The Evaluation of Bacteriophage Therapy in Aquaculture: A Systematic Review and Meta-Analysis

The progressively intensifying misuse of antibiotics has caused a serious threat to the sustainable and sound development of aquaculture industry through the transfer of antibiotic resistance genes and the formation of multidrug-resistant bacteria, further leading to significant food and public health risks. Therefore, there is an urgent need for a new sustainable alternative treatment for antibiotics. Bacteriophages with high host specificity, have gradually attracted attention as relatively safe biological substitutes for antibiotics. However, there is a lack of systematic evaluation on the therapeutic effects and usage methods of bacteriophage treatment. In this meta-analysis, we investigated the therapeutic effect of bacteriophage therapy on aquatic animals and potential influencing factors, and analyzed the possibility of bacteriophages replacing antibiotics as a new biological control agent. A total of 3547 studies from five databases including PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure, and Wanfang published within the past ten years were retrieved. After applying exclusion and inclusion criteria, a total of 32 studies with 67 datasets were included. Using a random-effects model, the results were pooled, and statistical heterogeneity between the data was assessed using Cochrane's Q test and I2 statistic. The results of the meta-regression and subgroup analysis showed that the therapeutic effect of bacteriophages was significantly influenced by multiplicity of infection (MOI) (p = 0.005, R2 = 11.97%) and treatment duration (p = 0.019, R2 = 8.00%). Moreover, there was no significant difference in the therapeutic effect between bacteriophages and antibiotics. In conclusion, our findings suggest that bacteriophages have great potential as alternatives to antibiotics in aquaculture. These results provide evidence-based guidance for the practical application of bacteriophage preparations in the aquaculture industry.