September 2019 Issue

New Blood Test to Diagnose IBS
By Diana Reid, MPH, RD
Today’s Dietitian
Vol. 21, No. 9, P. 42

Is it a game changer or a case of limited use?

Dietitians who work with individuals who have irritable bowel syndrome (IBS) know that poor quality of life is a significant issue for these patients. Between the complex and sometimes lengthy diagnostic process and the chronic, painful, and often embarrassing symptoms, IBS patients constantly are looking for ways to become better informed about their condition and reduce unnecessary stress and discomfort.1

A new version of a blood test designed to diagnose postinfectious IBS (PI-IBS) recently was announced, presenting a potential opportunity to begin treating IBS patients in a more rapid and targeted manner with dietary, lifestyle, and/or pharmacological treatments. PI-IBS produces the same symptoms as “garden variety” IBS but develops as a result of foodborne illness, leading to bacterial infectious gastroenteritis, characterized by stomach cramps, diarrhea, and vomiting.2

The ibs-smart test, developed by researchers at Cedars-Sinai Medical Center in Los Angeles, takes a unique path to diagnosis. It measures antibodies produced by the body in response to infectious gastroenteritis and can diagnose PI-IBS with up to 98% accuracy.3 The test could offer benefits for health care professionals and patients alike; however, it faces several important limitations.

PI-IBS results from a previous bacterial, viral, or parasitic infection of the gastrointenstinal (GI) tract.4 The path from foodborne infection to PI-IBS is still unclear; however, researchers have suggested these infections may lead to alterations in the gut mucosa, increased intestinal permeability, changes in gut motility, increases in immune system activation and inflammation, reduced absorptive capacity, or reduced digestive enzyme activity.5

Common types of pathogens linked to PI-IBS include Campylobacter jejuni, E coli, Giardia lamblia, Shigella, and norovirus, though other types of bacteria and viruses also have been implicated.6 According to Mark Pimentel, MD, of Cedars-Sinai Medical Center, who helped develop the ibs-smart test, the common link between all of these bacteria and PI-IBS is a single toxin they produce. Called cytolethal distending toxin B (or CdtB), this toxin provokes a strong reaction from the body following ingestion.

There are various factors that may affect whether someone who experiences a severe bout of food poisoning or traveler’s diarrhea will develop PI-IBS. These factors may include the type of pathogen, specific symptoms during infection, and the amount of time elapsed since infection.6,7

A unique hallmark of PI-IBS is activation of the immune system and production of autoimmune antibodies in response to bacterial infection. Two specific antibodies, anti-CdtB and antivinculin, have been found to be elevated in patients with diarrhea-predominant IBS (IBS-D) and mixed IBS (IBS-M)—also called IBS-A, for alternating symptoms of diarrhea and constipation—who previously experienced infectious gastroenteritis.8 Other types of IBS aren’t characterized by these antibodies.

In terms of prevalence, studies have shown that individuals who are exposed to infectious gastroenteritis have a nearly four-fold greater risk of developing PI-IBS than those who weren’t exposed. However, despite the increased risk, on average only 1 in 9 people who experience infectious gastroenteritis will go on to develop PI-IBS.9 Besides bacterial infection, there are many other factors known to be associated with increased prevalence or risk of PI-IBS, such as age, gender, ethnicity, childhood trauma, and psychological stress.10

Typical IBS Diagnostic Process
After decades of IBS being considered a “diagnosis of exclusion” and one fraught with many costly and invasive tests, the Rome IV criteria were developed in 2016, providing a simpler, symptom-based diagnostic rubric. The criteria include recurrent abdominal pain that occurred on average at least one day per week during the past three months, began more than six months previously, and is associated with two or more of the following11:

• defecation;
• a change in frequency of stool; and
• a change in stool appearance.

Physicians and gastroenterologists use these criteria alongside a physical examination, medical and symptom history, and review of food intake and dietary habits to properly diagnose IBS, as well as characterize it as IBS-D, IBS-M, or constipation-predominant IBS (IBS-C).

When “red flag” symptoms such as fever, blood in the stool, unintentional weight loss, malnutrition, or family history of other GI diseases are present, a physician may order additional clinical tests or procedures to help differentiate IBS from other GI disorders.

The Rome IV criteria are quite robust, and with proper dietary, physical, and symptom assessment, unnecessary tests generally can be kept to a minimum. For more complicated cases, or where it’s likely there are overlapping disorders, testing that includes endoscopy, colonoscopy, fecal calprotectin, and others may be required to clarify the diagnosis.

The ibs-smart Test
Physicians can order the ibs-smart blood test, which is marketed by Gemelli Biotech, online for approximately $220. All that’s required of patients is a simple blood draw. Test results will show a positive result for one or both antibodies or an inconclusive result.

An older version of this test was validated as part of a large-scale, 180-center trial (TARGET 3) in 2015. Patients with IBS-D (n=2,375), based on the Rome III criteria, were recruited for the antivinculin and anti-CdtB antibody portion of the trial, along with 142 patients with inflammatory bowel disease (IBD), 121 patients with celiac disease, and 43 healthy controls.

This study, published in the peer-reviewed journal PLoS ONE in 2015, reported a sensitivity of 43.7% and specificity of 91.6% for anti-CdtB, and a sensitivity of 32.6% and specificity of 83.8% for antivinculin in identifying PI-IBS.8 (When the sensitivity or “detection rate” of a test is low, as with this test, it’s an indication that a significant number of people may test negative or have an inconclusive result, even though they have the disease in question. The specificity of a test, when high—usually above 90%, as is the case with this test—indicates the test results will show few false-positives, giving patients great confidence that they have a positive diagnosis.)

