The most pronounced colonization of the newborn infant occurs in the intestine and the establishment of the gut microbiota starts immediately during and after birth. 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 highly dependent on factors such as delivery mode, hygienic standards and antibiotic usage.

In our work, we have demonstrated that children, who develop allergy during their first 5 years of life, have a reduced biodiversity and altered gut flora composition in very early fecal samples (Sjögren et al 2009(a), Johansson et al 2011). In particular we have demonstrated that those children who were early colonized with lactobacilli did not develop allergy (in spite of two allergic parents), suggesting that early lactobacilli colonization may protect against allergy development. In addition we have demonstrated that the early life gut microbiota composition influences both mucosal and systemic immune responses during childhood in a species-specific manner (Sjögren et al 2009(b), Johansson et al 2012). Our in vitro studies confirmed that lactobacilli down-regulate inflammatory-associated responses induced by other bacteria like Staphylococcus (S.) aureus –a typical skin bacterium -which is nowadays common in the neonatal intestine (Haileselassie et al 2013). In our most recent work, we have shown that S. aureus has significant impact on the regulatory cell compartment in both adults and children, and that early colonization with S. aureus correlates with regulatory T cell characteristics (Björkander et al). In addition we have shown a significant impact of lactobacilli on the maturation of both conventional and mucosal dendritic cells, with consequences for subsequent T cell responses (Haileselassie et al). We have also continued to study the mechanisms of the regulatory effects of lactobacilli in vitro (Björkander, Mata-Forsberg, Johansson et al) and performed proof-of concept studies in vivo in murine models (Petursdottir, Nordlander, Qazi, Carvalho-Qeiroz et al).

We continue to investigate how the bacteria-mediated immune maturation is induced and what factors that are mediating the effects in different cell types. 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 (colonization of germ-free mice) and in humans (double-blind placebo controlled probiotic study of extremely pre-term neonates).

 

References

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.

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-g production at two years of age. PloS One 2012; 7(11): e49315.

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. Epub 2011 Aug 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(a); 39: 518-526.

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(b); 39: 1842-1851.