Toward a systematic design of smart probiotics

Abstract

Synthetic biology has been instrumental in turning microbes into cell-factories capable of diverse processes. A recent application has been to convert them into living therapeutics with diagnostic and production capabilities. These smart probiotics act as living medicines inside the body capable of diagnosing and responding to environmental cues in real time. Many companies and research groups have reported success with smart probiotics with several advancing to human clinical trials. Despite the promise, engineered probiotics are unable to replicate their functionality in a more complex environment. A rich environment, such as the gut, imposes restrictions on probiotic durability and effectiveness, hindering its ability to reach its full potential. Scientists have a plethora of advanced tools available today that enable enhanced strain engineering decisions to increase the production of fuels and commodity chemicals. However, these tools have not yet found mainstream application in building smart probiotics. Majority of the work in this field still relies on rational engineering. This review will propose strategies, with a focus on model-based approaches, that can help bridge the gap to systematic design and optimization of smart probiotics.