TY - JOUR
T1 - Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition
AU - Zhang, Ling
AU - Voskuijl, Wieger
AU - Mouzaki, Marialena
AU - Groen, Albert K.
AU - Alexander, Jennifer
AU - Bourdon, Celine
AU - Wang, Alice
AU - Versloot, Christian J.
AU - Di Giovanni, Valeria
AU - Wanders, Ronald J. A.
AU - Bandsma, Robert
PY - 2016/5/10
Y1 - 2016/5/10
N2 - ObjectiveSevere 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.DesignAn 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.ResultsOn 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.ConclusionSAM 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.
AB - ObjectiveSevere 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.DesignAn 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.ResultsOn 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.ConclusionSAM 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.
KW - FATTY LIVER-DISEASE
KW - MALNOURISHED CHILDREN
KW - MALABSORPTION
KW - KWASHIORKOR
KW - ABSORPTION
KW - 7-ALPHA-HYDROXY-4-CHOLESTEN-3-ONE
KW - ENTEROPATHY
KW - CHOLESTASIS
KW - ACTIVATION
KW - RECEPTORS
U2 - 10.1371/journal.pone.0155143
DO - 10.1371/journal.pone.0155143
M3 - Article
C2 - 27163928
VL - 11
JO - PLOS-One
JF - PLOS-One
SN - 1932-6203
IS - 5
M1 - e0155143
ER -