Engineered Nissle 1917 Depletes Branched-Chain Amino Acids to Suppress Colorectal Tumorigenesis.

Colorectal cancer (CRC) is heavily influenced by gut microbiota and metabolites such as branched-chain amino acids (BCAAs), which provides essential growth materials for tumors and activates related cancer-promoting pathways. We engineered two Nissle 1917 strains (ECN)─ECN-Deg and ECN-Tra─to deplete BCAAs in the gut in previous work. In this work, using an AOM/DSS-induced CRC mouse model under the amino acid diet, we found that both strains significantly ameliorated CRC progression, improved survival, restored gut barrier function, and reduced systemic inflammation. Mechanistically, they lowered plasma BCAA levels, suppressed mTOR activation, and modulated retinol and drug metabolism pathways. Our results demonstrate that engineered probiotics targeting BCAAs catabolism can effectively inhibit colorectal tumorigenesis, offering a novel synthetic biology-based approach for cancer therapy.