Abstract
The oral delivery of macromolecules is quite challenging due to environmental insults and biological barriers encountered along the gastrointestinal (GI) tract. Benefiting from their living characteristics, diverse bacterial species have been engineered as intelligent platforms to deliver various therapeutics. To tackle difficulties in oral delivery, innovative bacteria-based microdevices have been developed by virtue of advancements in synthetic biology and nanotechnology, with aims to overcome the instability and short half-life of macromolecules in the GI tract. In this review, we summarize the main classes of macromolecules that are produced and delivered through the oral ingestion of bacteria and bacterial derivatives. Furtherly, we discuss the engineering strategies and biomedical applications of these living microdevices in disease diagnosis, bioimaging, and treatment. Finally, we highlight the advantages as well as the limitations of these engineered bacteria used as platforms for the oral delivery of macromolecules and also propose their potential for clinical translation. The results summarized in this review article would contribute to the invention of next-generation bacteria-based systems for the oral delivery of macromolecules.