Synthetic biology in probiotic lactic acid bacteria: At the frontier of living therapeutics.

The trillions of microbes hosted by humans can dictate health or illness depending on a multitude of genetic, environmental, and lifestyle factors that help define the human ecosystem. As the human microbiota is characterized, so can the interconnectivity of microbe-host-disease be realized and manipulated. Designing microbes as therapeutic agents can not only enable targeted drug delivery but also restore homeostasis within a perturbed microbial community. Used for centuries in fermentation and preservation of food, lactic acid bacteria (LAB) have a long history of safe, and occasionally health promoting, interactions with the human gut, making them ideal candidates for engineered functionality. This review outlines available genetic tools, recent developments in biomedical applications, as well as potential future applications of synthetic biology to program LAB-based therapeutic systems.