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Bladder and gut fermentation syndromes: Unusual disorders with significant implications

In a recent review published within the journal BMI Medicine, researchers reviewed existing data on bladder fermentation syndrome (BFS) pathophysiology, diagnosis, treatment, and significance in comparison with gut fermentation syndrome (GFS).



BFS and GFS are unusual medical disorders that may result in ethanol intoxication in individuals with poorly managed diabetes. The absence of alcoholic intoxication because of the bladder lumen’s transitional epithelium distinguishes BFS. GFS patients can experience symptoms even without consuming alcohol because of alcoholic fermentation within the gut lumen. Yeast removal, antifungals or antibiotics, and changes to the underlying problems can treat each disorders. Nonetheless, failing to acknowledge these aspects may need grave legal implications.

In the current review, researchers examined the etiology, clinical characteristics, and diagnostic techniques of BFS and compared them to GFS.

Gut and bladder fermentation syndromes: a narrative review. Image Credit: Magic mine / Shutterstock

BFS: Introduction, pathophysiology, diagnosis, and treatment

BFS is a syndrome characterised by ethanol production within the urinary bladder of people with poorly managed diabetes. The primary clinical occurrence of BFS occurred in 2020, and the patient failed abstinence monitoring. In 2020, researchers published the primary experimentally proven example of ethanol fermentation within the bladder with ethanol produced by Candida glabrata. In BFS, the shortage of alcoholic intoxication is critical for the reason that bladder lumen comprises transitional epithelium with limited ethanol permeability.

Funguria is the presence of yeast, mainly Candida species, in urine because of yeast colonization within the bladder or widespread candidiasis. Funguria is frequent amongst older hospitalized patients, and Candida albicans is the predominant etiological organism. Alcoholic fermentation is a metabolic process occurring after glycolysis, allowing yeast species to replenish nicotinamide adenine dinucleotide (NAD) in anaerobic conditions. In cases of oxygen insufficiency for energy synthesis, crabtree-positive yeast, reminiscent of C. glabrata, initiate glycolysis or alcoholic fermentation.

Simplified biochemical pathways illustrating glycolysis, alcoholic fermentation, and the TCA cycle in Crabtree-positive yeast. In Crabtree-positive yeast such as Candida glabrata, glucose is preferentially metabolized through glycolysis and alcoholic fermentation to ethanol in the cytosol without utilizing oxygen in the TCA cycle in mitochondria (shown in grey in the figure), even in the presence of oxygen in the surrounding environment as in the bladder lumen. In alcoholic fermentation, pyruvate is decarboxylated into acetaldehyde by pyruvate decarboxylase ①, and acetaldehyde is further metabolized to ethanol by alcohol dehydrogenase ②. TCA, tricarboxylic acid

Simplified biochemical pathways illustrating glycolysis, alcoholic fermentation, and the TCA cycle in Crabtree-positive yeast. In Crabtree-positive yeast reminiscent of Candida glabrata, glucose is preferentially metabolized through glycolysis and alcoholic fermentation to ethanol within the cytosol without utilizing oxygen within the TCA cycle in mitochondria (shown in grey within the figure), even within the presence of oxygen in the encircling environment as within the bladder lumen. In alcoholic fermentation, pyruvate is decarboxylated into acetaldehyde by pyruvate decarboxylase ①, and acetaldehyde is further metabolized to ethanol by alcohol dehydrogenase ②. TCA, tricarboxylic acid

BFS patients don’t experience alcohol intoxication symptoms since their bladder wall’s transitional epithelia operate as a low-permeability barrier for water and tiny molecules reminiscent of ethanol. Laboratory identification of yeast species and antifungal susceptibilities can aid in diagnosing and treating BFS. In BFS instances, ethanol metabolites are absent, requiring more precise experiments and test batterie to substantiate the diagnosis.

