Bacteria-driven bio-therapy: From fundamental studies to clinical trials

Natural bacteria have been utilized to directly maintain the human body's homeostasis for directly or indirectly relieving diseases throughout history. With the rapid development of genetic engineering and synthetic materials modification, the recent era has witnessed numerous hybrid bacteria designed to meet the clinical requirements with expanded functionality in treating dozens of diseases, including obesity, gastrointestinal disorders, and even cancers. This review outlined the characteristics and applications of natural bacteria-based drugs in treating different disease conditions and summarized different conjugation methods of hybrid bacteria and their fate in vivo through multiple administration routes. Moreover, therapeutic bacteria-based complex disease treatments were also discussed to reveal the importance and feasibility of these biotherapeutics. Finally, the challenges in the clinical applications of bacterial drugs were discussed. The current review further highlighted the forward-looking solution strategies for bacterial bio-therapy to accelerate its clinical usage.