Related Experiment Video
Updated: Oct 15, 2025
Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
Published on: November 27, 2016
Bile Acid Profiling Reveals Distinct Signatures in Undernourished Children with Environmental Enteric Dysfunction
Xueheng Zhao1, Kenneth D R Setchell1,2, Rong Huang1
1Division of Pathology & Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Insights
Environmental enteric dysfunction (EED) in infants is linked to growth faltering. Bile acid metabolism dysregulation is associated with EED severity and growth issues, suggesting a potential therapeutic target.
Area of Science:
- Pediatric gastroenterology
- Metabolomics
- Nutritional science
Background:
- Environmental enteric dysfunction (EED) is a condition affecting impoverished children, causing intestinal inflammation and malabsorption.
- EED is strongly associated with early childhood growth faltering worldwide.
- The liver-gut axis plays a crucial role in nutrient absorption and overall health.
Purpose of the Study:
- To identify biomarkers in bile acid metabolism linked to inflammation and EED histology.
- To investigate bile acid profiles as predictors of growth outcomes in undernourished infants.
- To explore the role of the liver-gut axis in EED and childhood undernutrition.
Main Methods:
- A longitudinal study of undernourished Pakistani infants (n=365) and well-nourished controls (n=51) up to 24 months of age.
- Serum bile acid (sBA) profiles were measured using tandem mass spectrometry.
- Bile acid composition was analyzed in paired plasma and duodenal aspirates from a subset of children (n=63) undergoing endoscopy, correlating with EED histology and growth outcomes.
Main Results:
- Over 70% of undernourished infants exhibited elevated sBA concentrations, indicating subclinical cholestasis.
- Serum glycocholic acid (GCA) levels correlated with linear growth faltering (HAZ) and inflammation biomarkers.
- GCA proportion positively correlated with EED severity in both plasma and duodenal samples, with low secondary bile acid proportions observed.
Conclusions:
- Dysregulated bile acid metabolism is significantly associated with growth faltering and EED severity in undernourished children.
- Restoring bile acid homeostasis in the intestine presents a potential novel therapeutic strategy for undernutrition in EED.
- This research highlights the importance of the liver-gut axis in pediatric undernutrition and EED.
Background:
Intestinal inflammation and malabsorption in environmental enteric dysfunction (EED) are associated with early childhood growth faltering in impoverished settings worldwide.
Objectives:
The goal of this study was to identify candidate biomarkers associated with inflammation, EED histology, and as predictors of later growth outcomes by focusing on the liver-gut axis by investigating the bile acid metabolome.
Methods:
Undernourished rural Pakistani infants (n = 365) with weight-for-height Z score (WHZ) < -2 were followed up to the age of 24 mo and monitored for growth, infections, and EED. Well-nourished local children (n = 51) were controls, based on consistent WHZ > 0 and height-for-age Z score (HAZ) > -1 on 2 consecutive visits at 3 and 6 mo. Serum bile acid (sBA) profiles were measured by tandem MS at the ages of 3-6 and 9 mo and before nutritional intervention. Biopsies and duodenal aspirates were obtained following upper gastrointestinal endoscopy from a subset of children (n = 63) that responded poorly to nutritional intervention. BA composition in paired plasma and duodenal aspirates was compared based on the severity of EED histopathological scores and correlated to clinical and growth outcomes.
Results:
Remarkably, >70% of undernourished Pakistani infants displayed elevated sBA concentrations consistent with subclinical cholestasis. Serum glycocholic acid (GCA) correlated with linear growth faltering (HAZ, r = -0.252 and -0.295 at the age of 3-6 and 9 mo, respectively, P <0.001) and biomarkers of inflammation. The proportion of GCA positively correlated with EED severity for both plasma (rs = 0.324 P = 0.02) and duodenal aspirates (rs = 0.307 P = 0.06) in children with refractory wasting that underwent endoscopy, and the proportion of secondary BA was low in both undernourished and EED children.
Conclusions:
Dysregulated bile acid metabolism is associated with growth faltering and EED severity in undernourished children. Restoration of intestinal BA homeostasis may offer a novel therapeutic target for undernutrition in children with EED. This trial was registered at clinicaltrials.gov as NCT03588013.
More Related Videos
Related Concept Videos
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test