BFS therapy entails managing hyperglycosuria and maybe removing fermenting yeast from the bladder. Lowering urine glucose levels can slow fermentation and reduce the possibility of creating yeast colonies. Antidiabetic medications like dapagliflozin might increase glucose excretion and worsen BFS. Yeast colony elimination may require antifungal medications. Nonetheless, S. cerevisiae and C. glabrata form biofilms that may impart resistance to the azole class of medication. Monitoring alcohol abstinence is important in addiction management, driver’s license trials, driving under the influence (DUI) -type programs, and hepatic transplant assessments.

Pathophysiology of bladder fermentation syndrome and gut fermentation syndrome. a In bladder fermentation syndrome, ethanol produced through alcoholic fermentation by Crabtree-positive yeast is urinary-eliminated without getting absorbed into systemic circulation because the transitional epithelium in the urinary bladder serves as a barrier to ethanol. b In gut fermentation syndrome, ethanol produced through alcoholic fermentation by yeast and/or bacteria is absorbed into systemic circulation through the columnar epithelium in the intestine, causing alcohol intoxication. A dysfunctional gut barrier caused by dysbiosis and ethanol may also be involved in its pathogenesisPathophysiology of bladder fermentation syndrome and gut fermentation syndrome. a In bladder fermentation syndrome, ethanol produced through alcoholic fermentation by Crabtree-positive yeast is urinary-eliminated without getting absorbed into systemic circulation since the transitional epithelium within the urinary bladder serves as a barrier to ethanol. b In gut fermentation syndrome, ethanol produced through alcoholic fermentation by yeast and/or bacteria is absorbed into systemic circulation through the columnar epithelium within the intestine, causing alcohol intoxication. A dysfunctional gut barrier attributable to dysbiosis and ethanol can also be involved in its pathogenesis

A comparison of BFS and GFS

GFS is an unusual medical syndrome during which individuals experience symptoms of ethanol intoxication without having consumed alcohol. Alcoholic fermentation within the gut lumen causes GFS. GFS patients may fail abstinence regulation because of positive ethanol blood tests, putting them in danger for alcohol-related illnesses. GFS is comparable to BFS, nevertheless it necessitates a radical diagnostic evaluation and therapy, which incorporates a carbohydrate challenge test. Treatment consists of addressing underlying problems, removing fermenting bacteria, and adding carbohydrate-reduced diets and probiotics. Untreated BFS patients may develop repeated acute ethanol intoxication without drinking or spontaneous inebriation.

BFS and GFS are two different conditions defined by alcohol toxicity. Despite considerable ethanol levels within the urinary bladder, BFS patients don’t show alcohol presence of their blood and don’t exhibit intoxication symptoms, rendering them asymptomatic and unnoticed. GFS patients, then again, might acquire alcohol intoxication without consuming any alcohol, which could lead to legal implications like DUI. GFS victims can also fail abstinence testing and seek medical attention.

Disordered microbiota in hole organs, leading to ethanol fermentation by yeast within the stomach and bladder, cause BFS and GFS. Poorly managed diabetes, leading to hyperglycosuria, often causes BFS. In contrast, GFS instances often occur in individuals with underlying health conditions inducing gut microbial dysbiosis, like Crohn’s disease, post-surgical short gut syndrome, and up to date antibiotic usage. Fermenting yeast causes most GFS instances, although antifungal-resistant GFS related to Klebsiella pneumoniae, a yeast that produces alcohol in large quantities, has occurred.

Based on the review findings, BFS and GFS are unusual medical disorders ceaselessly misconstrued because of their comparable etiology, clinical characteristics, and diagnostic testing. The under-recognition of those circumstances might result in incorrect interpretations of abstinence monitoring, thereby stopping patients from getting medical therapy, reminiscent of transplantation. A primary reason behind this underrecognition is a scarcity of scientific data on yeast and bacterial fermentation within the body. Future research should consider determining the pathogenic functions of fermenting microbes in each illnesses, promoting awareness, and possibly clarifying terminology to enhance medical professionals’ comprehension.

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