Gut microbial community in depressed mice treated with engineered EcN

This work engineers Escherichia coli Nissle 1917 with high 5-HTP production capacity via a genetic code expansion-based high-throughput screening method. After systematic enzyme-directed evolution and gene editing, the most robust strain EcN@5-HTP with a yield of 387.1 mg/L 5-HTP is obtained. When used as a live therapeutic, EcN@5-HTP exhibits strong antidepressant efficacy in mice, and the underlying mechanisms involve improving the 5-HT levels in the gut and brain, repairing neurological abnormalities, suppressing inflammation, elevating SCFAs concentrations, and modulating gut microbiota dysbiosis.