Decolonizing the gut from multidrug-resistant bacteria: Current strategies and future perspectives

Table 4 Challenges and potential solutions in phage therapy

Challenge	Description	Potential solutions
Narrow host range	Phages are highly specific, targeting only a limited range of bacterial strains	Develop phage cocktails targeting multiple strains
Bacterial resistance development	Bacteria may evolve resistance to phages, just like with antibiotics	Using phage combinations or cocktails; engineer phages to overcome resistance
Immunogenicity of phages	The human immune system may neutralize phages, limiting their effectiveness	Use encapsulation techniques (e.g., liposomes) to shield phages; select less immunogenic phages
Phage clearance by organs	The liver and spleen may rapidly clear phages from the bloodstream	Modifications in phages to evade immune detection; optimize dosing regimens to maintain therapeutic levels
Horizontal gene transfer risk	Temperate phages can transfer harmful genes (e.g., toxin or resistance genes) between bacteria	Prefer strictly lytic phages over temperate ones; genetically screen and engineer phages for safety
Storage and stability	Phages can lose viability due to improper storage conditions	Optimize formulations and storage conditions (e.g., lyophilization, buffer systems) for stability
Lack of standardized regulations	Absence of global guidelines makes approval and clinical use challenging	Developing common regulatory frameworks; global collaborations on phage therapy policies
Limited clinical trials	Few large-scale, randomized controlled trials exist to validate efficacy and safety	Encourage funding and support for rigorous clinical studies to build evidence for medical approval