Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea
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...
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| Veröffentlicht in: | PloS one 2018-03, Vol.13 (3), p.e0192092-e0192092 |
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| creator | Farràs, Marta Chandwe, Kanta Mayneris-Perxachs, Jordi Amadi, Beatrice Louis-Auguste, John Besa, Ellen Zyambo, Kanekwa Guerrant, Richard Kelly, Paul Swann, Jonathan Richard |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0192092 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0192092</identifier><identifier>PMID: 29499047</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Anthropometry ; Bioindicators ; Biology and Life Sciences ; Biomarkers ; Cancer ; Child malnutrition ; Children ; Chronic illnesses ; Diarrhea ; Diarrhea - complications ; Diarrhea - pathology ; Digestive system ; Digestive tract ; Endoscopy ; Energy metabolism ; Excretion ; Female ; Gastroenterology ; Gastrointestinal Microbiome ; Gastrointestinal tract ; Growth Disorders - blood ; Growth Disorders - complications ; Growth Disorders - pathology ; Health ; Health aspects ; 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 microflora ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - microbiology ; Intestinal Mucosa - pathology ; Intestine ; Liver diseases ; Low income groups ; Magnetic permeability ; Magnetic resonance ; Male ; Malnutrition ; Medicine ; Medicine and Health Sciences ; Metabolism ; Metabolites ; Microbiota ; Microorganisms ; Mortality ; Muscles ; NMR ; Nuclear magnetic resonance ; Nutrition research ; Observations ; Parameters ; Pathogenesis ; Permeability ; Phenotype ; Phenotypes ; Physical Sciences ; Physiological aspects ; Properties ; Research and analysis methods ; Severe Acute Malnutrition - complications ; Severe Acute Malnutrition - pathology ; Spectroscopy ; Sucrose ; Sugar ; Surgery ; Translocation ; Tropical environments ; Undernutrition ; Villi ; Villus ; Zambia</subject><ispartof>PloS one, 2018-03, Vol.13 (3), p.e0192092-e0192092</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Farràs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Farràs et al 2018 Farràs et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6c9fe9c32c06249aaf071c8fd6ef099b8f5f03f97596526b7590e811bb0ef1783</citedby><cites>FETCH-LOGICAL-c692t-6c9fe9c32c06249aaf071c8fd6ef099b8f5f03f97596526b7590e811bb0ef1783</cites><orcidid>0000-0001-9776-3773</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834158/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834158/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29499047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Azman, Andrew S.</contributor><creatorcontrib>Farràs, Marta</creatorcontrib><creatorcontrib>Chandwe, Kanta</creatorcontrib><creatorcontrib>Mayneris-Perxachs, Jordi</creatorcontrib><creatorcontrib>Amadi, Beatrice</creatorcontrib><creatorcontrib>Louis-Auguste, John</creatorcontrib><creatorcontrib>Besa, Ellen</creatorcontrib><creatorcontrib>Zyambo, Kanekwa</creatorcontrib><creatorcontrib>Guerrant, Richard</creatorcontrib><creatorcontrib>Kelly, Paul</creatorcontrib><creatorcontrib>Swann, Jonathan Richard</creatorcontrib><title>Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Anthropometry</subject><subject>Bioindicators</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Child malnutrition</subject><subject>Children</subject><subject>Chronic illnesses</subject><subject>Diarrhea</subject><subject>Diarrhea - complications</subject><subject>Diarrhea - pathology</subject><subject>Digestive system</subject><subject>Digestive tract</subject><subject>Endoscopy</subject><subject>Energy metabolism</subject><subject>Excretion</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Gastrointestinal Microbiome</subject><subject>Gastrointestinal tract</subject><subject>Growth Disorders - blood</subject><subject>Growth Disorders - complications</subject><subject>Growth Disorders - pathology</subject><subject>Health</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant Nutrition Disorders - complications</subject><subject>Infant Nutrition Disorders - pathology</subject><subject>Insulin-Like Growth Factor Binding Protein 3 - blood</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Intestinal Diseases - complications</subject><subject>Intestinal Diseases - metabolism</subject><subject>Intestinal Diseases - pathology</subject><subject>Intestinal microflora</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Intestinal Mucosa - pathology</subject><subject>Intestine</subject><subject>Liver diseases</subject><subject>Low income groups</subject><subject>Magnetic permeability</subject><subject>Magnetic resonance</subject><subject>Male</subject><subject>Malnutrition</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Microbiota</subject><subject>Microorganisms</subject><subject>Mortality</subject><subject>Muscles</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Nutrition