowsiness, brain fog, seizures, and ataxia).The patients can also have the smell of alcoholon their breath. The effects of alcohol are thesame regardless of whether it is endogenously orPRACTICAL GASTROENTEROLOGY JULY 2021 exogenously derived, and can increase the riskof fatty liver, cirrhosis of the liver and acute orchronic pancreatitis.10 The legal limit for drivingwhile intoxicated (DWI) is 0.08% in New Yorkand many other states. We have encountered manypatients with ABS with 3-4 times this level. Thesesymptoms could also overlap with those of chronicfatigue syndrome, depression, and alcoholismitself.DiagnosisUsually, these patients are either identified by aconcerned family member or had been arrestedfor alleged “DWI”. Identifying these patients isdifficult as ABS symptoms could masquerade asother entities. The medico-legal implications ofDWI are self-evident. When investigating a patientwith possible ABS, a complete medical history anda physical examination should be augmented withinterrogation of family and friends as they mayprovide additional vital information. The patientcan develop “memory fog” and therefore mighthave poor recall of past events. Particular attentionshould be paid to the onset of the condition, incitingfactors, prior antibiotic use, mold exposure, andany other useful information available fromtheir previous evaluations. Needless to say, thepresent or past detailed history of alcohol intakeis mandatory, including asking when the patientlast drank alcohol, if at all.Basic laboratory tests, i.e. complete blood count,comprehensive metabolic panel, and stool testingshould be performed to rule out other medicalconditions (e.g. diabetes, immunosuppression,leukopenia). It is also important to ascertain that thepatient is not surreptitiously drinking. Therefore,ideally the validity of the patient’s denial of alcoholconsumption has to be corroborated by a familymember or a friend. The diagnosis of ABS canonly be considered after other conditions whichmay present with similar symptoms have beenruled out. These patients are advised to purchase abreathalyzer and keep a log of their breathalyzermeasured breath alcohol content (BAC) morningand evening, and at any time when they aresymptomatic. Any positive level of breathalyzerBAC measurement needs to be confirmed with aconcomitant blood alcohol level and the patient’sphysician should also be immediately informed.11
Auto-brewery Syndrome: A Schematic for Diagnosis and Appropriate TreatmentNUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #212Suspected ABSDetailed historyand physicalexaminationPositive breathand bloodalcohol levelsBasicLaboratorytestingEndoscopy forgut visualizationand obtaininggut secretionsCarbohydrateChallengetesting forconfirmation ofABSTreatment ofABSFigure 1. Stepwise Diagnostic Evaluation for Auto-Brewery SyndromeJust prior to the carbohydrate challenge test,we initially perform upper and lower endoscopyto obtain gastric, upper small bowel, terminal ileal,and colon secretions. These samples are then testedfor pH, gram strain, culture, and antibiotic andantifungal sensitivity in a commercial laboratory.Once a particular fungal species is identified,further antifungal sensitivity testing is conductedto determine the appropriate choice of subsequenttherapy. The stepwise process for ABS diagnosisis summarized in Figure 1.The carbohydrate challenge test should beperformed when the patient’s breath and bloodalcohol levels are zero. If elevated, the patient willhave to wait until it becomes zero prior to testing.Patients have to be under complete observation withno access to alcohol along with zero initial bloodalcohol level in order for this test to be performed. Adiagnostic standardized carbohydrate challenge testwas performed after upper and lower endoscopicevaluation. This test consisted of administering200g of glucose orally in a supervised setting in anisolation room and testing both breath and bloodalcohol levels at baseline (0) and at 0.5, 1, 2, 4, 8hours after glucose administration. Patient wereallowed to eat any meal of their choice after theingestion of 200g of oral glucose. If alcohol levelsare elevated at any time during this evaluation,the test is aborted and considered to be positive.Patients who are still negative at 8 hours are giventhe option to return for a collection of a 16- and24-hour sample as some fungi can take longer12 than 8 hours to ferment carbohydrate. Therefore,a negative 8 hour test cannot exclude this diagnosisdue to some fermentation occurring even after 24hours.Testing a stool sample can assist in thescreening process, but the lower gastrointestinaltract can contain small amounts of fungalcolonization which would be considered normaland fermentation here would have little clinicalsignificance. Upper gastrointestinal tract fungalcolonization is significant, as the presence of fungiis considered pathological in this location. All ofthe patients who are currently under treatmentfor ABS had a positive carbohydrate challengetest and positive stool mycological studies on gutsecretions.PRACTICALGASTROENTEROLOGYVisit our Website:practicalgastro.comPRACTICAL GASTROENTEROLOGY JULY 2021
