Engineering bacteriophages for gut health: precision antimicrobials and beyond
Mengmeng Xu, Shuling Chen, Hailong Pei, Lin Hu, Yongsheng Zhang
Abstract
Engineered bacteriophages are emerging as a promising class of precision antimicrobials at a time when gastrointestinal diseases are increasingly linked to microbial dysbiosis, antibiotic resistance, and disruptions in host-microbe interactions. Conventional antibiotics often provide limited benefit in these settings because they lack selectivity and fail to restore microbial ecology. Advances in synthetic biology and nanotechnology have made it possible to redesign phages with enhanced specificity, expanded functionality, and improved stability, positioning them as versatile tools for microbiota-centered therapies. This review summarizes the major engineering approaches, and examines their applications in inflammatory bowel disease (IBD), colorectal cancer (CRC), and infectious enteritis. Key mechanistic insights into pathogen targeting, immune modulation, and barrier protection are highlighted. Remaining challenges, such as ensuring long-term stability, avoiding resistance development, and enabling scalable manufacturing, are discussed together with emerging interdisciplinary strategies that may advance the clinical translation of personalized phage therapies.