Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls

Abstract

Supplemental Digital Content is available in the text ABSTRACT Objectives: Excessive fecal bile acids in adults have been associated with diarrhea-predominant irritable bowel syndrome (IBS-D), but their role in pediatric IBS-D is unknown. Serum markers including 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor-19 (FGF-19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48-hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF–19 and 48FBA in a pediatric population, to compare measurements in IBS-D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS-D. Methods: Using a cross-sectional design, 26 patients with IBS-D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF-19 and 48FBA were obtained. Participants completed a 7-day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations. Results: Mean age was 14.7\u200a±\u200a2.5\u200ayears (42.3% female) in IBS-D and 12.6\u200a±\u200a2.4\u200ayears (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r\u200a=\u200a0.48, P\u200a<\u200a0.05) and an inverse association with FGF-19 (r\u200a=\u200a–0.43, P\u200a<\u200a0.05). No significant differences were noted in C4 (P\u200a=\u200a0.32), FGF-19 (P\u200a=\u200a0.1), or 48FBA (P\u200a=\u200a0.5) between IBS-D and HC groups; however, 20% of IBS-D patients had elevated C4 and 28% had low FGF-19 values. Fecal primary BA was significantly correlated with stool frequency (r\u200a=\u200a0.45, P\u200a<\u200a0.002). Conclusions: Correlations of C4 with 48FBA and FGF-19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS-D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS-D.