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Published on: November 27, 2016
Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition
Ling Zhang1, Wieger Voskuijl2,3, Marialena Mouzaki4
1Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, Canada.
Insights
Severe acute malnutrition (SAM) in children is linked to higher serum bile acids, even with reduced synthesis. This suggests altered bile acid metabolism may contribute to liver disease in SAM patients.
Area of Science:
- Biochemistry
- Pediatric Nutrition
- Gastroenterology
Background:
- Severe acute malnutrition (SAM) is a critical factor in childhood mortality.
- SAM is frequently associated with hepatic steatosis (fatty liver disease).
- Bile acids play vital roles in digestion, energy regulation, and immunity.
Purpose of the Study:
- To investigate the association between SAM and clinically significant alterations in bile acid homeostasis.
- To understand how bile acid metabolism changes in children with SAM.
Main Methods:
- A discovery cohort (5 controls, 22 SAM patients) identified altered bile acid profiles.
- A follow-up cohort (40 SAM patients) was studied on admission and after stabilization.
- Bile acids, FGF19, and C4 were quantified in serum and feces; fecal calprotectin measured inflammation.
Main Results:
- Children with SAM exhibited significantly higher serum bile acids (primarily glycine-conjugates) compared to controls.
- Despite elevated serum levels, bile acid synthesis (indicated by C4) was reduced in SAM.
- Increased fecal secondary bile acids and decreased conjugated bile acids suggested enhanced bacterial conversion in SAM patients.
Conclusions:
- SAM is associated with elevated serum bile acid levels, paradoxical to reduced synthesis rates.
- Increased deconjugation and bacterial conversion of bile acids in SAM may contribute to liver pathology.
- Understanding these metabolic shifts is crucial for managing SAM and its complications.
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, 7α-hydroxy-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 μmol/L [8.6-47.7] compared to 1.9 μmol/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.
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