Auto-brewery Syndrome: A Schematic for Diagnosis and Appropriate TreatmentNUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #212Carbohydrate-freedietAntifungal therapyUse of Probiotic(Lactobiliusacidophilus)Figure 2. Algorithm for the Treatment of AutoBrewery SyndromeUntil now there had been no known standardizedscreening test for ABS. Therefore sensitivity and/or specificity of this test is unstudied. We are thefirst to propose a carbohydrate challenge test toidentity ABS patients. If BAC or blood alcohol isnegative, it is unlikely to see a positive carbohydratechallenge test, even if there is a strong suspicionfor ABS. When this carbohydrate challenge testis accepted and used more widely, we would havea better idea of the sensitivity, specificity andvalidity of this test. In our literature review, wehave found less than 100 cases since 1952. Weare now studying these patients and might be ableprovide more statistical information in the future.TreatmentThe same initial treatment protocol used forexogenous alcohol intoxication should be usedto treat ABS patients as well. This would includeadministering appropriate intravenous fluidsfor hydration, maintaining a clear airway, andcorrecting calorie and nutritional deficiencies(folate and thiamine). Alcohol withdrawalsymptoms if present should also be managed withbenzodiazepines. After the resolution of the patient’sacute symptoms and stabilization of the patient’scondition, targeted treatment for the patient’s ABScan be initiated. An interdisciplinary approach isstrongly recommended in these situations with theassistance of a Gastroenterologist, Psychiatrist andNutritionist for optimal care. The mainstay of ourdietary treatment should be to keep the patientPRACTICAL GASTROENTEROLOGY JULY 2021 initially on a carbohydrate free diet for 6 weeks ascarbohydrate is the only substrate that is convertedto alcohol by fungi. Otherwise, these patients areat liberty to ingest any non-carbohydrate meal. Atotal elimination of carbohydrate is difficult to topractice. We allowed small amounts of carbohydratefound in fruits or vegetables to be acceptable.Antifungal sensitivity testing should be done onany fungal strains isolated from the gastrointestinalsecretions to determine the appropriate choice ofantifungal treatment. We used nystatin as a firstline treatment when appropriate, as it has the leastamount of side effects and an established safetyrecord. Oral azole compounds (e.g., fluconazoleand itraconazole) are our next drugs of choiceif the patient is still symptomatic with elevatedbreath and blood alcohol levels while on nystatintherapy. Finally, intravenous micafungin is usedfor treatment failure.In addition to antifungal therapy, these patientsare started on a single strain probiotic (Lactobacillusacidophilus). Patients should continue to check theirBAC twice a day during, and after the 6 weeks ofantifungal treatment, and inform their physicians ofany positive results. After successfully completingthe 6-week therapy if the patient is asymptomaticwith negative BAC, the antifungal therapy isgradually tapered during the next 6 weeks andthen discontinued. We continued treatment withthe probiotic long-term. It would be ideal to havethe patient repeat the carbohydrate challenge testprior to reintroducing carbohydrate in their dietif feasible. If this test is positive then the patientwould require further antifungal therapy.Additionally, the role of probiotic use in ABSneeds to be fully investigated. Probiotic strainsof Lactobacillus have been studied and foundto have inhibitory effects on biofilm formationand filamentation in Candida albicans species.This probiotic has also previously been shownto competitively inhibit gut fungal growth inpatients.8,13-15 We had previously postulated thatfecal microbiome transplant might be valuablein ABS patients. There has only been a singlesuccessful report of using fecal microbiometransplant for the treatment of ABS in Belgium. Weawait further studies on this treatment modality.17See Figure 2 for proposed treatment algorithm.(continued on page 20)13
Auto-brewery Syndrome: A Schematic for Diagnosis and Appropriate TreatmentNUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #212#212(continued from page 13)CONCLUSIONABS is a rare and underdiagnosed medical conditionwhere ingested carbohydrate is converted to alcoholby fermentation in the gut. This condition shouldbe considered in any patient who has signs andsymptoms of inebriation despite denying alcoholintake. This syndrome has been described in themedical literature for over 50 years, but it stillremains a condition with limited informationregarding diagnosis and treatment. If a physiciansuspects that a patient has ABS, breathalyzeranalysis during the symptomatic episodes couldhelp the clinician determine if this condition mightbe present. We propose a standardized carbohydratechallenge test to screen patients with suspecteddiagnosis of ABS. While a positive test is veryuseful in detecting patients with ABS, a negative testdoes not definitively rule out ABS, as fungi couldtake longer than 24 hours to convert carbohydrateto alcohol. The seminal NIH microbiome studyfrom 2007 using genetic methodology has foundmany fungi are undetected by our usual commerciallaboratory culture techniques.15,17 As more researchemerges on the gut microbiome, it is hoped that abetter understanding of this medical condition willensue.References1.2.3.4.Ladkin RG, Davies JNP. Rupture of the stomach in anAfrican child. Br Med J. Br Med J. 1948 Apr 3;1(4552):644.Iwata K. A review of the literature on drunken syndromesdue to yeasts in the gastrointestinal tract. Tokyo, Japan:University of Tokyo Press; 1972.Hafez EM, Hamad MA, Fouad M, et al. Auto-brewerysyndrome: ethanol pseudo-toxicity in diabetic and hepaticpatients. Hum Exp Toxicol. 