Existing scientific knowledge
I. The Challenge
Burden due to Chronic Inflammatory Diseases
¬Almost all organs and tissue can become chronically inflamed and thus produce very different symptoms. The barrier organs, in particular, the intestine, skin and lungs, which come in direct contact with the environment, are affected particularly frequently. Diseases caused by chronic inflammation are not trivial matters. Over the long term, chronic inflammation can in some cases lead to heart attacks, strokes, other cardiovascular events, or even bone fractures. Tissue damage, chronic pain, and mental suffering significantly impact a person’s quality of life. Acute flare-ups and hospital stays lead to a temporary or even total incapacity to work.
Suffering and Costs
¬It is estimated that approximately 10% of the population of Europe suffers from inflammatory diseases. They are also associated with substantial costs. On the one hand, these costs are incurred due to both medical and non-medical treatment. On the other hand, economic costs for society result from the loss of productivity due to the absence from work as a consequence of these illnesses, because inflammatory illnesses often affect younger or middle-aged people that society relies on to fill roles in education, work, and family.
II. The Innovation
Initial Disease Control through New Medications
¬Chronic inflammatory diseases are currently incurable. However, the symptoms of the affected can often be significantly alleviated. Major progress has been made in the past 15 years. Therapy has been virtually revolutionized through the introduction of agents that inhibit overactive inflammatory messengers in a targeted manner. The first agents of this kind were biotechnologically produced antibodies of the inflammatory messenger TNF-α. This biologic enables many patients who were treated with these antibody therapies to suppress the inflammatory activity in the intestine, on the skin, or in the tendons and joints over the long term. The TNF-α blockade has a positive effect on the course of the disease and enables many of those who are affected to lead an almost normal life. The physicians who provide treatment for chronic inflammatory diseases do not need to prescribe medications containing cortisone as often for the acute treatment of a flare-ups. Patients affected with rheumatism require artificial joints less often and are out sick from work less often. Psoriasis therapy has likewise been significantly improved through biologics. The TNF-α blockers were only the beginning of a whole series of novel agents. Over the past few years, a much better understanding of chronic inflammatory diseases has been gained, many new principles of action were discovered, and new drugs have been approved for many of the diseases, enabling a targeted therapy.
¬Furthermore, there is hope for people with the autoimmune disease lupus erythematosus, or lupus for short. While previous biologics did not make any progress in the treatment of lupus, a new biologic – an interferon-α – has shown efficacy in studies. A completely new, pioneering therapy principle for lupus is the stimulation of immune cells with very low doses of interleukin-2.
III. The Causes
Influences from the Environment and Lifestyle
¬Research in the cluster has contributed significantly to better understanding the molecular processes involved in chronic inflammation. This is just one reason why the development of new treatment options is progressing steadily. But one puzzle still remains unsolved: Why have vital immune reactions gotten out of control for so many people, resulting in chronic inflammation? It is known that there is a complex genetic basis. The Cluster of Excellence has played and continues to play a significant role in the elucidation of the genetic factors. Nevertheless, the genetic risks inherited at birth do not yet explain why these cause diseases in some people over the course of their lives and not in others. The analysis of significant environmental influences is thus an additional important field of research – an important key to prophylaxis may be found here. In fact, life conditions, which in the western world have changed significantly from earlier times, may play a decisive role. Because it is almost exclusively people in industrial nations who are affected by diseases such as neurodermitis and psoriasis, Crohn’s disease, asthma, or rheumatism.
¬Why one person gets sick and another does not is currently still unclear. To date, only the negative influence of smoking has been definitively proven to affect the development and course of some chronic inflammatory diseases. It is becoming increasingly clear that an excess of fat tissue promotes chronic inflammatory processes. The consumption of sugar, in particular in the form of fructose, such as from drinking soft drinks, also has a negative effect on immunology. Finding additional triggering factors is an important research objective. Triggers that are currently suspected include, for example, an altered spectrum of infections in childhood and an increased use of antibiotics as well as the drastically altered nutritional and hygiene habits or even the composition of intestinal flora.
¬With the objective of identifying risk factors and predictors for chronic inflammatory intestinal diseases (or chronisch-entzündliche Darmerkrankungen) the ced family study was launched in Kiel. By following those affected by ced and their relatives over the long term in a scientific manner, lifestyle and dietary habits will be revealed that are associated with the development of their disease.
Important Objectives of the Study
There are three points that are important in connection with a successful treatment and are thus the focus of current studies:
IV. The Microbiome
An Important Control Hub for Maintaining Health
¬Humans are not alone: Trillions of bacteria and other microorganisms live in and on our bodies. The totality of all microorganisms in and on a person is known as the microbiome. The bacterial community in the intestine comprises an average of 500 to 1,000 different species and weighs up to two kilograms (4.4 lbs.). But it is not only the intestine that has been colonized; all internal and external boundaries, such as the lungs, mouth, nose, and skin are “inhabited” millions of times over.
However, the microorganisms are in no way ballast and are normally not dangerous either. On the contrary: They are often beneficial, help in digestion or provide vitamins, for example, and they influence the immune system. The composition of the microbiome differs strongly from person to person (and also from laboratory mouse to laboratory mouse). And the differences appear to be associated with the development of chronic inflammatory diseases. It is suspected that patients with chronic intestinal diseases develop immune responses against the body’s own microbiome. It is also noteworthy that their intestinal flora is comprised of fewer species of bacteria than those of healthy persons. Over the last 100 years, the microbial biofilms in the intestine may have also generally changed their structure, for example, through altered dietary habits and hygiene measures.
¬In a widely-noted study from 2012, it was able to be demonstrated that a lack of the essential amino acid tryptophan impairs the immune system in the intestine. This causes the composition of the bacteria colonies in the intestine to change and results in the body becoming more susceptible to diarrhea and inflammation. A diet rich in tryptophan was able to alleviate symptoms of inflammation in mice. The composition of the intestinal bacteria normalized, the inflammations subsided, and the animals became less susceptible to a new disease. These results gave rise to the idea of preventing chronic inflammation in the intestine through the targeted administration of nutrients. One cluster project is busy working on implementing this idea. However, the participating working groups are concentrating not on the amino acid tryptophan, but rather on a product of the metabolism of tryptophan: Niacin, a generic term for the vitamins nicotinic acid amide and nicotinic acid. Niacin was also shown to improve intestinal inflammation in animal tests. What is crucial is that the vitamin reaches the large intestine in larger quantities and does not pass over into the blood. A patented “package” ensures that niacin is released in a targeted manner in the large intestine. Studies on healthy volunteers confirm that the microencapsulation of the niacin developed by the cluster works as desired.