Engineered probiotics as live biotherapeutics for diagnosis and treatment of human diseases.

The use of probiotics to regulate the intestinal microbiota to prevent and treat a large number of disorders and diseases has been an international research hotspot. Although conventional probiotics have a certain regulatory role in nutrient metabolism, inhibiting pathogens, inducing immune regulation, and maintaining intestinal epithelial barrier function, they are unable to treat certain diseases. In recent years, aided by the continuous development of synthetic biology, engineering probiotics with desired characteristics and functionalities to benefit human health has made significant progress. In this article, we summarise the mechanism of action of conventional probiotics and their limitations and highlight the latest developments in the design and construction of probiotics as living diagnostics and therapeutics for the detection and treatment of a series of diseases, including pathogen infections, cancer, intestinal inflammation, metabolic disorders, vaccine delivery, cognitive health, and fatty liver. Besides we discuss the concerns regarding engineered probiotics and corresponding countermeasures and outline the desired features in the future development of engineered live biotherapeutics.