Unveiling the viral dimension: The paediatric gut virome as a key modulator of gastrointestinal metabolic, and neurodevelopmental health.

Abstract

Paediatric gut microbiome research has long been bacteriocentric, overlooking the extensive viral component known as the gut virome. Composed of bacteriophages, eukaryotic viruses, and endogenous viral elements, the paediatric gut virome is the most abundant and genetically diverse biological entity in the intestine. Emerging evidence indicates that the virome is a key regulator of microbial ecology, immune maturation, and systemic physiological programming during early life. This narrative review synthesizes current knowledge on the establishment, development, and functional roles of the paediatric gut virome, with emphasis on its interactions with the bacterial microbiome and host immune system. We highlight how early-life viral exposures influence mucosal immune imprinting, epithelial barrier integrity, and immune tolerance, particularly during the first 1000 days of life. Virome dysbiosis is increasingly associated with paediatric gastrointestinal disorders, including inflammatory bowel disease, necrotizing enterocolitis, celiac disease, and functional gastrointestinal disorders. Beyond the gut, the virome also contributes to metabolic regulation, type 1 diabetes risk, and gut-brain axis signaling, influencing neurodevelopment. Mechanistic pathways involving phage-mediated bacterial modulation, innate immune sensing, cytokine signaling, and metabolic intermediates are discussed, positioning the paediatric gut virome as a central regulator of gastrointestinal and systemic homeostasis.