Ammonia handling in the gut–liver axis

Ammonia handling in the gut–liver axis is a complex physiological process essential for maintaining systemic ammonia homeostasis and preventing neurotoxicity (MDPI, 2024). Ammonia is primarily produced in the gastrointestinal tract through the action of bacterial ureases on urea and the deamination of glutamine by enterocytes (NIH, 2019). This gut-derived ammonia is transported via the portal vein to the liver, where it is detoxified through the urea cycle or converted into glutamine by glutamine synthetase (MDPI, 2024). Dysregulation of this axis, common in liver cirrhosis and urea cycle disorders, leads to hyperammonemia, which is a primary driver of hepatic encephalopathy (Cochrane, 2019). Therapeutic strategies focus on reducing ammonia production in the gut using non-absorbable disaccharides like lactulose or antibiotics like rifaximin (NIH, 2025). Additionally, ammonia scavengers such as sodium phenylbutyrate and amino acid supplements like L-ornithine L-aspartate are used to enhance systemic ammonia clearance (NIH, 2019). Emerging therapies also explore modulating the gut microbiota through probiotics and fecal microbiota transplantation to restore axis balance (NIH, 2025). Monitoring blood ammonia levels and psychometric performance remains standard for assessing the efficacy of treatments targeting this axis (ResearchGate, 2026).

Other names

Enterohepatic ammonia metabolismGut-liver ammonia axisAmmonia detoxification pathway

Therapeutic agents target the gut–liver axis by reducing intestinal ammonia production (e.g., through bacterial urease inhibition or altering gut pH), decreasing ammonia absorption, or enhancing hepatic and systemic ammonia detoxification via the urea cycle and glutamine synthesis pathways (NIH, 2025; MDPI, 2024).