Encapsulation and delivery of phage as a novel method for gut flora manipulation in situ: A review

Intestinal flora regulation is an effective method to intervene and treat diseases associated with microbiome imbalance. In addition to conventional probiotic supplement, phage delivery has recently exhibited great prospect in modifying gut flora composition and regulating certain gene expression of gut bacteria. However, the protein structure of phage is vulnerable to external factors during storage and delivery, which leads to the loss of infection ability and flora regulation function. Encapsulation strategy provides an effective solution for improving phage stability and precisely controlling delivery dosage. Different functional materials including enzyme-responsive and pH-responsive polymers have been used to construct encapsulation carriers to protect phages from harsh conditions and release them in the colon. Meanwhile, diverse carriers showed different characteristics in structure and function, which influenced their protective effect and delivery efficiency. This review systematically summarizes recent research progress on the phage encapsulation and delivery, with an emphasis on function properties of carrier systems in the protection effect and colon-targeted delivery. The present review may provide a theoretical reference for the encapsulation and delivery of phage as microbiota modulator, so as to expedite the development of functional material and delivery carrier, as well as the advances in practical application of intestinal flora regulation.