Pimentel and his team reported study findings from the most recent version of the ibs-smart test at the Digestive Disease Week conference in San Diego in May 2019. This small follow-up study included results from a random sampling of the initial TARGET 3 multicenter trial, including 84 IBS-D patients and 31 IBD patients. According to Pimentel, with the current version of the ibs-smart test, patients who receive a positive result for both markers (anti-CdtB and antivinculin) have a probability greater than 98% of having PI-IBS. If just one marker is positive, the positive predictive value is greater than 90%. An abstract explaining the study results was published in a special supplement of the journal Gastroenterology,3 and additional study results were published in the journal Digestive Diseases and Sciences, both in May 2019.12

In addition to these two studies by Pimentel and colleagues, additional studies of US military personnel in Latin America and Southeast Asia validated the antivinculin and anti-CdtB markers as predictors of postinfectious IBS-D.13,14

Potential Advantages of a Biomarker for Diagnosis
With regard to patients’ quality of life, the idea of a blood test to quickly diagnose IBS is a dream realized for many who spend years suffering physically and financially before they receive a definitive diagnosis. A survey of more than 2,000 patients with IBS found that, on average, an IBS diagnosis was made seven years after symptoms began,15 and that these patients account for more than 50% of consultations with gastroenterologists globally.11,16 A 2002 study estimated that directed health care costs associated with IBS in the United States exceed $1.3 billion per year, and this number has grown since then.17 Finally, these direct costs don’t take into account those associated with missed work or school and over-the-counter remedies used by patients with IBS.

Given these challenges, administering a test that shortens the diagnostic process could provide peace of mind and significantly save time and money for patients and health care practitioners alike. Pimentel’s team has done some initial studies on cost savings regarding the ibs-smart test and found that each positive test would save a minimum of $800 per patient in the diagnostic process, noting that this figure doesn’t factor in a reduced need for colonoscopies in many situations.

An effective diagnostic test for IBS also may give general practitioners more confidence in diagnosing IBS. Using the Rome criteria and the ibs-smart test, these clinicians could avoid referring patients who don’t need further evaluation to gastroenterologists and begin treatment much sooner.

Drawbacks: Limited Use Case and Complicated Patients
Since IBS is a disorder of multifactorial etiology and PI-IBS represents an estimated 6% to 17% of the total population of IBS sufferers, it remains unclear how broadly applicable the ibs-smart test is, except in cases where patients are confident their symptoms developed following a recent GI infection and they meet the criteria for IBS-D or IBS-M.1,4,9,18

The test can’t diagnose IBS resulting from other risk factors or causes beyond foodborne illness and is inappropriate for individuals who suspect IBS-C, as this form of IBS has a different presentation and isn’t characterized by the antivinculin and anti-CdtB markers.

In addition, there are potential concerns of misdiagnosis, as other disorders such as microscopic colitis also can present with symptoms similar to IBS-D.19,20 In this scenario, a comprehensive clinical diagnostic process is important to ensure proper treatment is implemented.

Finally, many individuals suffer from multiple GI disorders or a combination of gut issues and autoimmune diseases, such as celiac disease, IBD, and food allergies and intolerances. Using a single diagnostic indicator such as a blood test has the potential to miss other serious issues requiring treatment.

Dietitian’s Role
While RDs aren’t directly involved in diagnosing IBS, they often support this process as it evolves. For example, RDs may see patients with GI problems who don’t have confirmed diagnoses and provide firstline dietary treatment, only to find there still are issues to address. For example, a patient may ask about the ibs-smart test and have multiple symptoms that raise red flags, such as bloody stools, unintentional weight loss, or unexplained nutrient deficiencies. In this scenario, recommend they visit their primary care practitioner or gastroenterologist to discuss the test and for further evaluation. Dietitians can consult with their patients’ doctors to discuss next steps.

RDs can follow these additional recommendations when counseling patients:

Make referrals. Dietitians who encounter patients with diarrhea-predominant symptoms or who can recall the origins of their IBS after a trip abroad or bout of food poisoning should refer them to their physicians and the ibs-smart test website to help determine whether the test may be appropriate for them.

Talk food safety. RDs should counsel patients who test positive for PI-IBS on food safety; if these patients experience food poisoning again, the level of antibodies will increase and may lead to more severe IBS symptoms. Proper food handling and preparation as well as careful food selection while traveling are critical.

Look for the unnoticeable. Dietitians may want to assess for comorbid IBS when they encounter patients with IBD who have carefully followed dietary and pharmacological treatment protocols but are still experiencing symptoms, as it’s possible for IBD sufferers to be in remission clinically and experience symptoms due to undiagnosed IBS.21

Bottom Line
Should additional, large-scale studies provide further validation, the ibs-smart blood test will offer the promise of reducing time to diagnosis for patients with PI-IBS. This will improve quality of life for patients, decrease medical costs, and ease the economic burden on the entire health care system. However, the test shouldn’t be used as the sole diagnostic tool for IBS due to several important limitations.

— Diana Reid, MPH, RD, aka The Global Dietitian, provides nutrition counseling and consulting services in both the United States and Luxembourg and spends part of the year in each country. Reid specializes in gastrointestinal health and was trained at Monash University and King’s College London in implementing the low-FODMAP diet. She blogs on her website and writes regularly for FODMAP Everyday. Follow her on Facebook, Instagram, and Twitter @theglobalrd.

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