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

Abstract

BackgroundEnvironmental 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 findingsWe 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/SignificanceIntestinal 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.

Association of faecal pH with childhood stunting: Results from a cross-sectional study

“…The burden of malnutrition is very high in children living in low-income and middle-income countries (LMICs) 1. Chronic malnutrition, which is manifested as linear growth failure or stunting,2 is the most common form of malnutrition across the globe, affecting about one-third of children in LMICs 3. Among these LMICs, countries from the southern Asia, specifically Bangladesh, India, Pakistan, Nepal and Bhutan, harbour a substantially high number of stunted children 4.…”

“…Among these LMICs, countries from the southern Asia, specifically Bangladesh, India, Pakistan, Nepal and Bhutan, harbour a substantially high number of stunted children 4. Stunted children suffer from reduced neurodevelopmental potential and poor cognitive function,2 thus fail to reach their full developmental potential,5 leading to substandard educational performance and economic productivity in the later phases of life 6. The aetiology of stunting is poorly understood4 and though poverty-associated food insecurity might play a vital role, the aetiology of this condition is far more complex 7.…”

A review of GI conditions critical to oral drug absorption in malnourished children

“…As the severity of malnutrition increases so do the changes in the intestinal epithelium as the abnormalities in marasmus were mild in comparison to children (aged 0-3 years) with kwashiorkor [76]. Atrophy of villi in malnutrition has also been reported [68][69][70].…”

Metabolic phenotyping of malnutrition during the first 1000 days of life

“…These have recently defined as “ HAZdrop ”, “COG-hit” and “ Met-syn” , respectively [ 70 ]. As a major hallmark of EED, metabolites associated with villus damage were investigated in hospitalized children with SAM from Zambia [ 71 ]. In this study, measures of villus health obtained from small intestinal biopsies were correlated with matched urinary metabolic phenotypes.…”