We aim to ​make major breakthroughs in our understanding of immune-mediated, autoimmune and infectious diseases by bridging the gap between the disease genotypes and the disease phenotypes; the immune dysregulation seen in infectious diseases can be seen as the opposite to immune-mediated diseases.

By studying these two extremes we will be able to enhance our understanding of how an imbalanced immune system leads to disease in gastrointestinal immune-mediated diseases.

Three model diseases
We study three model diseases: two chronic inflammatory intestinal diseases (celiac disease and IBD (Crohn’s disease and ulcerative colitis)) and one infectious disease (systemic candidemia).

All three diseases are complex in nature as they are caused by an interaction between multiple genetic and non-genetic factors and involve the host immune system. Celiac disease is characterized by a dysregulated immune response to the dietary protein gluten, while IBD is characterized by a dysregulated immune response to commensal microorganisms.

In 3GI we use these model diseases to work on the crossroads of three of the major research topics in science at the moment:

  1. The genetics of complex diseases
  2. The influence of genetic risk factors on the host immune system 
  3. The role of the gut microbiome on disease development and progression
Relevance

How our research benefits to society

Chronic immune-mediated and autoimmune diseases​ affect about 5% of the population in Europe and North America, with two thirds of the patients being female. The increase in immune-mediated diseases accounts for a large part the complex immune-mediated diseases affecting the gastrointestinal tract:

  • celiac disease,
  • Crohn’s disease,
  • ulcerative colitis.

Translate genetic findings into clinical use

Recent advances in genetic studies reveal a vast majority of the underlying genetic risk factors and unequivocally show that gastrointestinal immune-mediated disease share part of their genetic and immunological background with diseases like rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and multiple sclerosis. The challenge we are currently facing is to translate these genetic findings into clinical use.

Our findings will lead to:
  • Biomarkers to identify patients before disease onset or to monitor disease progression and remission;
  • New drug targets or evidence for repurposing existing drugs to other disease;
  • Insight into how the gut microbiome can be modified through pre/ pro or anti-biotics to treat or prevent disease.
  • We explore prospective patient cohorts as well as the LifeLines cohort study to identify signatures of biomarkers,. These biomarkers are based on e.g.

    • the gut microbiome and miRNAs, to test genetic risk profiles;
    • the known genetic risk factors, to understand the role of environmental factors on disease risk;
    • smoking and diet -using prospective cohort data. 

    This way we investigate the combined effect of genetic risk variants and e.g. the gut microbial composition on disease development and outcome.

  • The gut microbiome is also seen as a potential modulator for disease treatment through the use of probiotics or by the development of prebiotics.3GI also works on downstream functional analyses of identified disease-specific genetic variants and in particular how they affect the transcriptional regulation of disease-specific cell-types.

    Unraveling the disease-specific transcriptional networks and their corresponding biological pathways is a crucial first step for identifying targets for further drug development. Since the gut is central to the development of many immune mediated and infectious diseases and connects and integrates organ systems throughout the body, the work that is being done within 3GI has far-reaching consequences in health and disease of future patients.