“Shield” Armed Programmable Probiotics Harboring α-Aminoadipate Aminotransferase Gene Regulate Tryptophan Metabolism and Gut Microbiota to Alleviate the Inflammatory Bowel Disease

Current treatment of inflammatory bowel disease (IBD) relies on anti-inflammatory and immunosuppressive agents. However, this concept is considered outdated due to its restricted efficacy and unavoidable side effects. Herein, a polynorepinephrine-coated programmable probiotic expressing α-aminoadipate aminotransferase (NE-EcN-pA) was constructed to improve the levels of kynurenic acid and xanthurenic acid in the intestine by modulating the endogenous tryptophan metabolism. The NE layer could protect EcN-pA against the harsh environment of the gastrointestinal tract, enhancing its survival and colonization. In UC mice, oral administration of NE-EcN-pA effectively alleviated intestinal inflammation and restored the intestinal epithelial barrier owing to the activation of the aryl hydrocarbon receptor pathway. Furthermore, NE-EcN-pA promoted the diversity of intestinal flora, improved the imbalance of flora, and enhanced the content of short-chain fatty acids in the colon. Overall, NE-EcN-pA can regulate endogenous tryptophan metabolism and gut microbiota, showing promise in the treatment of gastrointestinal disorders.