Treatment of Gut Fermentation Syndrome With Fecal Microbiota Transplantation

Treatment of Gut Fermentation Syndrome With Fecal Microbiota Transplantation Background: Gut fermentation syndrome, also known as auto-brewery syndrome, is a rare condition in which endogenous ethanol production in the gut after carbohydrate-rich meals leads to elevated blood alcohol levels, a feeling of drunkeness, variably disturbed liver function, and other indications of ethanol intoxication. Most reports have assumed that the mechanism of ethanol production involves carbohydrate fermentation by excessive fungal growth in the gut (1, 2). Objective: To report what we believe is the first successful treatment of a patient with chronic gut fermentation syndrome by using fecal microbiota transplantation. Case Report: In 2016, we cared for a 47-year-old man who had intermittent episodes of feeling drunk during the previous 2 months. These symptoms started 1 month after 2 consecutive courses of amoxicillin–clavulanic acid and moxifloxacin for a respiratory tract infection. The patient was a social drinker, with a maximum weekend intake of 5 to 6 units of alcohol (1 unit = 10 mL or 8 g of pure alcohol). He said that he had not consumed any alcohol for more than 4 days before coming to see us, but a blood sample obtained during the consultation showed an ethanol level of 34.7 mmol/L (normal, <2 mmol/L). Liver function tests showed a slightly increased level of aspartate aminotransferase (40 U/L [normal, 0 to 37 U/L]) and an elevation in -glutamyltransferase (334 U/L [normal, <64 U/L]). Serologic tests found no evidence of viral or immunologic causes of liver disease. Hepatic ultrasonography revealed hepatomegaly with moderate steatosis. The patient's daily medications were aspirin, 80 mg; phenytoin, 100 mg twice a day for epilepsy; and a 50-μg fentanyl patch every 3 days for low back pain. These findings, along with a history of Roux-en-Y gastric bypass surgery 14 years earlier, made us suspect gut fermentation syndrome. Upper gastrointestinal endoscopy showed a patent gastroenterostomy, and gastric biopsy results were negative for Helicobacter pylori. No dilated or blind intestinal loops were seen on imaging. A fecal culture identified Candida glabrata, which has been reported in other cases of gut fermentation syndrome. We administered a 100-g oral dose of glucose, and the patient's blood ethanol levels rose from zero to a maximum value of 8.9 mmol/L 4 hours later. We considered this information sufficient to establish the diagnosis of gut fermentation syndrome, and we started treatment with a low-carbohydrate diet combined with fluconazole, 100 mg/d orally for 3 weeks, followed by nystatin, 500 000 IU orally 4 times a day for another 4 weeks. Despite this treatment, the patient still felt inebriated, his wife said he had an ethanol odor, and he had a random blood ethanol level of 23.6 mmol/L despite recently abstaining from alcohol use. We then administered a total of 4 weeks of amphotericin B (oral suspension, 100 mg 4 times a day for 2 weeks, then 100 mg/d for another 2 weeks), but this treatment also seemed unsuccessful. After the patient lost his driving license in a random police check, we proposed a fecal microbiota transplantation. He gave informed consent, and his 22-yearold daughter volunteered to be the donor and satisfied guidelines for donation. In June 2017, we administered the fecal transplant into his jejunum. After 34 months, he remained free of symptoms, with repeatedly normal ethanol levels (<2 mmol/L) and normal liver function test results. He regained his driving license and occasionally drinks beer. Discussion: Even in healthy persons, blood ethanol levels may vary between 0 and 0.7 mmol/L, and higher levels are observed in patients with diabetes or cirrhosis (3). Factors that promote higher levels include gastrointestinal anatomy altered by abdominal surgery or strictures, which are thought to allow fungal or bacterial overgrowth. For example, this phenomenon has been observed in children with Crohn strictures or short bowel syndrome. In addition, recent antibiotic use is reported to be a possible cause of the change in gut microbiota that is thought to precede gut fermentation syndrome [4]. On the basis of our experience with this patient, we advise other clinicians who have patients with gut fermentation syndrome to consider treatment with fecal microbiota transplantation, especially if more traditional therapy has failed. Moreover, we can imagine a future point—after additional research to evaluate the safety of fecal microbiota transplantation—at which this approach might become standard therapy for gut fermentation syndrome.