Reprogramming Microbes for Disease Intervention & Prevention: Live Biotherapeutics for Microbiome Modulation

The wealth of knowledge on the human intestinal microbiota composition and its role in health and disease has spurred the development of novel therapeutic strategies that target the microbiota in recent years. Furthermore, with an array of genetic tools that are readily available, we can design and build genetic circuits, edit and rewrite genomes and reprogram cells, to foster novel microbiota-based interventions. Herein, we present our work that focuses on engineering gut-resident microbes to deploy targeted therapeutic functionalities, including the detection of health and disease biomarkers and physiological conditions, and the delivery of therapeutic molecules and enzymes. This conceptual approach of transforming gut microbes into live biotherapeutics with prophylactic and therapeutic efficacy has been demonstrated against opportunistic pathogens and chronic metabolic diseases such as cancer. This work provides a strong foundation in the application of engineered designer microbes for modulating microbiota-host metabolism and interactions and supports the use of functional microbes as a viable strategy for clinical intervention.