Abstract
Early-life infections with persistent Epstein–Barr virus (EBV) and cytomegalovirus (CMV) are delayed in affluent countries, probably due to alterations in early environmental exposures, such as maternal age, siblings, and day-care attendance. We have previously reported that the timing of EBV and CMV contraction is related both to allergic sensitization and changes in functional competence of immune cells, while the presence/absence of lactobacilli [Lactobacillus (L.) casei, L. paracasei, and L. rhamnosus] or Staphylococcus (S.) aureus in feces is related to the risk for allergy. Here, we used the same prospective longitudinal birth cohort of children to investigate early-life environmental exposures and their influence on EBV and CMV contraction over time. Since gut microbes also belong to this category of early exposures, we investigated their association with herpesvirus contraction. Our results show that these two viruses are acquired with different kinetics and that EBV and CMV seroprevalence at 10 years of age was 47 and 57%, respectively. We also observed that a delayed EBV or CMV infection was associated with older maternal age [time ratio (TR) 1.14, 95% confidence interval (CI) 1.07–1.21, Padj < 0.001 and TR 1.09, CI 1.03–1.16, Padj = 0.008, respectively]. Further, we present the novel finding that S. aureus colonization reduced the time to CMV acquisition (TR 0.21, CI 0.06–0.78, Padj = 0.02). Together, these findings suggest that there is a relationship between timing of herpesvirus acquisition and early-life immune modulating exposures, which interestingly also includes the early infant gut microbiota.
Highlights
Epstein–Barr virus (EBV) and cytomegalovirus (CMV) are herpesviruses commonly contracted during infancy, and they are prevalent in the human population worldwide
As the order and timing of colonization with these microbial agents has been suggested to affect functional capacity of the infant immune system [15,16,17,18,19,20,21], we investigated the seropositivity for EBV and CMV at four time points up to 10 years of age in the same children and assessed the possible association between environmental exposures, including gut microbiota colonization following birth and the acquisition of herpesviruses over a 10-year period
We investigated the associations between EBV and CMV and the presence of two different types of bacteria commonly present in the neonatal gut but with opposite effects on immune function – a group of lactobacilli (L. casei, L. paracasei, and L. rhamnosus) and S. aureus [25, 27]
Summary
Epstein–Barr virus (EBV) and cytomegalovirus (CMV) are herpesviruses commonly contracted during infancy, and they are prevalent in the human population worldwide. As the order and timing of colonization with these microbial agents has been suggested to affect functional capacity of the infant immune system [15,16,17,18,19,20,21], we investigated the seropositivity for EBV and CMV at four time points up to 10 years of age in the same children and assessed the possible association between environmental exposures, including gut microbiota colonization following birth and the acquisition of herpesviruses over a 10-year period
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