Identifying BAD (bile acid diarrhea) in IBS-D

BC Beinvogl et al. JPGN 2021; 72: 859-865. Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls

Background: Up to ~30% of adults with IBS-D may have bile acid diarrhea (BAD); however, identification has been hampered by cumbersome testing. In the U.S., the most reliable test has been a 48-hr fecal bile acid (FBA) level of >2337 micromol/48 h. Alternatively, blood tests have been used:

  1. 7alpha-hydroxy-4-cholesten-3-one (C4)–a direct measure of BA production
  2. Fibroblast growth factor-19 (FGF-19)–an indirect measure of ileal BA resorption

This prospective cross-sectional study of adolescents (n=26 and 56 healthy controls) examined these blood tests and 48-h FBA . Key findings:

  • 20% of IBS-D patients had elevated C4 levels based on 90% of serum C4 in healthy controls (HC). Mean value in HC was 12 and mean value in IBS-D was 16; 90th% was 22 in HC.
  • 28% had decreased fasting serum FGF-19 based on 10% of HC. Mean value in HC was 128 pg/mL compared with 93 in IBS-D; 10th% was 45 in HC.
  • There was good correlation between C4 and 48-h FBA and there was an inverse relationship between serum C4 and FGF-19. Mean value for 48-h FBA in HC was 490 micromol/48 h compared with 824 in IBS-D; 90th% was 972 in HC.

The authors argue that a definitive diagnosis of BAD is beneficial compared to empiric use of bile acid sequestrants. They point to studies showing that treatment is more effective in those with known BAD, up to 75% response rate. In addition, the use of empiric treatment “has not been validated as a diagnostic test for BAD.” Furthermore, definitive diagnosis would help with adherence to long-term treatment and avoid drug interactions/side effects in those who are unlikely to respond to treatment.

My take: This study shows that C4 could help identify BAD in IBS-D in adolescents and is in agreement with studies in adults (Mayo Clinic labs does run this test: Mayo Clinic: 7AC4, Bile Acid Synthesis, Serum).

Related blog posts:

Below is a sign from the broadwalk in Hollywood, FL. Watch out if you are eating something!

Clearing Out My Desk

These articles have been sitting on my desk or my email and worth a quick mention:

“Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial” DE Freedberg et al. Gastroenterol 2015; 149: 883-85. In this study of 12 healthy volunteers over 12 weeks, the study’s major finding (according to associated commentary) “is the absence of any significant changes in microbial diversity with proton pump inhibitors.” However, there was “an increase in bacterial taxa associated with C difficile infection.”

“Quality of Life and Its Determinants in a Multicenter Cohort of Children with Alagille Syndrome” BM Kamath et al. J Pediatr 2015; 167: 390-6.  Quality of life is impaired in Alagille compared to healthy children and children with alpha-one antitrypsin; it is associated with growth failure which may be modifiable.

“Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis” DH Leung et al. J Pediatr 2015; 167: 862-68.  In this prospective study of children (n=719) from age 3-12 years, unsuspected cirrhosis was seen in 3.3% of patients and a heterogeneous liver echotexture was identified in 8.9%.

Case report of phlegmonous gastritis associated with ulcerative colitis (with good pictures): J Cordova, R Gokhale, B Kirschner. Gastroenterol 2015; 149: 867-69.

“High Prevalence of Idiopathic Bile Acid Diarrhea Among Patients with Diarrhea-Predominant Irritable Bowel Syndrome Based on Rome III Criteria” I Aziz et al. Clin Gastroenterol Hepatol 2015; 13: 1650-55.

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study” The Lancet. DOI: (Reference from Sana Syed)