Interactions in the gut: microbiota, epithelium and immune cells

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 a lower prevalence of lactobacilli and bifidobacteria in children who develop allergy during their first five years of life, indicating a reduced diversity of the gut microbiota. When studying children with allergic heredity we further observed 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). Being colonized with lactobacilli early in life is associated with dampened inflammatory immune responses. Our in vitro studies confirmed that lactobacilli down-regulate inflammatory-associated responses characterized by IL-17, IFN-γ and TNF production induced by other bacteria like Staphylococcus aureus – a typical skin bacteria which is nowadays common in the neonatal intestine.

We continue to investigate 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. Further, we study how these bacteria-epithelia interactions influence immune function in vitro as well as how the microbiota composition relates to immune function during childhood. In particular, different conventional as well as unconventional types of T- cells, antigen-presenting cells and B cells are investigated in detail both in terms of phenotypical and functional characteristics. 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

Johansson, M.A., Saghafian-Hedengren, S., Haileselassie, Y., Roos, S., Troye-Blomberg, M., Nilsson, C., & Sverremark-Ekström, E. (2012). The early-life gut microbiota associates with IL-4, IL-10 and IFN-γ production at two years of age. PloS One. 7(11):e49315

Johansson. M.A., Sjögren, Y.M., Persson, J.O., Nilsson, C., & Sverremark-Ekström, E. (2011). Early colonization with a group of Lactobacilli decreases the risk for allergy at five years of age despite allergic heredity. PloS One. 6(8):e23031.

Sjögren, Y.M., Jenmalm, M.C., Fagerås-Böttcher, M., Björkstén, B., & Sverremark-Ekström, E. (2009). Altered early infant gut flora in children developing allergy up to five years of age. Clin Exp Allergy. 39:518-26

Sjögren, Y.M., Tomicic, S., Lundberg, A., Böttcher, M.F., Björkstén, B., Sverremark-Ekström, E., & Jenmalm, M.C. (2009). Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clin Exp Allergy. 39:1842-51