噬菌体与主要动物组织互作机制及治疗潜力研究进展OA

Bacteriophage,as key regulators of animal microecosystems,dynamically modulate local microenvironments and host physiological functions through interactions with their bacterial hosts,playing a dual role in maintaining homeostasis and triggering disease progression.At present,the interaction mechanisms between bacteriophages and animal tissues remain a scientific issue that urgently requires elucidation.This review systematically expounds on the colonization characteristics and molecular interaction mechanisms of bacteriophages in major animal tissues,such as the gastrointestinal tract and central nervous system,with a particular focus on revealing the primary pathways through which bacteriophages breach the gastrointestinal epithelial barrier,blood-brain barrier,and access the central nervous system.Bacteriophages protect epithelial cells in the gastrointestinal tract through their enrichment in the mucus layer and adhesion properties,and penetrate the intestinal barrier by means of endocytosis,"Trojan horse"and passive translocation,while regulating local immune responses.Its ability to penetrate the blood-brain barrier can be achieved through linear structure,nasal administration or genetic engineering modification,providing new strategies for the treatment of the central nervous system.Bacteriophages in cerebrospinal fluid mostly enter the central nervous system through endocytosis.Their penetrating power,targeting ability and safety make them a new type of biological agent for neurological diseases.In the treatment of skin infections,bacteriophages demonstrate advantages in precise sterilization and microecological regulation.In terms of the respiratory system,although the bacteriophages administered by inhalation have a limited distribution throughout the body,they can efficiently target the infection sites in lungs and avoid immune clearance.These findings not only provide a novel theoretical framework for understanding the in vivo biodistribution of bacteriophages but also establish a scientific foundation for optimizing targeted delivery strategies in bacteriophage therapy and minimizing off-target effects.This work holds significant implications for advancing the clinical translation of phage-based therapeutics.