Living Microbial Drugs.

Living microbial therapeutics have arisen as a novel category of medications that extend beyond traditional small molecules and biologics. Advancements in synthetic biology have facilitated the rational engineering of microorganisms to detect host or disease-related signals and administer therapeutic chemicals in situ. In contrast to conventional pharmaceuticals, these live biotherapeutic agents engage in dynamic interactions with both the host and its microbiota, allowing context-specific, self-regulating therapies. This review emphasizes the progression of the field from conventional probiotics to advanced, designed living therapeutics. We examine principal microbiological platforms, including bacteria, yeasts, and alternative systems such as phages and archaea, delineating their relative benefits and constraints as therapeutic hosts. Key design principles, genetic logic circuits, quorum-sensing-based regulation, and synthetic memory devices that enable microorganisms to possess context-dependent and self-adjusting therapeutic capabilities, are discussed alongside present and emerging therapeutic applications in infectious diseases, metabolic disorders, inflammatory illnesses, and cancer immunotherapy, where engineered microorganisms have demonstrated significant preclinical effectiveness and first clinical promise. Despite these advancements, obstacles remain, including biosafety, biocontainment, regulatory approval, and patient acceptability. Engineered living microbial therapeutics signify a swiftly evolving domain in medicine, set to transform treatment paradigms via intelligent, flexible, and sustainable methodologies for human health.