Phage Therapy for Intestinal Infections: Efficacy, Challenges, and Future Directions in Translational Research

晶晶 李¹Zimo Ge¹Junhao Fan¹Dongdao Ma¹Huiru Cao¹Jiawen Shen¹Yange Wang¹Zhongyi Yan¹Salwa E. Gomaa^1,2Xianghui Li^1*Xin-Ying Ji^3,4,5*Xiaotao Dong^1*

• ¹Henan University, Kaifeng, China
• ²Zagazig University Faculty of Pharmacy, Zagazig, Egypt
• ³Henan International Joint Laboratory for Nuclear Protein Regulation, the First Affiliated Hospital, Henan University College of Medicine, Ximen St, Kaifeng, Henan 475004, China, Kaifeng, China
• ⁴Department of Nuclear Medicine, Henan International Joint Laboratory for Nuclear Protein Regulation, the First Affiliated Hospital, Henan University College of Medicine, Ximen St, Kaifeng,, Kaifeng, China
• ⁵Henan Provincial Research Center of Engineering Technology for Nuclear Protein Medical Detection, Zhengzhou Health College, Zhengzhou, Henan 45000, China, zhengzhou, China

Phage therapy has emerged as a promising alternative to conventional antibiotics for combating intestinal bacterial infections, especially in the era of rising antimicrobial resistance. Despite its therapeutic potential, the clinical translation of phage therapy remains hindered by limited large-scale trial data and incomplete mechanistic understanding. This review systematically evaluates the efficacy of phage therapy in animal models of intestinal diseases, encompassing bacterial infection-induced diarrhea (e.g., cholera, typhoid fever), bacterial enteritis, and sepsis. By synthesizing evidence from bacterial colonization assays, histopathological analyses, and disease severity assessments, we highlight features such as phage-mediated pathogen clearance, changes in inflammatory factors, and intestinal pathology. Furthermore, challenges including phage selection difficulties, host specificity issues, and safety considerations are discussed, along with future research directions aimed at bridging the gap between experimental models and clinical applications.