Original article—alimentary tractA New Mechanism for Bile Acid Diarrhea: Defective Feedback Inhibition of Bile Acid Biosynthesis
Section snippets
Subjects
Patients with chronic diarrhea were identified in gastroenterology outpatient clinics and gave informed consent. The study was approved by the local Institutional Review Board, the Hammersmith, Queen Charlotte's & Chelsea Hospital's Research Ethics Committee. All 17 patients had troublesome watery diarrhea with more than 3 stools per day for more than 3 months. Other causes of diarrhea including Crohn's disease, celiac disease, lactose intolerance, and short bowel syndrome had been excluded.
Results
The details of the patient group and the control subects are shown in Table 1. As expected, there was a highly significant difference in bowel frequency. Fasting serum C4 values were significantly higher in the patient group than in control subjects (median 51 vs 18 ng/mL; P < .0001, Mann–Whitney test) (Figure 1A).
FGF19 was detected in the serum of all the patients and control subjects, with fasting values ranging from 16–655 pg/mL. Fasting serum FGF19 values were significantly lower (P =
Discussion
This is the first study to our knowledge where serum FGF19 has been investigated in patients with bile acid malabsorption. We found reduced levels of FGF19 in patients, associated with increased C4, indicating increased bile acid synthesis. These changes were present in the patients irrespective of whether their symptoms were associated with previous bowel resection or cholecystectomy, or whether they appeared to have primary BAM.
In our patients with primary BAM, serum bile acids were higher
Acknowledgments
The authors are grateful to their colleagues for referring patients. They acknowledge the help of Dr John Meek for serum bile acid assays, and Prof K. D. Bardhan and Dr H. J. N. Andreyev for fruitful discussions.
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Conflicts of interest The authors disclose no conflicts.
Funding Parts of this study were funded by a project grant from the Wellcome Trust. The authors are grateful for support from the NIHR Biomedical Research Centre funding scheme and use of the facilities of the Sir John McMichael Centre.
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