The most pronounced colonization of the newborn infant occurs in the intestine. The mucosal epithelium of the gastrointestinal tract is the largest surface of the human body where an important cross talk between microbial antigens, epithelial cells and the immune system takes place. These interactions seem to be of major importance for intestinal and epithelial homeostasis as well as for immune maturation, as demonstrated in several different murine models. While the gut microbiota composition of a healthy adult is remarkably stable, the neonatal microbiota is very dynamic, and apparently dependent on factors such as delivery mode, hygienic standards and antibiotic usage.

In our work, we have demonstrated that the presence of lactobacilli in the very early neonatal gut seems to protect against allergy development, also in children with a high allergy-risk (two allergic parents) (1-2). Also, there are strong correlations between the early-life gut microbiota composition and immune functions during infancy, with lactobacilli connected to a more regulated immune function (3-4). We have investigated different gut microbes and their influence on the immune system in several in vitro studies, which have further supported the moderating role of lactobacilli on both epithelial and different immune cells (4-10), and further revealed how Staphylococcus aureus trigger a broad type of immune response, including both regulatory and inflammatory features. We have also been able to demonstrate that a human flora lacking lactobacilli is a strong driver of Th17-immune profile in mice, in small- and large intestines as well as in spleen (11).

In parallel, we have explored how latent herpesviruses, like Epstein Barr virus (EBV) and Cytomegalovirus (CMV), influence immune development and function in early years. They are both widely spread herpesviruses that infect immune cells and establish latency and are considered as a part of our “virobiome”. Although herpesvirus latency influences the immune system also in the asymptomatic host, the mechanisms behind this are still not very clear.

We have described that an early EBV-infection is associated with a protection against early and persistent IgE-sensitization (12) but that there is a striking delay in EBV and CMV infection in Swedish children during recent years (13). This delayed infection pattern could have consequences for immune maturation in children as both EBV and CMV latency associate with significant impact on immune parameters in children. (14-17).

We continue to investigate by what mechanisms the microbe-mediated immune maturation is induced, with a focus on epigenetic modifications of dendritic cells and how this affects T- and B-cell responses. We also aim to characterize the microbe-derived factors that cause the observed immune modulatory effects.

Further, we study how different gut microbes interact with and influence the gut epithelium in terms of integrity, permeability and function in vitro with both epithelial cell lines and primary epithelial cells. We complement this with studies on how in vivo colonization/exposure influences the gut and immune function in mice and in humans in different models and clinical studies.


