Intestinal Engineered Probiotics as Living Therapeutics: Chassis Selection, Colonization Enhancement, Gene Circuit Design, and Biocontainment

Intestinal probiotics are often used for the in situ treatment of diseases, such as metabolic disorders, tumors, and chronic inflammatory infections. Recently, there has been an increased emphasis on intelligent, customized treatments with a focus on long-term efficacy; however, traditional probiotic therapy has not kept up with this trend. The use of synthetic biology to construct gut-engineered probiotics as live therapeutics is a promising avenue in the treatment of specific diseases, such as phenylketonuria and inflammatory bowel disease. These studies generally involve a series of fundamental design issues: choosing an engineered chassis, improving the colonization ability of engineered probiotics, designing functional gene circuits, and ensuring the safety of engineered probiotics. In this review, we summarize the relevant past research, the progress of current research, and discuss the key issues that restrict the widespread application of intestinal engineered probiotic living therapeutics.