Inflammatory biomarkers in newly diagnosed primary care Irritable Bowel Syndrome: a subanalysis of the DOMINO Randomized Trial

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 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).