Gut Microbial Urease Activity Drives Hyperammonemia and Predicts Overt Hepatic Encephalopathy in Cirrhosis.

Area of Science:

• Gastroenterology and Hepatology
• Microbiology
• Metabolic Disorders

Background:

• Hyperammonemia is central to overt hepatic encephalopathy (OHE) development and prognosis.
• Ammonia is produced in the gut by bacterial urease and cleared by the liver.
• The role of gut microbial urease activity in ammonia metabolism and OHE requires further investigation.

Purpose of the Study:

• To investigate the relationship between gut microbial urease activity, ammonia metabolism, and OHE in cirrhosis.
• To assess stool urease activity (SUA) as a predictor of new-onset OHE in patients with cirrhosis.

Main Methods:

• Experimental cirrhosis models in rats were used to study ammonia metabolism and SUA.
• Rats were gavaged with urease-positive bacteria (Klebsiella pneumoniae) to assess its impact on SUA and ammonia levels.
• Baseline SUA and plasma ammonia were measured in cirrhosis patients and healthy controls, with a 3-month follow-up to monitor OHE development.

Main Results:

• Cirrhotic rats showed significantly elevated SUA and plasma ammonia compared to controls.
• Gavage with Klebsiella pneumoniae increased SUA and ammonia levels in cirrhotic rats.
• Cirrhosis patients exhibited higher SUA and plasma ammonia than controls; SUA was a better predictor of OHE than plasma ammonia.

Conclusions:

• Gut urease activity directly contributes to elevated plasma ammonia levels in cirrhosis.
• Increased stool urease activity (SUA) is a promising biomarker for predicting new-onset overt hepatic encephalopathy in cirrhosis patients.