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"Shield" Armed Programmable Probiotics Harboring α-Aminoadipate Aminotransferase Gene Regulate Tryptophan Metabolism
Aijiang Liu1,2, Jun Ma2, Zengguang Liu2
1Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130012, China.
Abstract:
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 However, this concept is considered outdated due to its restricted efficacy and unavoidable side effects.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.
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