  1. Sjögren YM, Jenmalm MC, Fagerås-Böttcher M, Björkstén B, Sverremark-Ekström E. Altered early infant gut flora in children developing allergy up to five years of age. Clin Exp Allergy 2009; 39: 518-526.
  2. Johansson MA, Sjögren YM, Persson JO, Nilsson C, Sverremark-Ekström E. Early Lactobacilli colonization decreases the risk for allergy at five years of age despite allergic heredity. PloS One 2011; 6(8):e23031.
  3. Sjögren YM, Tomicic S, Lundberg A, Böttcher MF, Björkstén B, Sverremark-Ekström E, Jenmalm MC. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clin Exp Allergy 2009; 39: 1842-1851.
  4. Johansson MA, Saghafian-Hedengren S, Haileselassie Y, Roos S, Troye-Blomberg M, Nilsson C, Sverremark-Ekström E. The early-life gut microbiota associates with IL-4, IL-10 and IFN- production at two years of age. PloS One 2012; 7(11): e49315.
  5. Björkander S, Johansson MA, Hell L, Nilsson C, Holmlund U, Sverremark-Ekström E. FOXP3+CD4 T cell maturity and cytokine responses to microbial stimulation alter with age and associate with early gut colonization.  J Allergy Clin Immunol; 2016; 138: 905-8.e4.
  6. Haileselassie Y, Johansson MA, Zimmer CL, Björkander S, Petursdottir DH, Dicksved J, Petersson M, Persson JO, Fernández C, Holmlund U, Sverremark-Ekström E. Lactobacilli regulate Staphylococcus aureus 161:2-induced proinflammatory T cell responses in vitro. PLoS One 2013; 8(10): e77893.
  7. Björkander S, Hell L, Johansson MA, Mata Forsberg M, Lasaviciute G, Roos S, Holmlund U, Sverremark-Ekström E. Staphylococcus aureus-derived factors induce IL-10, IFN-γ and IL-17A-producing FOXP3+CD161+ T-helper cells in a partly monocyte-dependent manner. Sci Rep; 2016; 6: 22083.
  8. Haileselassie Y, Navis M, Vu N, Qazi KR, Rethi, Sverremark-Ekström E. Postbiotic modulation of retinoic acid imprinted mucosal-like dendritic cells by probiotic Lactobacillus reuteri 17938 in vitro. Front. Immunol. 2016; Mar 17; 7: 96.
  9. Haileselassie Y, Navis M, Vu N, Qazi KR, Rethi B, Sverremark-Ekström E. Lactobacillus reuteri and Staphylococcus aureus differentially influence the generation of monocyte-derived dendritic cells and subsequent autologous T cell responses. Immun Inflamm Dis 2016; 4:315-26.
  10. Johansson MA, Björkander S, Mata Forsberg M, Qazi KR, Salvany Celades M, Bittmann, Eberl M, Sverremark-Ekström E. Probiotic lactobacilli modulate Staphylococcus aureus-induced activation of conventional and unconventional T cells and NK cells. Front Immunol 2016; 7:273.
  11. Petursdottir DH, Nordlander S, Qazi KR, Carvalho-Queiroz C, Ahmed O, Hell E, Haileselassie Y, Navis M, Kokkinou E, Lio I, Henneman J, Brodin B, Huseby D, Hughes DH, Udekwu K, Sverremark-Ekström E. Early-life human microbiota associated with childhood allergy promotes development of the Th17 axis in mice. 2017; Front Immunol 2017; 8: 1699.
  12. Saghafian-Hedengren S, Sverremark-Ekström E, Lilja G, Linde A, Nilsson C. Early life EBV-infection protects against persistent IgE-sensitization. J Allergy Clin Immunol 2010; 125: 433-438.
  13. Carvalho-Queiroz C, Johansson MA, Persson JO, Jörtsö E, Kjerstadius T, Nilsson C, Saghafian-Hedengren S, Sverremark-Ekström E. Associations between EBV and CMV seropositivity, early exposures and gut microbiota in a prospective birth cohort: a 10-year follow-up. Front Pediatr 2016; 4: 93.
  14. Saghafian-Hedengren S, Sundström S, Sohlberg E, Nilsson C, Troye-Blomberg M, Berg L, Sverremark-Ekström E. Herpes virus seropositivity in childhood associates with decreased monocyte-induced NK-cell IFN-g production. J Immunol 2009; 182: 2511-2517.
  15. Sohlberg E, Saghafian-Hedengren S, Rasul E, Giovanna Marchini, Nilsson C, Klein E, Nagy N, Sverremark-Ekström E. Cytomegalovirus-seropositive children show inhibition of in vitro EBV-induced B-cell infection that is associated with CD8+CD57+ T-cell enrichment and IFN-g. J Immunol 2013; 191: 5669-76.
  16. Saghafian-Hedengren S, Sohlberg S, Theorell J, Carvalho-Queiroz C, Nagy N, Nilsson C, Bryceson Y, Sverremark-Ekström E. Epstein-Barr virus co-infection in children boosts cytomegalovirus-related differentiation of Natural Killer cells. J Virol 2013; 87: 13446-55.
  17. Lasaviciute G, Björkander S, Carvalho-Queiroz C, Hed-Myrenberg I, Nüssbaum B, Nilsson C, Bemark M, Nilsson A, Sverremark-Ekström E*, Saghafian-Hedengren S*. EBV-, but not CMV-latency, accelerates the decay of childhood measles and rubella vaccine responses – A 10-year follow-up of a Swedish birth cohort. Front Immunol 2017; 8: 1865. * Shared senior authorship.