Post‐Microbial Therapeutics for the Next Generation of Medicine

ABSTRACT Post‐microbial therapeutics is proposed here as an integrative, function‐centered framework rather than a new therapeutic class. It asks whether a defined microbial perturbation can produce a reproducible change in a microbial function, biochemical output, and clinically relevant host phenotype. Bacteriophages provide a perturbation model because their host dependence permits strain‐selective intervention, but the framework also distinguishes between whole phages and engineered phages, lysins, depolymerases, delivery systems, and combination products. A central requirement is that a microbial module must be defined by experimentally testable functional contribution rather than by statistical co‐occurrence alone. Computationally inferred modules are therefore treated as hypotheses until supported by perturbation, reconstruction, removal/add‐back, flux, or rescue experiments. Evidence reviewed across infection, gastrointestinal, biofilm, and cardiometabolic contexts shows a recurring pattern: phage exposure can alter bacterial abundance, resistance phenotypes, community interactions, and metabolism, but the strength of evidence diminishes as claims shift from bacterial killing to ecosystem restoration and host benefit. Engineering and delivery technologies can improve targeting or exposure, yet they introduce additional constraints in genetic stability, resistance, formulation, pharmacology, and regulation. The framework is consequently best viewed as a testable translational architecture that connects intervention to function and outcome while separating established evidence from emerging hypotheses.