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

Table 2 Determinants of the developing paediatric gut virome

Factor	Primary impact on virome composition	Age-dependent outcome
Mode of delivery	Vaginal: Vertical seeding of maternal phages (e.g., Caudoviricetes). C-section: Initial colonization by skin-associated and environmental viruses	VD: Earlier stabilization of the bacteriome-phage axis. CS: Delayed maturation and reduced alpha-diversity up to 24 months
Infant diet	Breast milk: Direct transfer of TTV/CMV; HMOs act as “decoy receptors” for pathogens. Formula: Distinct eukaryotic signature; lacks maternal immune factors	Breastfed: Sustained “healthy” phage-host dynamics; lower risk of early-life viral gastroenteritis. Formula-fed: More rapid diversification but may lack protective “pioneer” phages
Antibiotic use	“Viral collapse”: Loss of bacterial hosts leads to secondary phage depletion; induction of prophages (lytic cycle)	Reduced richness and a “bloom” of antibiotic-resistance genes within the viral reservoir; long-term instability
Social environment	Presence of older siblings and pets acts as a vector for “socially transmitted” eukaryotic viruses	Increased eukaryotic viral richness at 1-2 years; potentially beneficial “immune training” through non-pathogenic exposure
Geography	Urban vs. Rural: Rural living is associated with higher viral diversity and distinct metabolic gene profiles (vAMGs)	Rural viromes tend to converge toward a stable “adult-like” state more resiliently than urban counterparts
Host maturity (age)	Shift from a phage-dominated (predatory) state to a eukaryotic-inclusive (commensal) state	Conversion from chaotic/volatile infancy to a stable, “adult-like” personal virome by age 2 to 5

CMV: Cytomegalovitrus; CS: Cesarean section; HMOs: Human milk oligosaccahrides; TTV: Torque teno virus; vAMGs: Viral auxiliary metabolic genes; VD: Naginal delivery.