Blood-Based Biomarkers for Diagnosing IBS-D
When patients present with symptoms of chronic diarrhea, physicians often determine it to be either irritable bowel syndrome with diarrhea (IBS-D), inflammatory bowel disease (primarily Crohn’s disease and ulcerative colitis), and/or celiac disease. While highly accurate testing for celiac disease and inflammatory bowel disease (IBD) is available, screening for IBS lags behind as it relies on symptom-based diagnostic criteria and elimination of other diagnoses, which can be less accurate and take longer than a diagnostic test.
However, researchers have made advancements in developing alternative methods to diagnose IBS and further uncovering its pathogenesis. For instance, in our previous newsletter we discussed a urine-based biomarker test.1 In this edition, we return with an overview of another biomarker test for this condition. After identification, validation, and enhancement, a group of scientists have successfully established blood-based biomarkers that can differentiate irritable bowel syndrome with diarrhea (IBS-D) from inflammatory bowel disease (IBD).
IBS is a chronic disorder with symptoms ranging from abdominal pain and bloating, to constipation and/or diarrhea. It is the most common gastrointestinal condition suffered by individuals worldwide. There are three main subtypes of IBS: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and IBS with both constipation and diarrhea (mixed) (IBS-M). Lifestyle and dietary modifications greatly aid in symptom management, while some prescribed and over-the-counter medications are also useful.
IBD is a term that primarily refers to two diseases of the intestine: Crohn’s disease and ulcerative colitis. In Crohn’s disease, inflammation occurs in any part of the digestive tract and any depth of the bowel wall. In ulcerative colitis, on the other hand, inflammation is limited to the inner mucosa of the large intestine, beginning at the anus and spreading upward into the colon. The most common symptoms of IBD are diarrhea, abdominal pain, fever, rectal bleeding, weight loss, and anemia. Physicians typically diagnose IBD via endoscopy and treat it with a variety of strong medications.
While IBS and IBD are two distinct gastrointestinal conditions, many individuals mistake them for each other. With that said, it is clear to see how confusion arises between IBS-D and IBD when they both have diarrhea as a common symptom.
Implications of Validated Biomarkers for IBS
With the identification of two biomarkers called anti-vinculin and anti-cytolethal distending toxin B (anti-CdtB) from blood testing,2 researchers from the study built on their findings in a later analysis,3 significantly improving on the accuracy of the test. Not only do these biomarkers distinguish IBS-D from other digestive conditions with symptoms of chronic diarrhea, but they also aid in the diagnosis of IBS-D in new patients. Interestingly, their findings also provided some evidentiary basis for questioning the dominating viewpoint that IBS is a functional disorder caused by hyper-sensitivity to the nervous system, gut bacteria, and psychological factors (i.e., stress). They hypothesize that the condition – or at least a subtype – is rooted in biological interaction, signifying directions for therapeutic treatment.
The results of their studies address a critical gap in clinical practices for IBS, potentially transforming current diagnosing methods to blood sampling. This presents great potential in reducing healthcare costs derived from exclusionary tests for IBS, as well as patient fatigue. These biomarkers can also be crucial for patients with both IBS and IBD, where ongoing chronic diarrhea may actually be a result of IBS, and may be concealing recovery in IBD.
Studies have increasingly found that gastroenteritis is a likely cause for a subset of IBS, called post-infectious IBS (PI-IBS), which affects as many as 5-32% of those who have had gastroenteritis.4 The primary trigger for gastroenteritis, an inflammation in the stomach and intestines, is infection with bacteria such as Campylobacter jejuni, Escherichia coli, Salmonella, and Shigella. A common toxin among these infections is cytolethal distending toxin (Cdt). Cdt has three subunits called CdtA, CdtB, and CdtC. Researchers focused on CdtB because this toxin interacted with a host protein called vinculin, which translates and regulates the essential movements of biochemical properties between the receptors of the cell and its cytoskeleton, constantly interacting with the cell’s inside and outside microenvironment.2
Scientists found that anti-CdtB and anti-vinculin were significantly elevated in IBS-D patients compared to participants who were healthy and did not have any history of digestive illnesses, participants with IBD (Crohn’s disease and ulcerative colitis), and participants with celiac disease. Meanwhile, these biomarkers were equal and/or similar between healthy controls, IBD patients (Crohn’s and colitis), and celiac disease patients, presenting no statistically meaningful differences.
It is important to note that these biomarkers are not found in all IBS-D patients. However, this subgroup of patients and further understanding of the specific pathogenesis for IBS can lead to the development of therapies to aid patients in their management of chronic diarrhea.
Increasing Diagnostic Power
The researchers conducted a follow-up study in 2019,3 during which they noticed that the biomarkers’ epitopes are easily subject to damage due to sensitivity to environmental changes such as heat and pH levels. These damages make it difficult to identify and, in some cases, hide the biomarkers in blood samples. To address this, they added a step to the biomarker testing process by stabilizing the epitopes (proprietary epitope stabilization). This greatly enhanced the test by increasing its specificity and sensitivity to a probable accuracy of greater than 98% in diagnosing IBS and more than 90% in distinguishing IBS and IBD patients.
Implementation in Clinical Practice
The researchers acknowledge that there are demographic limitations (such as the lack of inclusion from seniors greater than 65 years of age and Asian populations) encountered in their studies that need to be addressed in future research. However, this should not stray from the significance of their findings as well as the fact that other studies have confirmed the value of the biomarkers anti-CdtB and anti-vinculin since its validation in the 2015 study. In addition, researchers posit that the path forward is to assess the feasibility of implementing the test in clinical practice by conducting cost-analysis between current diagnosing methods and real-world application of the test.
How You Can Get Tested for IBS
The blood test for irritable bowel syndrome is now available in Canada and the US under the name ibs-smart™. To learn more, visit their website at www.ibssmart.com. If you reside in Canada, you can find a patient-directed process at www.ibssmart.com/canada. You can order the test online. The ibs-smart™ kit and requisition form must be completed by your treating physician, and then shipped to labs for analysis. They send the results to your physician within four business days of receiving the blood samples.