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

J Pediatr Gastroenterol Nutr. 2021 Jun 1;72(6):859-865.doi: 10.1097/MPG.0000000000003067.

Beate C Beinvogl 1, Mhd Louai Manini 2, Michael Camilleri 3, Leslie J Donato 4, William Scott Harmsen 5, Imad Absah 2, Elizabeth Burch 1, Neil L Schechter 6, Samuel Nurko 1


Author information

  • 1Center for Motility and Functional Gastrointestinal Disorders, Boston Children's Hospital, Boston, MA.
  • 2Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
  • 3Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic.
  • 4Department of Laboratory Medicine and Pathology, Mayo Clinic.
  • 5Harmsen, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
  • 6Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA.


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 ± 2.5 years (42.3% female) in IBS-D and 12.6 ± 2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF-19 (r = -0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF-19 (P = 0.1), or 48FBA (P = 0.5) 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 = 0.45, P < 0.002).

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.

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