Clinically Useful Biomarkers for Irritable Bowel Syndrome?

A selected summary (Gastroenterol 2016; 150: 277-79) provides good insight into the subject of irritable bowel syndrome (IBS) biomarkers.  This summary focuses on a study by Pimental M et al (PLoS One 2015; 10: e0126438).

“In this study, the authors validated 2 serum biomarkers, antibodies (Abs) to cytolethal distending toxin (CdtB) and vinculin, primarily focused on differentiating diarrhea-predominant IBS (IBS-D) from IBD. CdtB is a bacterial toxin commonly produced by Campylobacter jejuni, as well as Escherichia coli, Salmonella, and Shigella…presence of Cdtb seems to be positively associated with the likelihood of developing a postinfectious IBS pehnotype…Vinculin is a host cell adhesion protein, with which anti-CdtB Abs are known to cross-react.”

The study recruited 2681 participants (18-65 years) from 180 centers; most (n=2375) had Rome III IBS-D.

Key findings:

  • Anti-CdtB levels were higher in IBS-D 2.53 (± 0.69) compared with Crohn’s disease 1.72 (± 0.81), ulcerative colitis 1.54 (± 0.68), celiac disease 2.23 (± 0.70), and healthy subjects 1.81 (± 0.73)
  • Anti-vinculin Abs were higher in IBS-D as well: 1.34 (± 0.85) compared with Crohn’s disease 1.05 (± 0.91),ulcerative colitis 0.96 (± 0.77), celiac disease 1.07 (± 0.98), and healthy subjects 0.81 (± 0.59)

“Using a cutoff point of >2.80 for anti-CdtB Abs, the sensitivity was 43.7%, specificity was 91.6%.”  The positive likelihood ratio (LR) was 5.2 with this cutoff.  For vinculin, a cutoff of >1.68, resulted in a sensitivity of 32.6%, specificity of 83.8%, and a positive LR of 2.0.

For comparison, the commentary notes that the Rome III criteria in one study had a sensitivity of 68.8%, specificity of 79.5%, and positive LR of 3.35.

“The current study is important for 2 reasons.  First, that these 2 Abs were able to differentiate IBS-D from IBD and healthy controls, with a reasonable degree of accuracy, suggests that a substantial proportion of individuals with IBS may have an overt or subclinical postinfectious trigger, resulting in intestinal microbial disturbances…Second, the ability of these tests, if positive, to rule in IBS-D and rule out IBD is encouraging.”


  • This study may not be representative of a typical primary care population with IBS
  • And,”as a rule of thumb, positive LRs of >10 are very useful in ruling in a disease…the complex, and likely multifactorial etiology of IBS may mean that a single biomarker that can diagnose IBS with the accuracy required for a test to be clinically useful is not possible.”

My take: I would like to see pediatric studies, perhaps this would help determine if a postinfectious mechanism is more common in children and adolescents.

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