Shedding light on the transition to disease

Joint press release by Charité and the Max Delbrück Center What if people never developed diseases in the first place? What exactly occurs during the transition from health to disease? What do inflammatory precursors of disease tell us? And how do interactions between nutrition and the gut microbiome influence the immune system? Under the direction of researchers at Charité – Universitätsmedizin Berlin and the Max Delbrück Center, scientific teams in Germany and several other European countries are looking for strategies to preserve health and detect diseases in their early stages. The European Union is funding the IMMEDIATE project to the tune of over €7 million over the next four years. Chronic inflammation is the root cause of many organic diseases. Yet what happens at a molecular level in the body during this transition from health to illness is still largely unknown. With their project IMMEDIATE, European and Israeli researchers now want to shed more light on these poorly understood processes and find out to what extent nutrition and the gut microbiome could be altered to prevent diseases from developing in the first place. IMMEDIATE is an acronym that stands for Imminent Disease Prediction and Prevention at the Environment Host Interface. In order to be able to evaluate an individual’s disease risks and intervene in time, the project seeks to find measurable indicators – called biomarkers – during the course of its work, explains Prof. Friedemann Paul, leader of the project and director of the Experimental and Clinical Research Center (ECRC), a joint institution of Charité and the Max Delbrück Center: “First, we want to better understand the inflammatory processes that precede organ dysfunction or damage. We also want to identify biomarkers that we can use to detect processes even before disease symptoms appear.” For their investigations, the researchers will employ methods including state-of-the-art omics technologies and make use of clinical data and biosamples from three ongoing observational studies. “These studies are the German National Cohort (NAKO) and a cohort of patients who have received kidney transplants and thus have virtually “normal” kidney function, as well as an Israeli cohort,” adds Dr. Chotima Böttcher from the ECRC, who is helping to coordinate IMMEDIATE. Prof. Tobias Pischon’s lab at the Max Delbrück Center will contribute to the project by conducting extensive proteome analyses. His team wants to obtain detailed information on many different inflammation markers and identify molecular signatures associated with changes in cardiovascular and renal function as well as metabolism. The researchers will then investigate the similarities and differences between these signatures in different diseases. In parallel, Dr. Sofia Forslund’s lab at the Max Delbrück Center and ECRC will look at whether a particular gut microbe can reduce inflammation. “Our goal is to understand how and why interventions such as dietary changes and the administration of special microbiota change the composition of the gut microbiome – and how the metabolic products of the microbes influence the immune system,” explains Dr. Forslund. The hope is that this knowledge can then be translated into a targeted approach for preventing disease and promoting health. Dr. Forslund’s team will develop the necessary infrastructure and analytical methods to pull together the huge amounts of data generated by omics technologies and evaluate these data with the help of artificial intelligence. Other Charité scientists and research labs at Campus Berlin Buch are involved in this large-scale analysis project, including Dr. Philipp Mertins’s Proteomics Lab, Dr. Jennifer Kirwan’s Metabolomics Lab, Dr. Nicola Wilck’s Immune-Microbial Dynamics in Cardiorenal Disease Lab, and Dr. Anja Mähler’s Clinical Research Unit. In a next step, the results of the investigations and analyses will be tested in practice. The IMMEDIATE consortium is therefore planning its own intervention studies, including a study with around 200 hospital workers. “These test subjects are often under a great deal of stress due to their job and usually eat rather unhealthily and at irregular times,” presumes Böttcher. “So we suspect that they will have elevated inflammation levels.” One thing the researchers want to find out is whether the administration of the anti-inflammatory microbe Akkermansia muciniphila can change the biomarkers of the test subjects and improve their general well-being. Mobile apps developed by the IMMEDIATE team in cooperation with patient advocacy organizations will help gather information. The apps provide feedback and tips to help the users integrate proven health-promoting measures into their own lives – enabling changes to be made before they even reach the disease threshold. Read More 

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