Microbial chassis selection for niche-specific engineered live biotherapeutics

The human microbiota comprises a vast and diverse array of microorganisms that play critical roles in maintaining health and modulating diseases. Engineered live biotherapeutic products (eLBPs) harness genetically modified microbes to perform defined therapeutic functions within the host. A central challenge in developing effective eLBPs is the rational selection of an appropriate microbial chassis, which requires consideration of safety, genetic tractability, functional performance and the target host niche. As different body sites present distinct physiological and biochemical conditions that influence microbial survival, colonisation and activity, choosing a chassis well-adapted to the target niche is essential for therapeutic durability and sustained efficacy. This review summarises microbial chassis that have been widely employed for the gut, skin, vagina and tumour microenvironment, highlighting how their characteristics enable effective function within these niches. Strategies to improve eLBP colonisation within these niches are discussed, and emerging microbial candidates that hold promise as future eLBPs are also identified.