Gut virome dynamics: from commensal to critical player in health and disease.

The gut virome is a complex ecosystem characterized by the interplay of diverse viral entities, predominantly bacteriophages and eukaryotic viruses. The gut virome has a critical role in human health by shaping microbial community profiles, modulating host immunity and influencing metabolic processes. Different viral metagenomics approaches have revealed the remarkable diversity of the gut virome, showing individual-specific patterns that evolve over time and adapt dynamically to environmental factors. Perturbations in this community are increasingly associated with chronic immune and inflammatory conditions, metabolic disorders and neurological conditions, highlighting its potential as a diagnostic biomarker and therapeutic target. The early-life gut virome is particularly influential in establishing lifelong health trajectories through its interactions with diet, immune pathways and others, thereby contributing to inflammatory and metabolic regulation. This Review synthesizes current knowledge of gut virome composition, dynamics and functional relevance, critically evaluating evidence distinguishing causal from correlative roles in disease pathogenesis. The interactions of the virome with other microbiome components and host immunity are examined, and emerging translational applications, including phage therapy and biomarker development, are discussed. Integrating these insights while acknowledging methodological challenges provides a comprehensive framework for understanding the complex roles of the gut virome in health and disease.