Comprehensive profiling of infant gut virome assembly reveals associations with eczema and wheeze

Abstract

Infancy is a critical developmental window during which the gut ecosystem assembles and helps train the immune system, thereby setting trajectories for lifelong health. Bacteria and viruses are equally numerous in this early ecosystem, yet the gut viromes composition, dynamics, and health relevance remain poorly understood. Here, we show that the infant gut virome is diverse, dynamic, and linked to health outcomes. We performed comprehensive virome profiling of 1,110 longitudinal fecal samples from 314 mother-infant pairs from the Dutch birth cohort Lifelines NEXT using both virus-like particle enrichment (VLP) and total metagenomic sequencing (MGS). We find only 18.9% compositional overlap between the VLP- and MGS-metaviromes, with VLP recovering the active virome and most novel species and MGS predominantly capturing temperate phages. By combining both methods, we identified 8,348 novel virus species spanning diverse hosts, from bacteria to humans, and all major viral genome types (dsDNA, ssDNA, and RNA). We find that bacteriophages frequently encode metabolic functions, including genes related to B vitamin metabolism. We further observe that the development of the infant gut virome is shaped by both host factors, including delivery mode and feeding practices, and continuous switching of temperate phage lifecycles. Notably, the relative abundance of induced temperate phages is also associated with eczema development within the first year of life. Together, these findings establish the infant gut virome as a dynamic and clinically relevant component of early-life microbial development and highlight how comprehensive dual-method profiling is a necessary framework for future virome research.