Surface modification of probiotics at single-cell resolution: Strategies, applications, and future directions in inflammatory bowel disease

Inflammatory bowel disease (IBD) manifests as a chronic immune-mediated gastrointestinal disorder is characterized by multifactorial pathogenesis involving dysregulated immune responses and intestinal dysbiosis. This pathobiological interplay results in substantial impairment of patient quality of life while elevating colorectal carcinogenesis risk. Current therapeutic strategies primarily focus on inflammatory suppression and sustained remission, yet the clinical effectiveness is compromised by nonspecific biodistribution and systemic adverse events. Emerging evidence underscores the therapeutic potential of probiotics in preventing and treating IBD. Probiotics contribute to intestinal health by restoring microbial equilibrium, enhancing gut barrier function, and mitigating inflammation. Probiotics enhance immune function and stimulate the production of short-chain fatty acids (SCFAs), essential for intestinal health. However, the effectiveness of natural probiotics is often undermined by the harsh gastrointestinal environment, including poor gastric acid survival and weak mucosal adhesion, as well as physiological factors like oxidative stress from reactive oxygen species (ROS) and variable antibiotic exposure. To overcome these challenges, single-cell surface modification strategies have been developed to enhance probiotic functionality, stability, and targeted delivery. This review provides a comprehensive summary of recent advancements in probiotic surface modification technologies. It analyzes their classification, structural design, and functional attributes, systematically comparing physical, chemical, and biological strategies. This review also discusses the benefits, limitations, challenges, and future prospects of single-cell probiotic modification.