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.

Epstein Barr virus (EBV) and Cytomegalovirus (CMV) are both widely spread herpesviruses that infect immune cells and establish latency (in B cells and in cells of the monocytic lineage respectively) in the host after primary infection and they are considered as a part of our “virobiome”. The time-point for infection is associated with socio-economic conditions, and sero-conversion occurs comparably late in westernized countries. Although herpesvirus latency influences the immune system also in the asymptomatic host, the mechanisms behind this are still not very clear. As herpesviruses and man have co-evolved for a long time, several of these virus-induced effects on our immune system could be beneficial are at least confer an immunological imprint that we consider as “normal”.

Although there is considerable evidence for a role of early-life microbial exposures for immune (and allergy) development during childhood, other early exposures may also influence the developing immune system. In particular, exposure to an altered intrauterine environment due to maternal immune-mediated disease could be of importance.