Childhood health; the role of the microbiome in the path to atopy

Background

Over the past decades the occurrence of atopic disorders has increased, however the trends in this increase vary globally. With on the one hand an increase in incidence in low- to middle- income countries, while on the other hand the incidence has reached a plateau in some developed countries. Even so, hundreds of millions of children are still affected by allergic diseases. For example, asthma remains the most common chronic childhood disease with an estimated half million deaths per year that can be attributed to undertreated, underdiagnosed or treatment resistant asthma.

The term atopy is used to indicate the susceptibility of developing allergic diseases, including atopic dermatitis, allergic rhinitis, and asthma. The susceptibility for atopy is mediated through the disposition to develop immunoglobulin E (IgE) directed against common (environmental) allergens, through a type-2 inflammatory response. An aberrant type-2 inflammatory response results in the production of allergen specific IgE by plasma cells. Of the atopic disorders, atopic dermatitis tends to manifest before allergic rhinitis (and food allergies) and asthma occur. This sequential occurrence of atopic disorders is also referred to as the atopic march. However, atopic disorders are often studied in isolation, while they can share underlying biological mechanisms.

One of the mechanisms that has been implicated in an aberrant type-2 inflammatory immune response constitutes the establishment of improper immune-microbe interactions. At time of birth the newborn undergoes a drastic change in environment, to which it must rapidly adapt. In healthy situations, birth is generally considered the first moment during which a newborn encounters the first microbes. These first microbes an infant interacts with originate from the mother and form the basis for the development of the infant microbiome. Since the newborns’ immune system has not yet fully developed at time of birth, the interactions with early life microbes play an important role in the education and development of the immune system. Consequently, early life events that disturb the infant’s microbiome (e.g. antibiotic use, birth mode, breastfeeding), may impact immune development and result in aberrant immune-microbe interactions. The establishment of aberrant immune-microbe relationships can therefore have serious consequences for future health. Consequently, the aim of this thesis is to understand early life events and their role in the establishment of the infant’s microbiome and in the trajectory to childhood health outcomes with a particular focus on atopy.

Overall Research goals:

1. Identify early life events related to health outcomes later in life, including:
• Risk factors for atopic symptoms over the first 5 years of life
• Risk factors related to growth outcomes in the first 5 years of life
2. Understand the relation between early life respiratory microbiome and childhood asthma
3. Understand if the microbiome is a potential mediator between epidemiological risk factors and health outcomes 1
4. Identify the window of opportunity to modify above identified factors.1
5. Understand the relation between microbiota profiles and asthma exacerbation

Contact 
Fien van Beveren