National University of Singapore engineers living medicine to treat brain dysfunction by reprogramming gut bacteria

Singaporean scientists develop programmable gut bacteria that reduce ammonia and restore brain function in patients with severe liver-related dysfunction.

By: AXL Media

Published: Apr 29, 2026, 7:40 AM EDT

Source: Information for this report was sourced from EurekAlert!

Engineering a Novel Solution for Hepatic Encephalopathy

A significant advancement in synthetic biology has emerged from the National University of Singapore (NUS), where scientists have successfully reprogrammed a common gut bacterium to treat liver-related brain dysfunction. Hepatic encephalopathy (HE) occurs when a failing liver cannot filter toxins like ammonia, allowing them to reach the brain and cause symptoms ranging from memory loss to coma. Led by Professor Matthew Chang, the research team redesigned Lactobacillus plantarum WCFS1 into a "living medicine" capable of addressing the metabolic imbalances that drive this condition. Published in the journal Cell, the study represents a shift from traditional chemical pharmacology to precision biological therapeutics.

A Dual-Strain Approach to Metabolic Restoration

The therapeutic platform consists of two complementary strains of engineered bacteria that work in tandem within the digestive tract. The first strain is designed to absorb excess ammonia from the gut and convert it into branched-chain amino acids, which are essential nutrients typically depleted in patients with chronic liver disease. The second strain targets L-glutamine, breaking it down before it can be processed into additional ammonia. This dual-action mechanism effectively cuts off the primary source of neurotoxicity while simultaneously replenishing the body’s nutrient reserves. In laboratory settings, this bacterial cocktail reduced circulating ammonia by up to 10-fold, bringing brain ammonia levels back to a healthy range.

Outperforming Conventional Antibiotic Treatments

The NUS study highlights several distinct advantages of living biotherapeutics over rifaximin, the current front-line antibiotic for HE. While rifaximin broadly suppresses gut bacteria to reduce ammonia production, it often disrupts the natural microbiome and offers only partial relief from neurological symptoms. In contrast, the engineered bacterial cocktail normalized neuronal signaling and significantly reduced neuroinflammation. Furthermore, the living medicine achieved superior results in improving anxiety and short-term memory function. Because the engineered strains are designed to work alongside the existing microbial ecosystem, they maintained the natural diversity of the gut, avoiding the "scorched earth" effect of traditional antibiotics.