A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis
JRF Walters, AM Tasleem, OS Omer, WG Brydon… - Clinical …, 2009 - Elsevier
JRF Walters, AM Tasleem, OS Omer, WG Brydon, T Dew, CW Le Roux
Clinical Gastroenterology and Hepatology, 2009•ElsevierBACKGROUND & AIMS: Primary (idiopathic) bile acid malabsorption (BAM) is a common,
yet underrecognized, chronic diarrheal syndrome. Diagnosis is difficult without selenium
homocholic acid taurine testing. The diarrhea results from excess colonic bile acids, but the
pathogenesis is unclear. Fibroblast growth factor 19 (FGF19), produced in the ileum in
response to bile acid absorption, regulates hepatic bile acid synthesis. We proposed that
FGF19 is involved in bile acid diarrhea and measured its levels in patients with BAM …
yet underrecognized, chronic diarrheal syndrome. Diagnosis is difficult without selenium
homocholic acid taurine testing. The diarrhea results from excess colonic bile acids, but the
pathogenesis is unclear. Fibroblast growth factor 19 (FGF19), produced in the ileum in
response to bile acid absorption, regulates hepatic bile acid synthesis. We proposed that
FGF19 is involved in bile acid diarrhea and measured its levels in patients with BAM …
BACKGROUND & AIMS
Primary (idiopathic) bile acid malabsorption (BAM) is a common, yet underrecognized, chronic diarrheal syndrome. Diagnosis is difficult without selenium homocholic acid taurine testing. The diarrhea results from excess colonic bile acids, but the pathogenesis is unclear. Fibroblast growth factor 19 (FGF19), produced in the ileum in response to bile acid absorption, regulates hepatic bile acid synthesis. We proposed that FGF19 is involved in bile acid diarrhea and measured its levels in patients with BAM.
METHODS
Blood was collected from fasting patients with chronic diarrhea; BAM was diagnosed by selenium homocholic acid taurine testing. Serum FGF19 was measured by enzyme-linked immunosorbent assay (ELISA). Serum 7α-hydroxy-4-cholesten-3-one (C4) was determined using high-performance liquid chromatography (HPLC), to quantify bile acid synthesis. Data were compared between patients and subjects without diarrhea (controls). Samples were taken repeatedly after meals from several subjects.
RESULTS
The median C4 level was significantly higher in patients with primary BAM than in controls (51 vs 18 ng/mLl; P < .0001). The median FGF19 level was significantly lower in patients with BAM (120 vs 231 pg/mL; P < .0005). There was a significant inverse relationship between FGF19 and C4 levels (P < .0004). Low levels of FGF19 were also found in patients with postcholecystectomy and secondary bile acid diarrhea. Abnormal patterns of FGF19 levels were observed throughout the day in some patients with primary BAM.
CONCLUSIONS
Patients with BAM have reduced serum levels of FGF19; this finding might be useful in diagnosis. We propose a mechanism whereby impaired FGF19 feedback inhibition causes excessive bile acid synthesis that exceeds the normal capacity for ileal reabsorption, producing bile acid diarrhea.
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