Infant gut bacteriophage strain persistence during the first three years of life

Bacteriophages are key components of gut microbiomes, yet the phage colonization process in the infant gut remains uncertain. Here, we established a large phage sequence database and used strain-resolved analyses to investigate phage succession in infants throughout the first three years of life. Analysis of 819 fecal metagenomes collected from 28 full-term and 24 preterm infants and their mothers revealed that early-life phageome richness increased over time and reached adult-like complexity by age three. Approximately 9% of early phage colonizers, mostly maternally transmitted and infecting Bacteroides , persisted for three years and were more prevalent in full-term than in preterm infants. Although rare, phages with stop codon reassignment were more likely to persist than non-recoded phages and generally displayed an increase in in-frame re-assigned stop codons over three years. Overall, maternal seeding, stop codon reassignment, host CRISPR-Cas locus prevalence, and diverse phage populations contribute to stable viral colonization.