2017;36:445–50.Welch BT, Coelho Prabhu N, Walkoff L, et al. Auto-5.6.7.8.9.10.11.12.13.14.15.16.17.brewery syndrome in the setting of long-standing Crohn’sdisease: a case report and review of the literature. J CrohnsColitis. 2016;10:1448–50.Spinucci G, Guidetti M, Lanzoni E, et al. Endogenous ethanol production in a patient with chronic intestinal pseudoobstruction and small intestinal bacterial overgrowth. Eur JGastroenterol Hepatol. 2006;18:799–802.Green AD, Antonson DL, Simonsen KA. Twelve-year-oldfemale with short bowel syndrome presents with dizzinessand confusion. Pediatr Infect Dis J. 2012;31(4):425.Jansson-Nettelbladt E, Meurling S, Petrini B, et al.Endogenous ethanol fermentation in a child with shortbowel syndrome. Acta Paediatr. 2006;95:502–4.Malik F, Wickremesinghe P, Saverimuttu J. Case reportand literature review of auto-brewery syndrome: probably an underdiagnosed medical condition. BMJ OpenGastroenterol. 2019;6:e000325.Painter K, Cordell BJ, Sticco KL. Auto-brewery syndrome(Gut fermentation) [updated 2020 Jun 26]. In: StatPearls[Internet]. Treasure Island, FL: StatPearls Publishing; 2020Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513346/Yuan J, Chen C, Cui J et al. Fatty liver disease causedby high-alcohol-producing Klebsiella pneumoniae. CellMetabolism. 2019;30:675–88.e7.Walker GM, Stewart GG. Saccharomyces cerevisiae in theproduction of fermented beverages. Beverages. 2016;2:30.Tameez Ud Din A, Alam F, Tameez-Ud-Din A, et al.Auto-brewery syndrome: a clinical dilemma. Cureus.2020;12:e10983.Cordell B, McCarthy J. A case study of gut fermentationsyndrome (auto-brewery) with Saccharomyces cerevisiaeas the causative organism. Int J Clin Med. 2013;04:309–12.Suez J, Zmora N, Zilberman-Schapira G, et al. Postantibiotic gut mucosal microbiome reconstitution isimpaired by probiotics and improved by autologous FMT.Cell. 2018;174(6):1406-1423.e16.Vilela SFG, Barbosa J, Rossoni R, et al. Lactobacillusacidophilus ATCC 4356 inhibits biofilm formation by C.albicans and attenuates the experimental candidiasis inGalleria mellonella. Virulence. 2016;6:29–39.Vandekerckhove E, Janssens F, Tate D, et al. Treatment ofgut fermentation syndrome with fecal microbiota transplantation. Ann Intern Med. 2020;173(10):855.Sam QH, Chang M, Chai L, et al. The fungal mycobiomeand its interaction with gut bacteria in the host. Int J MolSci. Y46Years19 7 720 PRACTICAL GASTROENTEROLOGY JULY 2021
1. Alteration of the gut microbiome: The disruption of gut homeostasis resulting in overgrowth of fungi, and in rare cases, high alcohol-producing bacteria (e.g., Klebsiella species).1,10 All of our patients had prior exposure to antibiotics before developing ABS symptoms. 2. Fungal fermentation: Commercially, Saccharomyces cerevisiae (i.e .
Revenge of the Cyst –Part II NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #55 Joe Krenitsky, MS, RD, Nutrition Support Specialist; Diklar Makola, MD, MPH, PhD, Gastroen-terology Fellow; Carol Rees Parrish MS, RD, Nutrition Support Specialist all at Digestive Health Center of Excellence, University of Virginia Health System, Charlottesville, VA.
Parrish Village News. page 2 Parrish Village News Official publication of the Parrish Civic Association, a non profit coporation. P. O. Box 257 Parrish, FL 34219
popularized the SCD in her book, Breaking the Vicious Cycle: Intestinal Health Through Diet. The SCD can be well balanced, but is very specific in the types of sugars and starches that are allowed (Table 1). The natural SCD aims to permit single sugars, or monosaccharides, such as those found in some fruits, certain vegetables, and
Enhanced Recovery After Surgery (ERAS) and Immunonutrition: An Evidence-Based Approach 2. Dietitian referral with a positive screen. 3. Lean body mass evaluation by CT if available. 4. Oral nutritional supplements (ONS) for "at risk" patients (either high in protein or IMN). 5. Placement of a home feeding tube for
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WEST COAST HOTEL CO. v. PARRISH. 379 Syllabus. WEST COAST ttOTEL CO. v. PARRISH ET AL. APPEAL FROM THE SUPREME COURT OF WASHINGTON. No. 293. Argued December 16, 17, 1936.-Decided March 29, 1937. 1. Deprivation of liberty to contract is forbidden by the Constitution if without due process of law; but restraint or regulation of this .
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