Genetic protection against chronic intestinal diseases: New therapeutic approaches!

Genetic protection against chronic intestinal diseases: New therapeutic approaches!

There are currently two million people living with inflammatory bowel disease (IBD) in Europe, and the number is continually increasing. A remarkable study led by the Institute for Clinical Molecular Biology (IKMB) at Kiel University sheds light on the evolutionary basis of these diseases. It shows that a genetic variation, particularly the IL23R variant, was widespread among the first sedentary farmers in Anatolia and continues to influence the risk of IBD to this day.

The study analyzed 251 genomes from the last 14,000 years, paying particular attention to the role of IL23R as a key factor in immune regulation. Reduced function of this gene provides genetic protection against chronic inflammation, which was beneficial to early farmers. Between 10,000 and 12,000 years ago, about 18 percent of the population in Anatolia carried this protective gene variant. Through migration, genetic protection spread to Europe, where it can now be found primarily in southwestern Europe. Currently only five percent of the European population carries the variant uni-kiel.de reported.

Evolutionary biology and modern medicine

The importance of the IL23R variant extends beyond human history. The associated findings are actively used to develop new drugs against IBD. Researchers from genetics, medicine and archeology have come together to shed light on the relationship between genetic factors and inflammatory processes. It becomes clear that chronic inflammation is influenced by complex interactions between genetic dispositions, environmental factors and the microbiome. These findings could help develop personalized treatment approaches for those affected.

Despite advances in immunological research, treatment of IBD remains inadequate for many patients. Many of them rely on surgical intervention, as around 70 percent of Crohn's disease and 30 percent of ulcerative colitis patients require surgery during their lifetime. These operations are often the result of an inadequate response to standardized therapies, which, in addition to the desired effects, often cause significant side effects. What is important here are predictive markers that can be assigned individually. Genotyping can help to develop personalized therapies, especially for drug treatments, such as aerzteblatt.de described in detail.

Key research trends

Current research is investigating, among other things, how inflammatory processes develop in IBD and which genetic factors play a role. The interindividual variability of the microbiome is a key point that deepens the understanding of disease mechanisms. Fecal transplants have shown promising results and have opened up new therapeutic approaches. However, many questions still remain unanswered regarding the ideal donor and dosage form. In addition, novel therapy options are being worked on, such as JAK inhibitors, while the effectiveness of classic treatments such as TNF-alpha blockade is not always guaranteed.

The connection between IBD and other inflammatory diseases, such as rheumatoid arthritis, is also being intensively researched. A disturbed intestinal barrier can trigger joint inflammation and thus lead to an increased burden of disease. This highlights the need to rethink long-standing medical paradigms and develop new, personalized approaches that take both genetic and immunological aspects into account.

Overall, advances in basic research on the pathophysiology of IBD show promising approaches to making treatment more personalized and successful. The symposium “IBD: from pathophysiology to personalized medicine”, which took place on 29/30. March 2019 in Oxford is another example of efforts to advance research in this area.