# A Century-Old Solution for 21st Century Challenges: Current Applications with a Focus on Biocontrol, Environmental Impacts, and Regulatory Perspectives

## TL;DR

Bacteriophages are being explored as sustainable, targeted alternatives to antibiotics and pesticides, with applications in health and agriculture, but face challenges in regulation and environmental safety.

## Contribution

This review highlights current phage applications, challenges, and innovations, advocating for tailored regulatory frameworks to support their use in sustainable practices.

## Key findings

- Phages show promise in combating antimicrobial resistance and promoting sustainable biocontrol in agriculture and health.
- Environmental safety and regulatory barriers remain key challenges for large-scale phage deployment.
- Innovations like encapsulation and protective formulations are being developed to improve phage stability and performance.

## Abstract

In the face of rising antimicrobial resistance, food insecurity, and climate change, bacteriophages are gaining renewed attention as promising biological alternatives to antibiotics across human, animal, and plant health sectors. Their high specificity, self-replicating capacity, and biodegradability make them valuable tools for combating antimicrobial or pesticide resistance and promoting sustainable biocontrol. This review discusses commonly accepted selection criteria for therapeutic phages, such as avoiding temperate types and screening for undesirable genes, while acknowledging ongoing debates and exceptions in specific clinical or ecological contexts. An overview of phage-based applications within a One Health framework is provided, spanning human medicine, veterinary practice, aquaculture, food safety and crop protection. Particular attention is given to agricultural biocontrol, where several successful plant protection strategies are highlighted, illustrating the feasibility and diversity of phage-based approaches. Despite their potential, key challenges remain regarding phage stability, formulation, and persistence under environmental conditions. Emerging innovations such as encapsulation, carrier bacteria, and protective formulations aim to enhance field performance. Furthermore, this review emphasizes the need to assess the environmental safety of phage applications, particularly their impacts on natural ecosystems, microbial communities, and ecological functions. Finally, the regulatory and policy challenges that currently limit the large-scale deployment of phages, particularly in the European Union, where they remain evaluated under conventional chemical pesticide frameworks are discussed. The development of dedicated regulatory pathways, better adapted to the specificities of phages, is argued to be essential for supporting their integration into agroecological transition strategies and next-generation antimicrobial policies.