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

Table 5 Localized gastrointestinal disorders and the pediatric virome

Condition	Primary virome alterations (effects)	Putative biological mechanism
Acute gastroenteritis	High load of Reoviridae (Rotavirus), Caliciviridae (Norovirus)	Mucosal Imprinting: Incomplete clearance leads to prolonged immune activation and “sculpting” of future immune tone
Inflammatory bowel disease	Expansion of Caudoviricetes; Contraction of overall viral diversity	Lytic pressure and HGT: Phage blooms deplete beneficial bacteria (e.g., Faecalibacterium prausnitzii) and transfer virulence genes via horizontal gene transfer
Necrotizing enterocolitis	Sudden “phage blooms” preceding symptoms; Low virome stability	The triple hit: Antibiotic-induced SOS response triggers phage lysis; viral translocation across leaky barrier activates TLR-mediated necrosis
Celiac disease	Presence of candidate viruses (Reovirus, Enterovirus)	Loss of Tolerance: Viruses act as “danger signals” that disrupt oral tolerance to gluten, triggering Th1-mediated immune priming in HLA-susceptible children
Functional gastrointestinal disorders	Specific early-life signatures; post-infectious viral “shadows”	Neuro-immune sensitization: Low-grade inflammation and viral-neural crosstalk sensitize nociceptors, leading to visceral hypersensitivity

HGT: Horizontal gene transfer; Th1: T-helper 1 lymphocyte; HLA: Human leukocyte antigen; TLR: Toll-like receptor.