Subproject 7 - Microbiome: Priming of tolerance and allergy

The microbiome can shortly be defined as a community of microorganisms (such as bacteria, fungi, and viruses) that inhabit a particular environment and especially the collection of microorganisms living in or on the human body. Although the human microbiome is increasingly recognized as a regulator of immune responses, it is unknown which changes in microbial community structure play a role in tolerance development.

The knowledge about such changes can be used

• to understand which microbes are present under which conditions in the course of allergic diseases
• to design novel probiotics for the induction of tolerance, i.e. remission of allergic diseases

Primary goal of this project is to understand the role of the microbiome in the context of progression or remission of allergic diseases with a focus on asthma and food allergy. To achieve this, different body sites in children with different allergic diseases will be characterized according to the microbiome.

Then, we want to figure out inter- and intra-individual differences with reference to the microbiome,

• that the development of tolerance is associated with a certain microbiome, and
• that knowledge about compositions of bacteria in the airway, gut or skin microbiome can become relevant for developing novel secondary prevention tools for allergic diseases

First step: Samples of the different body sites (mainly nasal and throat swabs from patients with asthma; stool and skin swabs from patients with food allergy) are collected, and the DNA of these samples is used for 16S rRNA gene sequencing. 16S rRNA gene sequencing is a well-established method for studying taxonomy (the kind of bacteria and the quantity of the respective kind) and phylogeny of samples from complex microbiomes. The most representative sequences, so called operational taxonomic units (OTUs), will be determined after sequencing and then be used for statistical analyses.

Second step: The different phenotypes (allergic diseases) and different body sites will be characterized in respect of the main bacteria and other microbial signatures like e.g. diversity of bacteria. These microbial features are compared a) between patients in progression and patients in remission of disease (interindividual comparisons) and b) between time points before and after tolerance development in patients (intraindividual comparisons) with different methodological approaches.

Third step: Microbial features are analyzed in combination with other laboratory markers coming from genetic, epigenetic or immunological examinations. Different cross sectional and prospective cohorts will be available to do this.

As main result, the identification of microbes involved in the processes of progression or remission will enable us to find new possible targets in the secondary prevention and maybe even treatment of allergic diseases. We also will see if/how bacteria are related to other biomarkers.

The Team is an interdisciplinary research group with the aim to get deeper insights into the protective effects on asthma. Professor von Mutius' working group has been actively involved in design, implementation and data analysis of many large, Pan-European multicenter and interdisciplinary projects, including birth cohort studies, addressing the role of genetic and environmental, particularly microbial factors for the development of asthma and allergic diseases. One prominent example of the possible prevention of asthma pathogenesis is the so-called hygiene hypothesis.

The group includes pediatricians, biostatisticians and data manager and is supported by further members of the research group of Prof. Dr. Dr. h.c Erika von Mutius.