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1. Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea.

Author

Marta Farràs, Kanta Chandwe, Jordi Mayneris-Perxachs, Beatrice Amadi, John Louis-Auguste, Ellen Besa, Kanekwa Zyambo, Richard Guerrant, Paul Kelly, and Jonathan Richard Swann

Subjects
Medicine, Science
Abstract

Environmental enteric dysfunction (EED) is widespread throughout the tropics and in children is associated with stunting and other adverse health outcomes. One of the hallmarks of EED is villus damage. In children with severe acute malnutrition (SAM) the severity of enteropathy is greater and short term mortality is high, but the metabolic consequences of enteropathy are unknown. Here, we characterize the urinary metabolic alterations associated with villus health, classic enteropathy biomarkers and anthropometric measurements in severely malnourished children in Zambia.We analysed 20 hospitalised children with acute malnutrition aged 6 to 23 months in Zambia. Small intestinal biopsies were assessed histologically (n = 15), anthropometric and gut function measurements were collected and the metabolic phenotypes were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. Endoscopy could not be performed on community controls children. Growth parameters were inversely correlated with enteropathy biomarkers (p = 0.011) and parameters of villus health were inversely correlated with translocation and permeability biomarkers (p = 0.000 and p = 0.015). Shorter villus height was associated with reduced abundance of metabolites related to gut microbial metabolism, energy and muscle metabolism (p = 0.034). Villus blunting was also related to increased sucrose excretion (p = 0.013).Intestinal villus blunting is associated with several metabolic perturbations in hospitalized children with severe undernutrition. Such alterations include altered muscle metabolism, reinforcing the link between EED and growth faltering, and a disruption in the biochemical exchange between the gut microbiota and host. These findings extend our understanding on the downstream consequences of villus blunting and provide novel non-invasive biomarkers of enteropathy dysfunction. The major limitations of this study are the lack of comparative control group and gut microbiota characterization.

Published
2018
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2. Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea

Author

Paul Kelly, Jordi Mayneris-Perxachs, Jonathan R. Swann, John Louis-Auguste, Kanekwa Zyambo, Beatrice Amadi, Kanta Chandwe, Ellen Besa, Marta Farràs, Richard Guerrant, and Bill & Melinda Gates Foundation

Subjects
0301 basic medicine, Male, Sucrose, Physiology, lcsh:Medicine, Gut flora, Spectrum analysis techniques, Disaccharides, Biochemistry, Infant nutrition disorder, 0302 clinical medicine, Intestinal mucosa, Metabolites, Medicine and Health Sciences, Enteropathy, 030212 general & internal medicine, Insulin-Like Growth Factor I, Intestinal Mucosa, lcsh:Science, Growth Disorders, Multidisciplinary, biology, Organic Compounds, digestive, oral, and skin physiology, Infant Nutrition Disorders, Diarrhea, Chemistry, medicine.anatomical_structure, Phenotype, Physical Sciences, Female, medicine.symptom, Anatomy, Enteropathies, Research Article, General Science & Technology, Severe Acute Malnutrition, Carbohydrates, Excretion, Zambia, Gastroenterology and Hepatology, digestive system, 03 medical and health sciences, NMR spectroscopy, MD Multidisciplinary, medicine, Humans, Nutrition, business.industry, Intestinal villus, lcsh:R, Malnutrition, Organic Chemistry, Chemical Compounds, Infant, Correction, Biology and Life Sciences, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, Research and analysis methods, Gastrointestinal Tract, Intestinal Diseases, 030104 developmental biology, Insulin-Like Growth Factor Binding Protein 3, Metabolism, lcsh:Q, business, Physiological Processes, Digestive System, Biomarkers
Abstract

BACKGROUND: Environmental enteric dysfunction (EED) is widespread throughout the tropics and in children is associated with stunting and other adverse health outcomes. One of the hallmarks of EED is villus damage. In children with severe acute malnutrition (SAM) the severity of enteropathy is greater and short term mortality is high, but the metabolic consequences of enteropathy are unknown. Here, we characterize the urinary metabolic alterations associated with villus health, classic enteropathy biomarkers and anthropometric measurements in severely malnourished children in Zambia.METHODS/PRINCIPAL FINDINGS: We analysed 20 hospitalised children with acute malnutrition aged 6 to 23 months in Zambia. Small intestinal biopsies were assessed histologically (n = 15), anthropometric and gut function measurements were collected and the metabolic phenotypes were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. Endoscopy could not be performed on community controls children. Growth parameters were inversely correlated with enteropathy biomarkers (p = 0.011) and parameters of villus health were inversely correlated with translocation and permeability biomarkers (p = 0.000 and p = 0.015). Shorter villus height was associated with reduced abundance of metabolites related to gut microbial metabolism, energy and muscle metabolism (p = 0.034). Villus blunting was also related to increased sucrose excretion (p = 0.013).CONCLUSIONS/SIGNIFICANCE: Intestinal villus blunting is associated with several metabolic perturbations in hospitalized children with severe undernutrition. Such alterations include altered muscle metabolism, reinforcing the link between EED and growth faltering, and a disruption in the biochemical exchange between the gut microbiota and host. These findings extend our understanding on the downstream consequences of villus blunting and provide novel non-invasive biomarkers of enteropathy dysfunction. The major limitations of this study are the lack of comparative control group and gut microbiota characterization.

Published
2018

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