Cluster of Excellence ROOTS - Social, Environmental, and Cultural Connectivity in Past Societies
Artistic illustration of the connection between changes in lifestyle at the beginning of the Neolithic period and the frequency of chronic inflammatory bowel diseases today .
Credit: Petra Horstmann, Cluster ROOTS/Uni Kiel
In Europe alone, approximately 2 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 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, part of the ROOTS and "Precision Medicine for Chronic Inflammatory Diseases" (PMI) Clusters of Excellence, analyzed 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.
Credit: Jan Steffen, Cluster ROOTS/Uni Kiel
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 Center Schleswig-Holstein.
About 10,000–12,000 years ago, approximately 18% of individuals in Anatolian farming communities carried this gene variant. The shift from a Paleolithic lifestyle of hunting and gathering to Neolithic farming likely triggered more frequent inflammatory reactions in individuals.
The researchers hypothesize 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 5% 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 Schreiber.
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 Center Schleswig-Holstein.
About 10,000–12,000 years ago, approximately 18% of individuals in Anatolian farming communities carried this gene variant. The shift from a Paleolithic lifestyle of hunting and gathering to Neolithic farming likely triggered more frequent inflammatory reactions in individuals.
The researchers hypothesize 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 5% 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 Schreiber.
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