Synergistic effects of commensals and phage predation in combating pathogen infections: a shrimp model

Abstract

Colonization resistance is a fundamental mechanism by which microbiomes suppress pathogen invasion, yet the factors governing its efficacy remain unclear. By constructing a defined microbial consortium and employing in vivo models, we provide evidence supporting that phage-mediated pathogen suppression interacts with competitive dynamics within microbial communities to enhance colonization resistance. While individual species conferred limited protection, combining key taxa with phage treatment extensively improved pathogen exclusion. Phage-induced pathogen killing amplified nutrient competition among commensals, however, the timing intervention emerged as a crucial determinant of efficacy. Guided by these ecological principles, we formulated a minimal, synergistic consortium that robustly enhanced colonization resistance in vivo. These findings advance our understanding of microbiome-driven pathogen resistance and provide a strategic framework for designing protective microbial consortia with potential applications in human and animal health.