Oral delivery of bacteria: Basic principles and biomedical applications

Bacterial therapy, which presents a smart platform for delivering and producing therapeutic agents, as monotherapy or in combination with other therapeutic modes, has provided a breakthrough for the treatment of a range of diseases. The integration of synthetic biology technology with bacteria enables their characteristics like chemotaxis and biomolecule secretion to outperform conventional diagnostics and therapeutics, thereby facilitating their clinical applications in a range of diseases. Compared to injection-administered bacteria, orallydelivered bacteria improve patient compliance while avoiding the risk of systemic infections. However, oral administration of microbes always leads to a substantial loss of viability due to the highly acidic environment in the stomach and bile salt in the intestine. Thus, the formulation of these bacteria into microcapsules using appropriate biomaterials is a promising approach for reducing cell death during gastrointestinal passage and controlling the release of these therapeutic cells across the intestinal tract. In this review, we reveal the basic principles of oral bacterial delivery, from internal genetic engineering approaches to external encapsulation and modification, and summarize the most recent biomedical applications. Finally, we discuss future trends in oral bacterial therapy as well as current challenges that need to be resolved to advance their clinical applications.