A study on the utility of inflammatory biomarkers in primary care irritable bowel syndrome: a sub analysis of the DOMINO randomized trial

Abstract

Background: The role of low-grade-inflammation in Irritable Bowel Syndrome (IBS) a common disorder of gut-brain interaction is unclear. Association with symptom severity, as well as effects of first line treatments are understudied. In a large cohort of primary care IBS patients (DOMINO trial), a FODMAP-lowering diet application was superior in improving symptoms compared to standard medical therapy (otilonium bromide, OB). We investigated the level of pro-inflammatory markers in this IBS cohort and its changes by the DOMINO application and OB. Methods: Inflammatory markers fecal calprotectin (FC), secretory IgA (sIgA), beta-defensin 2 (HBD-2), fecal elastase (Fel-1), and C-reactive protein (CRP) were analyzed at baseline and after 8-week of treatment (diet or medication). In addition, patients filled out questionnaires to score IBS criteria (Rome IV), IBS subtypes, and symptom severity (IBS-SSS). We used Mann-Whitney-U test, Wilcoxon test, Spearman correlation, Kruskal Wallis test and Chi-square analysis to analyze our data. Results: In the DOMINO trial, stool and blood samples of 445 patients were collected before and after treatment. At baseline, respectively 9, 19, 15, 20, 2% of the patients showed abnormal levels of CRP, FC, sIgA, HBD-2, and Fel-1 compared to standard thresholds. However, these markers did not correlate with IBS-SSS. In addition, CRP was significantly lower in IBS-C patients compared to other IBS subtypes. After a 8-week treatment with a FODMAP lowering diet application, both HBD-2 and FC were significantly decreased, while only HBD-2 was decreased with OB. Conclusion: Inflammatory markers (FC, CRP, sIgA, HBD-2, Fel-1) were not correlated with symptom severity or predictive of treatment response to a FODMAP diet or OB treatment in a large primary care IBS cohort. All markers decreased after 8-week treatment, with significant differences for HBD-2 and FC. The anti-inflammatory effect of both treatments needs to be further investigated. Trial registration: The trial was registered with ClinicalTrials.gov (NCT04270487, registered on 2020-05-04).