Irritable bowel syndrome (IBS) affects a significant number of people across the world. In the US alone, roughly 3 million adults have the condition which causes serious gastrointestinal symptoms such as abdominal pain, bloody stools, diarrhea, fatigue, and weight loss.
However, scientists still do not fully understand the exact causes of the disease, which impacts people of all ages, including children. Linked with this knowledge gap is the lack of a cure for the disease, with treatment focused on making lifestyle and diet changes to manage the symptoms.
Now, an interdisciplinary team of scientists working across several European clinics has published the findings of eight years of research into potential biomarkers of the disease, providing vital clues regarding the organic triggers of IBS.
IBS. Image Credit: Panchenko Vladimir/Shutterstock.com
Finding biomarkers by exploring nerve triggers
A European team led by the Technical University of Munich’s Professor Michael Schemann spent almost a decade searching for a putative biomarker of the organic changes that occur in IBS. The current method of diagnosing the disease, which affects around one in six people, is mainly a process of exclusion.
The researchers aimed to uncover a biomarker that would make diagnosis more precise and simple. The team published their findings in the journal PLOS ONE in 2018, which highlight the potential of protease profiling as a valuable strategy for identifying biomarkers of IBS.
Evidence demonstrates that altered nerve function is a major pathogenic factor of IBS. Molecules released in the intestinal by the intestinal mucosa have been shown to trigger the intestinal wall nerves. The study experimentally reproduced this activity by extracting mucosal biopsy supernatants from patients suffering from IBS. In comparison to mucosal biopsy supernatants extracted from controls without IBS, those collected from the patient group showed nerve activation which was absent from the control samples.
Supernatants extracted from patients with ulcerative colitis (UC) in remission were also investigated. The team was interested in investigating this group as UC is considered to be a mild version of IBS and because patients with UC report similar symptoms to IBS, suggesting that the underlying causes of the two illnesses may have significant overlap. The team found, as expected, the supernatants collected from patients with UC also activated neurons.
Additionally, the researchers discovered that proteases were the cause of the nerve activating properties of both the IBS and UC supernatants. These proteases were not just enzymes, the team also uncovered their role as important signaling molecules. One significant difference was found between the nerve activation induced by the IBS and UC supernatants. The team found that the nerve activation triggered by the IBS supernatants was regulated by proteases signaling via the protease-activated receptor type 1, a receptor that was not involved in the nerve activation caused by the UC supernatants.
This key finding encouraged the team to study this particular protein in further detail. Specifically, the team explored the protease levels within the supernatants. The findings revealed that the IBS supernatant presented a specific protein pattern, an IBS-specific protease profile. After running a proteome analysis, the researchers were able to identify 204 proteins that have unique expression patterns in IBS supernatants. In addition, four proteases were identified that were found in elevated levels only in IBS supernatants, in comparison with UC supernatants.
The researchers at the Technical University of Munich questioned how these specific proteins and proteases impact nerve activation. They searched for a method of investigating their influence, experimenting with a protease inhibitor obtained from a strain of the probiotic Bifidobacterium longum. They found that this inhibitor successfully blocked nerve activation induced by the IBS supernatant.
Developing better therapeutic and diagnostic options
The results of the study reveal a protease profile of IBS, which could lead to developing our knowledge of the organic causes of the disease, as well as contribute to the development of new diagnostic methods for the disease, which currently involve a lengthy process of elimination.
Future studies will likely follow up on what was found by the European team. The research, published in PLOS ONE, demonstrates an effective method of identifying biomarkers specific to IBS. Further to providing an effective method of biomarker identification, the team also provides numerous lines of inquiry to follow up in the form of 204 proteins and four proteases that appear in specific patterns in IBS. This could lead to the establishment of better therapeutic options for an illness that affects a significant portion of the population.
- Buhner, S., Hahne, H., Hartwig, K., Li, Q., Vignali, S., Ostertag, D., Meng, C., Hörmannsperger, G., Braak, B., Pehl, C., Frieling, T., Barbara, G., De Giorgio, R., Demir, I., Ceyhan, G., Zeller, F., Boeckxstaens, G., Haller, D., Kuster, B. and Schemann, M., 2018. Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients. PLOS ONE, 13(3), p.e0193943. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193943
- Facts About IBS. International Foundation for Gastrointestinal Disorders. Available at: https://aboutibs.org/what-is-ibs/facts-about-ibs/
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- What is inflammatory bowel disease (IBD)? Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/ibd/what-is-IBD.htm