title: 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, P adj < 0.001 and TR 1.09, CI 1.03-1.16, P adj = 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, P adj = 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.
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University , Stockholm , Sweden.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carvalho-Queiroz
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University , Stockholm , Sweden.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Johansson
authors.affiliation: Department of Mathematics, Stockholm University , Stockholm , Sweden.
authors.forename: Jan-Olov
authors.initials: JO
authors.lastname: Persson
authors.affiliation: Department of Clinical Science and Education, Karolinska Institute, Stockholm, Sweden; Sachs' Children's and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden.
authors.forename: Evelina
authors.initials: E
authors.lastname: Jörtsö
authors.affiliation: Department of Clinical Virology and Microbiology, Karolinska University Laboratory, Solna, Sweden; Department of Clinical Microbiology, Central Hospital, Karlstad, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Kjerstadius
authors.affiliation: Department of Clinical Science and Education, Karolinska Institute, Stockholm, Sweden; Sachs' Children's and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Nilsson
authors.affiliation: Department of Women's and Children's Health, Paediatric Oncology Unit, Astrid Lindgren Children's Hospital, Karolinska Institute , Sweden.
authors.forename: Shanie
authors.initials: S
authors.lastname: Saghafian-Hedengren
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University , Stockholm , Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Sverremark-Ekström
keywords: CMV; EBV; Lactobacillus; S. aureus; gut microbiota; healthy children; risk factors; seroprevalence