The article details the development of genetically engineered bacteria designed to treat hepatic encephalopathy (HE) by correcting metabolic imbalances within the gut-liver-brain axis. Scientists modified the commensal strain Lactobacillus plantarum to simultaneously consume toxic ammonia, utilize L-glutamine, and produce essential branched-chain amino acids (BCAAs). In preclinical mouse models, oral administration of these "live biotherapeutics" successfully reduced systemic and brain ammonia levels while improving cognitive function and anxiety-like behaviors. Transcriptomic analysis further revealed that the treatment restored neuronal signaling and lowered brain inflammation more effectively than the standard antibiotic therapy, rifaximin. Significantly, these engineered strains preserved natural gut microbiota diversity and were safely eliminated from the body once dosing concluded. This study highlights the potential of programmable probiotics as a sophisticated platform for managing complex metabolic and neurological disorders.

References:

• Aggarwal N, Shen H, Lee L T, et al. Engineered commensals for metabolic modulation of the gut-liver-brain axis[J]. Cell, 2026.