Precision therapeutics for inflammatory bowel disease using engineered probiotics: Strategies and optimization

The incidence of inflammatory bowel disease (IBD) has been increasing annually, evolving into a global health concern. Dysbiosis of the gut microbiota plays a crucial role in the pathogenesis of IBD. Probiotics, capable of modulating the gut microbiota, enhancing intestinal barrier function, and regulating mucosal immunity, have recently emerged as potential complementary or alternative therapy for IBD. However, traditional probiotics are limited by the functional singularity of strains and non-targeted mechanisms of action, thus resulting in unstable efficacy and inter-individual variability in clinical IBD intervention. In contrast, engineered probiotics, achieved through genetic modification and synthetic biology, have enabled microenvironment responsiveness and precise therapeutic targeting of IBD, thus demonstrating significant therapeutic effects in intestinal mucosal repair and immune modulation. This review summarizes the research progress of engineered probiotics in treating IBD, covering gene editing strategies of chassis strains, the multi-dimensional roles of microorganisms in IBD treatment, bioengineering modifications, optimization of delivery systems, and artificial intelligence-driven strain screening and design. STATEMENT OF SIGNIFICANCE: Engineered probiotics represent a frontier in inflammatory bowel disease (IBD) therapy. Through genetic modification and synthetic biology, these improved strains exhibit targeted reactivity to the intestinal pathological microenvironment, demonstrating potent mucosal repair and immunomodulation. This review summarizes the recent research on engineered probiotics, including chassis strain gene editing strategies, the multi-dimensional role of the gut microbiota in IBD therapy, bioengineering modifications, delivery system optimization, and artificial intelligence-driven strain screening and design. It emphasizes their potential in enhancing therapeutic precision, safety, and personalization, thereby offering improved technological avenues for IBD treatment and providing crucial insights for researchers and clinicians to accelerate therapeutic innovation.