Gut virome characteristics associated with early onset of anemia and neurodevelopmental delay in preterm infants

Early-onset anemia (EOA) and neurodevelopmental delay (NDD) are highly prevalent in preterm infants, causing substantial long-term health impacts. This study aimed to identify distinctive gut virome characteristics and their associations with EOA and NDD. We hypothesized that gut microbial colonization types and bacteriophage profiles may be risk factors for NDD in preterm infants with EOA. Fecal samples from 107 healthy preterm infants within the first week of life underwent virome and 16S rRNA sequencing. Consensus clustering of viral species signatures divided infants into four groups. The high EOA risk group showed significantly higher virome alpha diversity. Enriched Circoviridae sp. and uncultured Caudoviridae phage, along with reduced CRESS virus sp., were linked to elevated NDD risk. Geobacillus virus Tp84—the only bacteriophage exhibiting both temperate and virulent lifestyles—was associated with high EOA risk but low NDD risk. These findings highlight the role of gut virome in EOA and NDD pathogenesis, suggesting potential for targeted bacteriophage-based interventions to mitigate EOA-related NDD in preterm infants.