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The search for the causes of inflammation

What are the triggers and the early signs of chronic inflammatory bowel diseases (IBD)? Finding this out is the aim of the IBD family study. Diet, lifestyle and intestinal bacteria are particularly focused on.

Centrifuge with samples
© pur.pur

In a centrifuge like this one, blood and stool samples from patients and their healthy family members are prepared for further analysis.

An estimated  400,000 people in Germany  have a chronic inflammatory bowel disease. The two most common forms are Crohn's disease and ulcerative colitis. Among other things, patients suffer from severe, prolonged diarrhoea, severe abdominal pain and general physical weakness. Why the bowels become inflamed again and again with Crohn's disease and ulcerative colitis has not been definitively determined. But one thing is clear: the diseases do not have a single cause, but develop due to a genetic predisposition in combination with environmental and lifestyle factors. A disturbed intestinal barrier (i.e. protection against germs and other harmful substances from the intestine) also plays a role.

We want to understand more clearly what contributes to the fact that some members of a family fall ill with IBD, while others stay healthy.

Wolfgang Lieb

Finding the triggering factors is an important research goal: “They are the key to prevention,” emphasised Professor Wolfgang Lieb, head of the Institute of Epidemiology. Suspected factors include a different spectrum of infections in childhood and an increased use of antibiotics, as well dietary and hygiene habits, and the composition of the intestinal flora.

The IBD family study began in Kiel in 2013, with the aim of identifying risk factors and predictors for chronic inflammatory bowel diseases. The study includes patients with corresponding diseases, as well as their parents, children and siblings. In comparison with the general population, first-degree relatives have a 10 to 20 times higher risk of disease.

Researcher in a laboratory
Photo: pur.pur

A special focus of the study is analysis of the intestinal microbiome

 

Through long-term scientific monitoring of healthy members of the family, lifestyle and dietary habits should be revealed which are associated with the development of the disease. Blood and stool samples are analysed for markers, which could predict the outbreak of the disease. “With our approach, we can scientifically monitor healthy people who have a slightly increased chance of developing IBD over the long term,” explained Lieb, who is also a board member of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI).

“We want to understand more clearly what contributes to the fact that some members of a family fall ill with IBD, while others stay healthy,” explained Lieb. Also, studying healthy individuals offers the possibility to detect the first signs of the disease, which pre-date the symptoms. “That is why we collect lifestyle data, health data and biological samples from the family members on a regular basis,” added the study coordinator Dr Janna Enderle. If a person becomes ill during the course of the study, the researchers can investigate whether the biological samples collected before the onset of the disease already contain abnormalities which could serve as a kind of early warning system. Currently, the study comprises around 2,000 patients and 2,000 family members.

A special focus of the study is analysis of the intestinal microbiome, i.e. the totality of microorganisms in the intestine. The microbial colonisation of the intestine in patients with IBD is significantly altered in comparison with the overall population, and in particular, the diversity of the species is reduced. It is unclear whether these changes are the result or the cause of the disease. “We hope to find a kind of biomarker in the stool,” explained Dr Corinna Bang, head of the microbiome laboratory at the Institute of Clinical Molecular Biology. “If the changed intestinal microbiota trigger disease, then this opens up a new treatment option. And if they are a symptom of the disease, that would be useful in terms of diagnostics.” The detailed examination of the stool samples is not yet complete. But there is already one result: clinically healthy relatives of IBD patients also have reduced diversity in their microbiome.

During the first years of the study, four people became ill with IBD, who were still healthy at the start. The detailed analyses of the stool and blood samples of these new cases are still ongoing. Bang said “We have discovered that certain inflammation markers in the stool, such as calprotectin, were already increased at the beginning of the study, when the individuals concerned were still healthy.”

Author: Kerstin Nees

Chronic inflammatory bowel disease

With Crohn's disease, the inflammation can affect the entire digestive tract, from the mouth to the anus. With ulcerative colitis, only the mucous membrane of the large intestine becomes inflamed. The diseases very frequently emerge from the age of 15 to 35, and usually progress in relapsing-remitting form. During acute relapses, patients suffer from frequent severe diarrhoea and severe abdominal pain. Fever, flu-like symptoms as well as weight loss, persistent fatigue and lack of energy are common accessory symptoms. Inflammation can also occur in other parts of the body, for example in the skin, joints or eyes.

For around two decades, the study of chronic inflammatory bowel diseases has been a priority research area in Kiel. Researchers at the Cluster of Excellence PMI and its predecessor cluster “Inflammation at Interfaces” have been and still are significantly involved in determining the genetic factors and molecular disease mechanisms. ne

CED Family Study