Rehabilitation of a misbehaving microbiome: phages for the remodeling of bacterial composition and function

The human gut microbiota is considered an adjunct metabolic organ owing to its health impact. Recent studies have shown correlations between gut phage composition and host health. Whereas phage therapy has popularized virulent phages as antimicrobials, both virulent and temperate phages have a natural ecological relationship with their cognate bacteria. Characterization of this evolutionary coadaptation has led to other emergent therapeutic phage applications that do not necessarily rely on bacterial eradication or target pathogens. Here, we present an overview of the tripartite relationship between phages, bacteria, and the mammalian host, and highlight applications of the wildtype and genetically engineered phage for gut microbiome remodeling. In light of new and varied strategies, we propose to categorize phage applications aiming to modulate bacterial composition or function as “phage rehabilitation.” By delineating phage rehab from phage therapy, we believe it will enable greater nuance and understanding of these new phage-based technologies.