Different diseases - common metabolic pathways

The results argue for a comprehensive approach to disease prevention. The scientists have now published their findings in the journal Nature Medicine.

Many elderly people suffer simultaneously from several, frequently very different diseases, a condition also known as multimorbidity. Their quality of life is severely restricted, and they receive medication from different doctors, a process which is difficult and often insufficiently coordinated. Observations indicate that certain diseases commonly occur together, but the causes of this are largely unknown.

In a recent study, a team led by Dr. Claudia Langenberg, BIH Professor of Computational Medicine, and scientists from Munich and the United Kingdom have now identified a number of metabolic processes that are associated not only with one, but simultaneously with up to 14 diseases. The scientists analyzed data from more than 11,000 participants in the EPIC-Norfolk prospective cohort study. This records hundreds of measurements from blood samples, as well as clinical data on diseases over more than 20 years of follow-up.

"We wanted to know whether there are certain markers in the blood that indicate a risk, not only for one but for several diseases at the same time," Langenberg explains. To do this, the scientists first examined the concentration of hundreds of different molecules in the blood samples of a total of 11,000 study participants. They then examined how the concentration of individual metabolites was related to the onset of a total of 27 serious diseases in the participants. The metabolites included not only known metabolic products such as sugars, fats and vitamins, but also substances whose concentration depends on genetic or environmental factors. For example, the scientists were able to detect the degradation products of medications, coffee consumption or the presence of gut bacteria using a process known as "molecular profiling."

The blood samples had already been taken from the participants more than 20 years ago and been stored at minus 196 degrees Celsius since then. At that time, the people were mostly healthy. The diseases they developed afterwards were systematically recorded in detail for more than 20 years through electronic hospital data. "This allowed us to explore how the concentration of hundreds of molecules in the blood is linked to the development of one or multiple diseases," Langenberg explains.

For example, the team found that the concentration of many metabolites in the blood that were associated with disease onset were explained by impaired liver and kidney function, obesity or chronic inflammation. But they also discovered that certain lifestyle factors or a reduced diversity of intestinal bacteria, also known as the gut microbiome, influence blood levels and can thus provide clues to the development of diseases over time. It turned out that half of all detected molecules were associated with an increased or decreased risk of at least one disease - the majority with multiple, sometimes very different, diseases, pointing to metabolic pathways that increase the risk of multimorbidity.

"We found, for example, that an increased concentration of the sugar-like molecule N-acetylneuraminate increased the risk of no less than 14 diseases," explains Maik Pietzner, a scientist working with Claudia Langenberg and lead author of the paper. "Gamma-glutamylglycine, on the other hand, is exclusively associated with the occurrence of diabetes. Other members of the same molecular groups simultaneously increase the risk of liver and heart disease." Langenberg adds: "Overall, we observed that two-thirds of the molecules are associated with the occurrence of more than one disease. This is in line with the fact that patients often develop a range of diseases in the course of their lives. If we succeed in influencing these key factors, this could make it possible to counter multiple diseases simultaneously."

The scientists' extensive analysis enables insights into the various factors influencing human metabolism that were previously not possible in this level of detail. To make this reference available to scientists around the world, the authors have developed a web application called "omicscience.org." It makes all the results publicly available in graphical form so that they can be used in new studies. Langenberg adds: "The website enables scientists to determine key influencing factors for any molecule they are interested in or to uncover completely new connections between diseases. All of this was only possible due to our systematic, data-driven approach."

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