Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea
Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea
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.
Diarrhea/complications, Female, Gastrointestinal Microbiome, Growth Disorders/blood, Humans, Infant, Infant Nutrition Disorders/complications, Insulin-Like Growth Factor Binding Protein 3/blood, Insulin-Like Growth Factor I/metabolism, Intestinal Diseases/complications, Intestinal Mucosa/metabolism, Male, Phenotype, Severe Acute Malnutrition/complications, Zambia
1-13
Farràs, Marta
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Chandwe, Kanta
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Mayneris-Perxachs, Jordi
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Amadi, Beatrice
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Louis-Auguste, John
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Besa, Ellen
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Zyambo, Kanekwa
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Guerrant, Richard
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Kelly, Paul
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Swann, Jonathan R.
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2 March 2018
Farràs, Marta
7abc4c88-e676-4a3b-a7e1-b2296de3c2b1
Chandwe, Kanta
d25f46b3-075a-4212-855e-85f1839f6996
Mayneris-Perxachs, Jordi
921cd6b1-1c40-4cb6-9d70-9d3c4f479a78
Amadi, Beatrice
15c15b90-ffc1-423a-b7fb-a562171b437b
Louis-Auguste, John
911ff61c-960f-4432-a28f-d72eab12bd11
Besa, Ellen
e8c57533-2585-4133-bc6f-3f7978ba84cd
Zyambo, Kanekwa
911d093a-cd47-4fe0-807e-29fde79cc73f
Guerrant, Richard
b8c9324a-fd9b-401e-b994-105406ee8fbd
Kelly, Paul
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Swann, Jonathan R.
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Farràs, Marta, Chandwe, Kanta, Mayneris-Perxachs, Jordi, Amadi, Beatrice, Louis-Auguste, John, Besa, Ellen, Zyambo, Kanekwa, Guerrant, Richard, Kelly, Paul and Swann, Jonathan R.
(2018)
Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea.
PLoS ONE, 13 (3), , [e0192092].
(doi:10.1371/journal.pone.0192092).
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.
Text
journal.pone.0192092
- Version of Record
More information
Accepted/In Press date: 16 January 2018
Published date: 2 March 2018
Keywords:
Diarrhea/complications, Female, Gastrointestinal Microbiome, Growth Disorders/blood, Humans, Infant, Infant Nutrition Disorders/complications, Insulin-Like Growth Factor Binding Protein 3/blood, Insulin-Like Growth Factor I/metabolism, Intestinal Diseases/complications, Intestinal Mucosa/metabolism, Male, Phenotype, Severe Acute Malnutrition/complications, Zambia
Identifiers
Local EPrints ID: 440756
URI: http://eprints.soton.ac.uk/id/eprint/440756
ISSN: 1932-6203
PURE UUID: 21ce4490-24fd-4300-afb3-d53838937277
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Date deposited: 15 May 2020 16:32
Last modified: 17 Mar 2024 04:00
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Contributors
Author:
Marta Farràs
Author:
Kanta Chandwe
Author:
Jordi Mayneris-Perxachs
Author:
Beatrice Amadi
Author:
John Louis-Auguste
Author:
Ellen Besa
Author:
Kanekwa Zyambo
Author:
Richard Guerrant
Author:
Paul Kelly
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