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.

Keywords: Paediatric virome; Bacteriophages; Gut-immune axis; Dysbiosis; Necrotizing enterocolitis; Phage therapy; Microbial succession

Core Tip: The pediatric gut virome is an active biological rheostat that shapes the developmental trajectory of the infant immune system and metabolic health. Beyond serving as a reservoir for pathogens, this complex viral ecosystem-dominated by bacteriophages-governs bacterial population dynamics through lytic pressure and horizontal gene transfer. During the critical first 1000 days of life, virome disturbances triggered by antibiotics, formula feeding, or neonatal intensive care unit hospitalization can drive the pathogenesis of necrotizing enterocolitis, inflammatory bowel disease, and systemic autoimmunity. Moving forward, “illuminating” viral dark matter and leveraging precision tools such as phage therapy will be essential to transitioning toward virome-inclusive, proactive pediatric medicine.