Engineered Bacteria as Living Materials for Oral Delivery of Peptide Drugs

Peptide drugs play a crucial role in treating numerous major diseases due to their high bioactivity, specificity, and biosafety. However, their oral delivery is severely limited by gastric acidity, enzymatic degradation, and poor intestinal absorption, leading to extremely low bioavailability. In recent years, bacterium has emerged as a promising drug delivery platform. Engineered bacteria can colonize the gastrointestinal tract, enabling in situ synthesis and release of therapeutic peptides, thereby offering an effective strategy to overcome the bottlenecks in oral peptide delivery. This review summarizes recent advances in engineered bacteria as "living functional materials" for oral peptide delivery, focusing on the optimization of chassis cells and the mechanisms of peptide release. It systematically outlines their therapeutic applications in metabolic, inflammatory, neurodegenerative diseases, and cancer. Finally, we discuss the emerging potential of intelligent engineered bacterial delivery systems to drive in situ peptide self-assembly, expanding the boundaries of biomaterials and supporting the development of next-generation smart, responsive, and programmable oral peptide delivery systems.