Altered bile acid metabolism in childhood functional constipation: inactivation of secretory bile acids by sulfation in a subset of patients
Abstract
OBJECTIVE: An elevated concentration in the colon of the primary bile acid chenodeoxycholic acid (CDCA) or the secondary bile acid deoxycholic acid (DCA) is known to induce water secretion, causing diarrhea. We hypothesized that of the many fecal bile acids, only CDCA and DCA function as endogenous laxatives; therefore, a decrease in their proportion may be a cause of childhood functional constipation. To test this possibility, fecal bile acid composition was determined in children with functional constipation and in nonconstipated control children. PATIENTS AND METHODS: Fecal samples were obtained from 207 children, 103 with functional constipation and 104 with normal bowel habits. Bile acid classes were determined by use of electrospray ionization-single ion monitoring-mass spectrometry (ESI-SIM-MS), and individual bile acids were measured by gas chromatography (GC)-MS (GC-MS). The structure of individual sulfated bile acids was obtained by use of liquid chromatography (LC)-MS (LC-MS). RESULTS: By ESI-SIM-MS, the proportions of DCA did not differ in constipated children (n = 73) from that in control children (n = 92), but monosulfated dihydroxy bile acids were greater (P < 0.05). The difference was attributable to 6 patients in the constipated group whose major fecal bile acid by LC-MS was the 3-sulfate of CDCA. Sulfation of CDCA is known to abolish its secretory activity. By GC-MS, the bile acid profile was identical in the 2 groups. CONCLUSIONS: In most children with functional constipation, the fecal bile acid profile seems to be normal. There is a small subset of children, however, whose dominant fecal bile acid is the 3-sulfate of CDCA, indicating a novel disturbance in bile acid metabolism. Such sulfation abolishes the secretory activity of CDCA and may contribute to constipation.
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The gut microbiota may influence functional constipation through its impact on bile acid sulfation, in which colonic bacterial bile salt sulfatase may desulfate bile acids, empowering their effect to stimulate colonic secretion and transit and consequently improve colonic fluid transport.
“Another mechanism for the gut microbiota to influence FC is through its impact on BA sulfation, which abolishes the effect of the BAs on fluid transport [ 51 , 52 ]. BA sulfation likely occurred in hepatocytes, while colonic bacterial bile salt sulfatase may desulfate BA, empowering its effect to stimulate colonic secretion and transit, and consequently improve colonic fluid transport [ 53 ].”
From Role of gut microbiota in functional constipation (2021) · cites this paper as [51]
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- Authors
- Hofmann, A. F., Loening‐Baucke, V., Lavine, J. E., Hagey, L. R., Steinbach, J. H., Packard, C. A., Griffin, T. L., & Chatfield, D. A.
- Affiliations
- Division of Gastroenterology Department of Medicine USA
- Department of Pediatrics University of Iowa Iowa City USA
- University of California San Diego (US)
- San Diego State University (US)
- Corresponding author
- Hofmann, Alan F
- Hagey, Lee R
- Steinbach, Joseph H
- Venue
- Journal of Pediatric Gastroenterology and Nutrition
- Publisher
- Wiley
- Published
- 2008-11
- Volume
- 47
- Issue
- 5
- Pages
- 598-606
- ISSN
- 0277-2116 (ISSN-L)
- 1536-4801
- OpenAlex
- W2093776293
- Cited by
- 75
- References
- 52
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 9 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 4
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pediatric Gastroenterology and Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (64891)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- bile acid metabolism, chenodeoxycholic acid, deoxycholic acid, fecal bile acids
- MeSH terms
- Bile Acids and Salts, Chenodeoxycholic Acid, Child, Child, Preschool, Colon, Constipation, Defecation, Deoxycholic Acid, Feces, Female, Humans, Infant, Male, Gas Chromatography-Mass Spectrometry, Reference Values, Sulfates
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