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

PLoS One. 2018 Mar 2;13(3):e0192092. doi: 10.1371/journal.pone.0192092. eCollection 2018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diarrhea / complications
  • Diarrhea / pathology*
  • Female
  • Gastrointestinal Microbiome
  • Growth Disorders / blood
  • Growth Disorders / complications
  • Growth Disorders / pathology
  • Humans
  • Infant
  • Infant Nutrition Disorders / complications
  • Infant Nutrition Disorders / pathology*
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / metabolism
  • Intestinal Diseases / complications
  • Intestinal Diseases / metabolism
  • Intestinal Diseases / pathology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology*
  • Male
  • Phenotype
  • Severe Acute Malnutrition / complications
  • Severe Acute Malnutrition / pathology*
  • Zambia

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I

Grants and funding

CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III, Madrid, Spain. M.F. received a short-term stay fellowship from the CIBEROBN to work in this project. http://www.ciberobn.es/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.