Correlation between early-life regulation of the immune system by microbiota and allergy development

Abstract

Early postnatal life is a key time for development of the immune system and colonization of the host by microbiota. Recent studies have shown that specific limbs of the immune system can be regulated by microbiota in a time-restricted period during early life. Studies in mouse models have shown that perturbations of the microbiota during early life can cause immune effects that can persist into adulthood and create increased host susceptibility to certain diseases. Here we discuss the role of early-life regulation of the immune system by the microbiota and how it can be related to allergy development.

Keywords: Allergy; early-life; microbiota; neonate; window of opportunity.

Figure 1

Evolution of microbiota from birth to adult life. Microbial diversity increases from birth to 3 years of life and stabilizes. Genetics, the type of birth, diet and environmental factors are associated with differences in intestinal microbial composition.

Figure 2

Role of early life microbiota in the regulation of iNKT cells and development of allergic disease in human and mouse. Caesarean section and antibiotic treatment are associated with modifications of the microbiota in early life and to EoE development in later human life. Whether these microbial modifications are directly related to these diseases in humans remains to be established. EoE development is an allergic disease that depends on iNKT cell activation. iNKT cell numbers as well as CXCL16 and CD1d expression are increased in EoE patients less than 5 years of age. These increases are normalized by an elimination diet. An absence of microbiota in GF mice during early life leads to an accumulation of lung iNKT cells, increased CXCL16 expression and increased susceptibility to asthma in later life. Conventionalization with microbiota during a specific early life time frame, but not thereafter, can normalize the number of iNKT cells in the lung and susceptibility to colitis and asthma.

Figure 3

Role of early life microbiota in the regulation of Treg cells and development of allergic diseases in human and mouse. High microbial exposure during early life is associated with asthma protection as well as increased Treg cells function in the cord blood of the fetus. In mice, HDM exposure during early life but not thereafter protects from asthma due to the emergence of an induced (helios negative) Treg cells. Treg cells have the capacity to accumulate in the skin of mice in response to colonization with a skin commensal bacterial strain specifically during early life and are required to establish tolerance to commensal derived antigens in the adult. HDM, house dust mite.