First-year dynamics of the plasma virome and cytokine profile in infants born to mothers with syphilis

BACKGROUND: The early-life development of the human plasma virome and its immunological implications remain poorly understood. We aimed to explore the dynamic interplay between viral colonization and immune maturation in infancy. METHODS: We conducted a retrospective longitudinal study of the plasma virome and cytokine profile in a cohort of 77 pregnant women with syphilis and their 89 infants. Plasma samples were collected from mothers at delivery and infants at multiple time points (the first day, and at 3, 6, 9 and 12 months of age). Virome composition was characterized via metagenomic sequencing, and 27 cytokine concentrations were quantified using multiplex immunoassays. The impacts of delivery mode, feeding patterns, and anti-syphilitic treatment on the development of plasma virome were investigated. Mother-infant vertical transmission of anelloviruses was validated by phylogenetic analysis with MEGA (v1.2.9). RESULTS: The infant plasma virome was composed mainly of host-associated viruses (42.5%, primarily Anelloviridae) and phages (45.5%). Phages dominated the neonatal plasma virome at birth, but declined accompanied with a rapid expansion of host-derived viruses (96.1% at 12 months) during the first year of life. Human-host viruses were rarely detected in neonates at birth, with their richness and abundance increaing notably after 3 months of life. Shared human-host viruses with mothers were observed at the neonates at birth and increased in virus number and abundance in the first year of life. Mother-to-infant perinatal vertical transmission of anelloviruses were validated by transmission cluster analysis using all identified anelloviruses ORF1 lineages at delivery. Delivery mode, environment exposure, and feeding pattern had no significant effect on virome diversity. Compared with their mothers, the neonates exhibited higher plasma levels of eotaxin, FGF basic, GM-CSF, MCP-1, MIP-1α, MIP-1β, VEGF, IFN-γ, IL-5, IL-9, IL-10, IL-17 A, and TNF-α at birth. During months 3 to 6, infant IL-6 levels declined, while IL-13 and IP-10 levels gradually increased. From month 3, Anelloviridae abundance positively correlated with IL-6, IL-9, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α in infants, and with MCP-1 and MIP-1α in maternal plasma. CONCLUSION: Our findings reveal dynamic developmental trajectories of the virome and immune system and suggest that early virome exposures may influence immune development, providing a basis for future maternal-child health interventions.