Summary Large cohort studies have contributed significantly to our understanding of the factors that influence the development of the bacterial component of the gut microbiome (GM) during the first years of life. However, the factors that shape the colonization by other important GM members such as the viral fraction remain more elusive. Most gut viruses are bacteriophages (phages), i.e., viruses attacking bacteria in a host specific manner, and to a lesser extent, but also widely present, eukaryotic viruses, including viruses attacking human cells. Here, we utilize the deeply phenotyped COPSAC2010 birth cohort consisting of 700 infants to investigate how social, pre-, peri- and postnatal factors may influence the gut virome composition at one year of age, where fecal virome data was available from 645 infants. Among the different exposures studied, having older siblings and living in an urban vs. rural area had the strongest impact on gut virome composition. Differential abundance analysis from a total of 16,118 viral operational taxonomic units (vOTUs) (mainly phages, but also 6.1% eukaryotic viruses) identified 2,105 vOTUs varying with environmental exposures, of which 5.9% were eukaryotic viruses and the rest was phages. Bacterial hosts for these phages were mainly predicted to be within the Bacteroidaceae, Prevotellaceae , and Ruminococcaceae families, as determined by CRISPR spacer matches. Spearman correlation coefficients indicated strong co-abundance trends of vOTUs and their targeted bacterial host, which underlined the predicted phage-host connections. Further, our findings show that some gut viruses encode important metabolic functions and how the abundance of genes encoding these functions is influenced by environmental exposures. Genes that were significantly associated with early life exposures were found in a total of 42 vOTUs. 18 of these vOTUs had their life styles predicted, with 17 of them having a temperate lifestyle. These 42 vOTUs carried genes coding for enzymes involved in alanine, aspartate and glutamate metabolism, glycolysis-gluconeogenesis, as well as fatty acid biosynthesis. The latter implies that these phages could be involved in the utilization and degradation of major dietary components and affect infant health by influencing the metabolic capacity of their bacterial host. Given the importance of the GM in early life for maturation of the immune system and maintenance of metabolic health, these findings provide a valuable source of information for understanding early life factors that predispose for autoimmune and metabolic disorders.

The influence of early life exposures on the infant gut virome