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Lifelines NEXT cohort study,

Publications and source records attributed to Lifelines NEXT cohort study,.

3 recordsLinked to original sources

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

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.

microbiology↗

Pregnancy and Early-Life Gut Virome in the Lifelines NEXT cohort:Origin, Persistence, Influencing Factors and Health Implications

The human gut virome is a key modulator of gut microbial ecology and function, yet its role in early gut ecosystem development remains poorly understood. Here, we profiled the DNA virome from 4,523 fecal and 91 breastmilk metagenomes from 714 mother-infant pairs in the Dutch birth cohort Lifelines NEXT. This analysis generated a catalog of 31,205 unique vOTUs, with 31,019 detected in fecal and 248 in breastmilk samples, including 16,540 not previously reported in other databases. We find that the maternal virome is largely stable, in contrast to the infant viromes rapid diversification over time. We also identify delivery and feeding modes as major drivers of infant virome developmental trajectories, with additional influences of maternal parity, infections during pregnancy, socioeconomic factors, gestational age and infant birth weight. Notably, increased viral diversity was associated with the infant developing a food allergy. Strain-level virome profiling confirmed the maternal gut as the primary source of viruses for the infant gut, with increased sharing rates in vaginally delivered infants and with breastmilk as a secondary reservoir. We demonstrate that temperate phages frequently co-transmit with their bacterial hosts and identify multiple protein families associated with anti-defense functions enriched among maternally shared viruses. Finally, we show that DNA adenine N6-methyltransferase hin1523, together with widely active diversity-generating retroelements, promote long-term viral persistence in the infant and maternal gut. Together, these findings establish the origin, dynamics and modulating factors of the infant gut virome, along with the genetic strategies supporting its persistence in the gut ecosystem.

microbiology↗

Prophages of infant-derived Bifidobacterium longum subspecies employ antagonistic and synergistic strategies to persist in their host

Early colonisation by bifidobacteria is crucial for infant health, with Bifidobacterium longum subspecies (BL.) dominating the early gut microbiome. However, the interactions between these bacteria and their viruses remain poorly characterised. Here, we applied genomics-based approaches to examine BL. prophage composition and dynamics in infants, as well as their antagonistic and mutualistic evolutionary strategies. Across 213 metagenome-assembled genomes recovered from 139 infant faecal samples in the Dutch Lifelines NEXT cohort, 286 previously undescribed prophages were identified and analysed. Comparative genomics revealed extensive viral diversity, evidence of historical recombination, and widespread counter-defence, with [~]80% of prophages encoding anti-CRISPR or CRISPR-evasion proteins. Approximately half of prophages encoded metabolism altering genes. Notably, prophages and host CRISPR spacer arrays were highly stable across longitudinal samples, indicating stable phage-host associations during early life. Together, these findings show that BL. prophages employ antagonistic and synergistic strategies to maintain infectivity and long-term persistence in the infant gut.

microbiology↗