Associations between EBV and CMV Seropositivity, Early Exposures, and Gut Microbiota in a Prospective Birth Cohort: A 10-Year Follow-up

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.

The allergic phenotype during the first 10 years of life in a prospective cohort

“…The cohort has been described in detail elsewhere. [9][10][11] Briefly, families living in Stockholm and expecting a child were invited to participate in the study. The invitation was addressed to families where the mother and the father were allergic, where only the mother but not the father had allergy or where none of the parents had allergies.…”

The influence of Epstein‐Barr virus and cytomegalovirus on childhood respiratory health: A population‐based prospective cohort study

“…Other studies also demonstrated an association of ethnicity with the prevalence of herpesviridae, although the role of other factors explaining the association such as socio‐economic or lifestyle‐related factors in these studies were less prominent . Another prospective cohort study demonstrated that maternal age was associated with time to infection for EBV and CMV, regardless of other factors such as daycare and siblings . Additionally, they demonstrated that CMV is often acquired earlier than EBV, which might be explained by the immune response after CMV infection.…”

“…32,33 Another prospective cohort study demonstrated that maternal age was associated with time to infection for EBV and CMV, regardless of other factors such as daycare and siblings. 34 Additionally, they demonstrated that CMV is often acquired earlier than EBV, which might be explained by the immune response after CMV infection.…”

Rapid Etiologic Diagnosis of Herpes Virus Infections in Children

“…vous system and organs, leading to encephalitis, hepatitis, and Hodgkin lymphoma (2,16). Among herpes viruses, EBV and CMV are more prevalent in the world and are commonly contracted during infancy (17,18). EBV and CMV reside in B lymphocytes and myeloid progenitor cells, respectively.…”

“…EBV has infected more than 90% of individuals around the world and can establish the latency after primary infection (17). Exceptionally, primary infection with EBV in older children can cause acute infectious mononucleosis instead of establishment of latency (18). Moreover, the expression of latency-related proteins and miRNA has been considered to play a role in the pathogenesis of different lymphomas (19).…”