Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition

Ling Zhang, Wieger Voskuijl, Marialena Mouzaki, Albert K. Groen, Jennifer Alexander, Celine Bourdon, Alice Wang, Christian J. Versloot, Valeria Di Giovanni, Ronald J. A. Wanders, Robert Bandsma*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Objective

Severe acute malnutrition (SAM) is a major cause of mortality in children under 5 years and is associated with hepatic steatosis. Bile acids are synthesized in the liver and participate in dietary fat digestion, regulation of energy expenditure, and immune responses. The aim of this work was to investigate whether SAM is associated with clinically relevant changes in bile acid homeostasis.

Design

An initial discovery cohort with 5 healthy controls and 22 SAM-patients was used to identify altered bile acid homeostasis. A follow up cohort of 40 SAM-patients were then studied on admission and 3 days after clinical stabilization to assess recovery in bile acid metabolism. Recruited children were 6-60 months old and admitted for SAM in Malawi. Clinical characteristics, feces and blood were collected on admission and prior to discharge. Bile acids, 7ahydroxy-4-cholesten-3-one (C4) and FGF-19 were quantified.

Results

On admission, total serum bile acids were higher in children with SAM than in healthy controls and glycine-conjugates accounted for most of this accumulation with median and interquartile range (IQR) of 24.6 mu mol/L [8.6-47.7] compared to 1.9 mu mol/L [1.7-3.3] (p = 0.01) in controls. Total serum bile acid concentrations did not decrease prior to discharge. On admission, fecal conjugated bile acids were lower and secondary bile acids higher at admission compared to pre-discharge, suggesting increased bacterial conversion. FGF19 (Fibroblast growth factor 19), a marker of intestinal bile acid signaling, was higher on admission and was associated with decreased C4 concentrations as a marker of bile acid synthesis. Upon recovery, fecal calprotectin, a marker of intestinal inflammation, was lower.

Conclusion

SAM is associated with increased serum bile acid levels despite reduced synthesis rates. In SAM, there tends to be increased deconjugation of bile acids and conversion from primary to secondary bile acids, which may contribute to the development of liver disease.

Original languageEnglish
Article numbere0155143
Number of pages13
JournalPLoS ONE
Volume11
Issue number5
DOIs
Publication statusPublished - 10-May-2016

Keywords

  • FATTY LIVER-DISEASE
  • MALNOURISHED CHILDREN
  • MALABSORPTION
  • KWASHIORKOR
  • ABSORPTION
  • 7-ALPHA-HYDROXY-4-CHOLESTEN-3-ONE
  • ENTEROPATHY
  • CHOLESTASIS
  • ACTIVATION
  • RECEPTORS

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