Review article: biomarkers and personalised therapy in functional lower gastrointestinal disorders

Abstract

SUMMARY Background Treatment of IBS and lower functional gastrointestinal disorders is still based predominantly on symptoms; biomarkers that reflect the mechanism or pathophysiology have been identified. Given the diverse mechanisms that result in the same clinical phenotype of IBS, it is hypothesized that identification of biomarkers may lead to individualization of medical therapy. Aim To review the biomarkers that have been appraised in IBS. Methods A single author reviewed the published literature on biomarkers appraised in IBS. Results The current literature suggests that these biomarkers are insufficiently sensitive or specific to differentiate IBS from health or from other diseases causing similar symptoms, such as celiac disease or inflammatory bowel disease. Most of the proposed biomarkers are not actionable, that is, they do not lead to an efficacious therapy based on the biological inference of the biomarker itself. However, among proposed biomarkers in IBS, some are actionable, as they specifically reflect a quantitative difference in a mediator of dysfunction or result in a quantifiable disturbance of function that can be specifically treated. Such biomarkers may potentially identify relevant subgroups that respond to specific therapy. The most promising actionable biomarkers are measurement of colonic transit (leading to treatments that reverse the abnormal transit) and measurements of bile acid diarrhea to identify responders to bile acid sequestrants. Conclusions Therefore, although biomarkers are not ready for prime time as diagnostic tests in IBS, some biomarkers could identify subgroups of patients with IBS for inclusion in clinical trials that target specific dysfunctions. Such an approach may enhance treatment efficacy, and may ultimately help reduce costs in drug development and in the management of patients in clinical practice.

Enhancing Diagnostic Performance of Symptom-Based Criteria for Irritable Bowel Syndrome by Additional History and Limited Diagnostic Evaluation

“…Thus, the recently validated additional measurements of colonic transit or of bile acid metabolism still provide the best biomarkers to individualize therapy in subsets of IBS patients. 18,42 Finally, the approaches suggested by our findings may not completely change physician behavior, due to uncertainty or fear of a missed organic diagnosis, which is reflected by the fact that significantly more patients who met the Rome III criteria for IBS were referred for colonoscopy in this study. However, further proof of the validity of this approach in prospective cohorts will enhance the confidence with which physicians can make a positive diagnosis of IBS, which was the intent of the original symptom-based criteria proposed by Manning et al 13 In summary, the performance of the Rome III criteria in diagnosing IBS was similar to that observed in a previous validation study from a cohort in Canada.…”

Bile and fat excretion are biomarkers of clinically significant diarrhoea and constipation in irritable bowel syndrome

“…When added to IBS biomarker serological panels, psychological biomarkers enhanced the ability of the panels to differentiate IBS cases from healthy volunteers, but did not improve the discrimination between the different subtypes of IBS . More actionable biomarkers are measurements of colonic transit and bile acid excretion; in a prospective study of 120 patients with IBS, approximately 30% had abnormal colonic transit . Excretion of total and primary faecal bile acids may alter colonic function, increasing colonic motility and secretion in those with diarrhoea; and decreased total and primary faecal bile acids may result in constipation .…”

2015 James W. Freston Single Topic Conference: A Renaissance in the Understanding and Management of Irritable Bowel Syndrome

“…Current candidate biomarkers are shown in Table 1. 19–21 Some are already actionable (eg transit, BAs, serotonin). Future research will address microbial diversity and interactions with the host genome to better understand the pathobiology of IBS and lead to more targeted therapeutic approaches.…”