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Joint study by the DFG Clusters of Excellence PMI and ROOTS shows how we can learn from nature for new therapies.
In Europe alone, approximately two million people live with chronic inflammatory bowel diseases (IBD), and their incidence has been rising steadily in recent decades. However, a small proportion of the European population carries a genetic variant that provides natural protection against IBD. A newly published study in the international journal eBioMedicine explores how this protective variant can be leveraged to develop modern therapies, demonstrating the potential of evolutionary medicine in addressing chronic diseases of the modern era.
The study, led by the Institute of Clinical Molecular Biology (IKMB) at Kiel University, brought together researchers from genetics, medicine, and archaeology. "We have demonstrated that this gene variant, which offers protection against inflammatory bowel diseases, was prevalent among the first sedentary farmers in Anatolia and was introduced to Europe through ancient migration movements," explains Prof. Dr. Ben Krause-Kyora from the IKMB, lead author of the study.
The study, funded as part of the ROOTS and ‘Precision Medicine for Chronic Inflammatory Diseases’ (PMI) Clusters of Excellence, analysed genetic data from 251 human genomes spanning the past 14,000 years across Europe and Anatolia. The researchers focused specifically on the IL23R gene, which plays a key role in immune regulation.
"The exact causes of chronic inflammatory bowel diseases remain unknown. However, previous research has shown that strong immune responses regulated by IL23R are closely linked to these conditions. A reduced function of this pathway appears to provide protection against chronic inflammation," explains Professor Krause-Kyora.
The IL23R variant examined in the study moderates the immune response, preventing excessive inflammation without compromising overall immune function. As a result, individuals carrying this gene variant remain largely protected from infections. "It’s a win-win situation for the body," says co-author Prof. Dr. Dr. Stefan Schreiber, spokesperson for PMI and clinical partner of the research team as a gastroenterologist at the University Medical Centre Schleswig-Holstein.
Around 10,000–12,000 years ago, approximately 18% of individuals in Anatolian farming communities carried this gene variant. The shift from a Palaeolithic lifestyle of hunting and gathering to Neolithic farming likely triggered more frequent inflammatory reactions in individuals. The researchers hypothesise that the IL23R variant provided protection against this heightened inflammatory status, enhancing survival among the first Neolithic farmers. This could explain its high prevalence in early agrarian societies.
From the Neolithic period onward, migratory movements gradually spread the IL23R variant across Europe over the past 8,000 years. Subsequent population admixture led to its highest prevalence in Southwestern Europe and lowest in Northeastern Europe. Interestingly, this distribution mirrors the regional prevalence of IBD, which is most common in Northern and Eastern Europe. Today, approximately five percent of the European population still carries the variant.
The study sheds light on the history of a gene variant that remains medically significant today. "We now understand why a reduced function of IL23R provides protection against inflammatory conditions. The mechanism by which this variant prevents chronic inflammatory bowel diseases has recently been applied in the development of IBD medications. These treatments are considered highly effective with minimal side effects. This example illustrates how we can draw inspiration from nature to develop new therapies," says Stefan Schreiber.
Institutions involved in the study:
• Institute of Clinical Molecular Biology at Kiel University
• Borstel Research Centre
• University of Lübeck
• Institute of Medical Informatics and Statistics at Kiel University
• Department of Food Engineering, Izmir Institute of Technology (Turkey)
• Department of Internal Medicine I, University Medical Centre Schleswig-Holstein, Campus Kiel
• Archaeological Civilisation Disease Consortium (ACDC)
Funded by the German Research Foundation as part of the Clusters of Excellence ROOTS (EXC 2150) and PMI (EXC 2167)
Prof. Dr. Ben Krause-Kyora
Institute of Clinical Molecular Biology of Kiel University
Tel.: +49 431 500-15168
b.krause-kyora@ikmb.uni-kiel.de
Ben Krause-Kyora, Nicolas Antonio da Silva, Elif Kaplan, Daniel Kolbe, Sabine Schade-Lindig, Joachim Wahl, Carola Berszin, Michael Francken, Irina Görner, Kerstin Schierhold, Joachim Pechtl, Gisela Grupe, Johannes Müller, Inken Wohlers, Hauke Busch, David Ellinghaus, Amke Caliebe, Efe Sezgin, Almut Nebel, Stefan Schreiber (2025): Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern Europeans.
eBioMedicine, Volume 113, 2025, 105591, https://doi.org/10.1016/j.ebiom.2025.105591
http://www.precisionmedicine.de The PMI Cluster of Excellence
http://www.cluster-roots.org The ROOTS Cluster of Excellence
https://www.ikmb.uni-kiel.de/ The Institute of Clinical Molecular Biology of Kiel University
Artistic illustration of the connection between changes in lifestyle at the beginning of the Neolith ...
Petra Horstmann
Cluster ROOTS/Uni Kiel
Today, ancient DNA (aDNA) can be extracted from the bones and teeth of people who lived thousands of ...
Jan Steffen
Cluster ROOTS/Uni Kiel
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