The phageome in critical illness: bacteriophage–bacteria interactions, resistome dynamics, and pathogen domination in the intensive care unit

Critical illness disrupts microbial communities through antimicrobial exposure, altered nutrient supply, tissue injury, and loss of anatomical barriers. Bacterial profiling has linked these disturbances to pathogen domination and infection, but bacteria participate in ecosystems that also contain bacteriophages, eukaryotic viruses, and mobile genetic elements. This narrative review examines how the phageome may influence microbial ecological transitions during critical illness, including changes in colonization resistance, pathogen domination, and the potential progression to invasive infection. We integrate recent human observations with experimental evidence on phage predation, lysogeny, bacterial defense, spatial organization, and resistance-gene mobility. Longitudinal respiratory viromics and circulating phage DNA studies provide direct clinical entry points, whereas much of the mechanistic evidence originates from healthy volunteers, inflammatory disease cohorts, cultured communities, and animal models. These evidence levels support an ecological framework but do not establish a universal phage-mediated pathway to ICU infection. Phages can suppress susceptible pathogens, remove protective commensals, select resistant bacterial phenotypes, or support lysogen fitness. Their contribution to antimicrobial resistance extends beyond resistance genes encoded within phage genomes to transduction, phage–plasmid exchange, and indirect effects on conjugation and community composition. Interpretation requires separating viral detection from productive infection, bacterial DNA packaging from successful transfer, and relative abundance from absolute expansion. We propose a compartment-aware longitudinal research framework combining viral-particle and bulk metagenomics, bacterial strain resolution, functional validation, and prospectively adjudicated clinical events. The immediate clinical opportunity is to determine whether phage measurements add actionable information to bacterial surveillance; therapeutic manipulation remains a downstream application requiring ecological and clinical validation.