Biomarkers in irritable bowel syndrome (IBS) can guide more targeted therapy in a very multifactorial disease. However, no generally accepted biomarkers exist for an accurate diagnosis of IBS, leaving gastroenterologists to rely on symptoms and conversations with patients.
In a study1, Michael Camilleri, MD, from the Mayo Clinic in Rochester, Minnesota, and colleagues evaluated daily stool frequency and consistency of bowel movements—based on the Bristol Stool Form Scale—, fecal bile acids, and fecal fat/weight of 94 patients with IBS to determine biomarkers of clinically significant diarrhea or constipation based on stool frequency, consistency, and weight.
The researchers found that fecal bile acids and fecal fat are accurate biomarkers associated with significant bowel dysfunction among patients with diarrhea predominant irritable bowel syndrome (IBS‐D) and constipation predominant irritable bowel syndrome (IBS‐C).
Gastroenterology Consultant caught up with Dr Camilleri about the research.
Gastroenterology Consultant: What is the current clinical need for biomarkers for IBS-D and IBS-C?
Michael Camilleri: At the present time, the state-of-the-art is that patients with either constipation or diarrhea-associated IBS are subjected to a series of therapeutic trials without trying to find out what is the underlying cause of the bowel dysfunction. So, validation of biomarkers provides an opportunity to be much more specific in our choice of therapy. This is important because we now have evidence, not just our study conducted at Mayo Clinic, but in the entire published literature from several countries, that about 1 in 3 or 4 patients that have what would be called IBS-D actually have bile acid malabsorption. This means that some of the bile acids that are normally absorbed in the small intestine actually get into the colon and there they induce either water secretion or induce contractions that result in the diarrhea. We have been working to try to develop tests that will allow us to identify, among the many patients we see with IBS symptoms, whether there is an underlying cause for their diarrhea. This is important because there are some very specific things we could do to neutralize those bile acids by binding or sequestering them within the lumen of the colon and thus prevent them from causing secretion or inducing contractions that result in the diarrhea. With regards to constipation, although this is not the major focus of our recent papers, there is evidence that up to 10% of patients with constipation-dominant IBS have the opposite, that is they have a deficiency of bile acids getting into colon. For these two reasons, we have pursued this bile acids as a biomarker for either constipation or diarrhea. The main indication for measuring these biomarkers at the present time is to identify the patients with diarrhea.
GASTRO CON: How do current approaches lack in differentiating mild from severe alterations of bowel function, rendering them sub-optimal strategies for treatment?
MC: The only approach used by most gastroenterologists is an appraisal of symptoms. There are no generally used biomarkers that lead to logical, targeted treatment of the identified dysfunction. The only two actionable biomarkers that I believe have implications for treatment are the fecal bile acid excretion, the focus of the current study, and the rate of movement of content through the colon. At the present time, by just asking patients the number of bowel movements per day or the average consistency of bowel movements, it is not clear what the underlying cause is and how is it best treated. What we are trying to do is to give much more precise treatments to patients, individualizing treatment based on these two actionable biomarkers.
GASTRO CON: Are fecal weight, stool consistency, and frequency of bowel movements already measured regularly in a clinical setting?
MC: Fecal weight is not measured regularly in a clinical setting, but frequency of bowel movement and consistency based on a scale is regularly done but they are merely a bit more quantitative than symptom description.
GASTRO CON: What are the clinical implications of your study and how can a gastroenterologist apply this to practice?
MC: The first and most important thing is that the tests included in the study are now available through a mail-in stool sample. Any gastroenterologist around the country who wishes to find out whether their patient with diarrhea actually has a problem with the bile acids can do a collection just as we have done in by measuring fecal fat excretion in patients with diarrhea for the last 50 years. On the same stool sample, which is collected over 48 hours, you can also measure the bile acids. In another recent paper2, we have identified three diagnostic criteria to diagnose bile acid diarrhea based on different cut-offs of the total and individual bile acids. Thus, based on total bile acid excretion and the types of bile acids appearing in stool (particularly when the percentage of primary bile acids in stool exceeds 10%), one can then make a diagnosis of bile acid diarrhea and then treat specifically with one of the bile acid sequestrants on the market: cholestyramine, colestipol, and colesevelam. What we are trying to do is to move towards a more individualized way to treat patients.
GASTRO CON: What are the next steps of your research?
MC: One of the next steps is to try to validate whether we can simplify this test by using a single, random stool sample with a detailed measurement of the types of bile acids; we need to assess whether this biomarker has the same accuracy. Another thing we have also been working on is a study to estimate the number of colonoscopies and CT scans and MRIs that are avoided if we can achieve the diagnosis sooner with the fecal bile acid measurement.
References:
- Vijayvargiya P, Camilleri M, Burton D, Busciglio I, Lueke A, Donato LJ. Bile and fat excretionare biomarkers of clinically significant diarrhoea and constipation in irritable bowel syndrome [published online February 10, 2019]. Aliment Pharmacol Ther. 2019;49(6):744-758. doi:10.1111/apt.15106.
- Vijayvargiya P, Camilleri M, Chedid V, et al. Analysis of fecal primary bile acids detects increased stool weight and colonic transit in patients with chronic functional diarrhea. Clin Gastroenterol Hepatol. 2019;17(5):922-929. doi:10.1016/j.cgh.2018.05.050.
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