Reprogramming the therapeutic fate of living biotherapeutic products for intestinal diseases via biomaterials.

Abstract

Live biotherapeutic products (LBP) hold great promise for the treatment of intestinal diseases such as inflammatory bowel disease and colorectal cancer, owing to their unique abilities to modulate the gut microbiota, regulate host immunity, and influence drug metabolism. However, the use of natural strains remains constrained by several challenges, including poor survival, limited colonization efficiency, immune clearance and non-specific targeting. Rational engineering of bacteria can overcome these limitations, while biomaterials, owing to their safety and versatile functionalities, provide powerful tools for bacterial modification. Recent studies have focused on developing biomaterial-modified bacteria (BMB) using lipid-based coatings, hydrogels, organic-inorganic hybrid materials, antibody or functional protein and cell membrane. This review systematically summarizes strategies for modifying bacterial surfaces with these biomaterials, elucidates the underlying mechanisms by which they enhance bacterial performance, and highlights recent advances in this field, offering insights that may inspire the design of the next generation of BMB based on high-throughput platforms, synthetic biology, and artificial intelligence (AI).