research</subject><subject>Observations</subject><subject>Parameters</subject><subject>Pathogenesis</subject><subject>Permeability</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Properties</subject><subject>Research and analysis methods</subject><subject>Severe Acute Malnutrition - complications</subject><subject>Severe Acute Malnutrition - pathology</subject><subject>Spectroscopy</subject><subject>Sucrose</subject><subject>Sugar</subject><subject>Surgery</subject><subject>Translocation</subject><subject>Tropical environments</subject><subject>Undernutrition</subject><subject>Villi</subject><subject>Villus</subject><subject>Zambia</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uL1DAUx4so7rr6DUQDgujDjEnbtM2LsAxeBhYWvD34EtL0ZJohk9QkHV2_hF_ZdGd2mZF9kD6kJL_zP_cse0rwnBQ1ebN2o7fCzAdnYY4JyzHL72WnhBX5rMpxcf_g_yR7FMIaY1o0VfUwO8lZyRgu69Psz6IXXsgIXv_WdoViD2gDUbTOaImGHqyLVwMgp5C2EULUySfaamPGgFoz2jhZaYu-i02rhUWy16bzYNFPHXsUYAsekJBjTLrC2DF6HbWzSNgODeCDDhFsRJ0W3vcgHmcPlDABnuzPs-zr-3dfFh9nF5cflovzi5msWB5nlWQKmCxyiau8ZEIoXBPZqK4ChRlrG0UVLhSrKatoXrXpxNAQ0rYYFKmb4ix7vtMdjAt8X8vAc4xZU9e4polY7ojOiTUfvN4If8Wd0Pz6wvkVFz5qaYA3tKi7EmPZ4aqkqRGMNqRqi66kTY0JSVpv997GdgOdTBl7YY5Ej1-s7vnKbTltipLQKdxXewHvfoypDXyjgwRjhAU3TnETXNQ5o1PcL_5B785uT61ESkBb5ZJfOYnyc5p06jK_dju_g0pfBxst0-Apne6PDF4fGSQmwq-4EmMIfPn50_-zl9-O2ZcHbJoTE_vgzDiNUjgGyx0ovQvBg7otMsF82pubavBpb_h-b5LZs8MG3RrdLErxFxFuFOo</recordid><startdate>20180302</startdate><enddate>20180302</enddate><creator>Farràs, Marta</creator><creator>Chandwe, Kanta</creator><creator>Mayneris-Perxachs, Jordi</creator><creator>Amadi, Beatrice</creator><creator>Louis-Auguste, John</creator><creator>Besa, Ellen</creator><creator>Zyambo, Kanekwa</creator><creator>Guerrant, Richard</creator><creator>Kelly, Paul</creator><creator>Swann, Jonathan Richard</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-9776-3773</orcidid></search><sort><creationdate>20180302</creationdate><title>Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea</title><author>Farràs, Marta ; Chandwe, Kanta ; Mayneris-Perxachs, Jordi ; Amadi, Beatrice ; Louis-Auguste, John ; Besa, Ellen ; Zyambo, Kanekwa ; Guerrant, Richard ; Kelly, Paul ; Swann, Jonathan Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6c9fe9c32c06249aaf071c8fd6ef099b8f5f03f97596526b7590e811bb0ef1783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Anthropometry</topic><topic>Bioindicators</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Child malnutrition</topic><topic>Children</topic><topic>Chronic illnesses</topic><topic>Diarrhea</topic><topic>Diarrhea - 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microbiology</topic><topic>Intestinal Mucosa - pathology</topic><topic>Intestine</topic><topic>Liver diseases</topic><topic>Low income groups</topic><topic>Magnetic permeability</topic><topic>Magnetic resonance</topic><topic>Male</topic><topic>Malnutrition</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Microbiota</topic><topic>Microorganisms</topic><topic>Mortality</topic><topic>Muscles</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Nutrition research</topic><topic>Observations</topic><topic>Parameters</topic><topic>Pathogenesis</topic><topic>Permeability</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Properties</topic><topic>Research and analysis methods</topic><topic>Severe Acute Malnutrition - complications</topic><topic>Severe Acute Malnutrition - pathology</topic><topic>Spectroscopy</topic><topic>Sucrose</topic><topic>Sugar</topic><topic>Surgery</topic><topic>Translocation</topic><topic>Tropical environments</topic><topic>Undernutrition</topic><topic>Villi</topic><topic>Villus</topic><topic>Zambia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Farràs, Marta</creatorcontrib><creatorcontrib>Chandwe, Kanta</creatorcontrib><creatorcontrib>Mayneris-Perxachs, Jordi</creatorcontrib><creatorcontrib>Amadi, Beatrice</creatorcontrib><creatorcontrib>Louis-Auguste, John</creatorcontrib><creatorcontrib>Besa, Ellen</creatorcontrib><creatorcontrib>Zyambo, Kanekwa</creatorcontrib><creatorcontrib>Guerrant, Richard</creatorcontrib><creatorcontrib>Kelly, Paul</creatorcontrib><creatorcontrib>Swann, Jonathan Richard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>Proquest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Farràs, Marta</au><au>Chandwe, Kanta</au><au>Mayneris-Perxachs, Jordi</au><au>Amadi, Beatrice</au><au>Louis-Auguste, John</au><au>Besa, Ellen</au><au>Zyambo, Kanekwa</au><au>Guerrant, Richard</au><au>Kelly, Paul</au><au>Swann, Jonathan Richard</au><au>Azman, Andrew S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-03-02</date><risdate>2018</risdate><volume>13</volume><issue>3</issue><spage>e0192092</spage><epage>e0192092</epage><pages>e0192092-e0192092</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29499047</pmid><doi>10.1371/journal.pone.0192092</doi><tpages>e0192092</tpages><orcidid>https://orcid.org/0000-0001-9776-3773</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-03, Vol.13 (3), p.e0192092-e0192092 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2009877075 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Anthropometry Bioindicators Biology and Life Sciences Biomarkers Cancer Child malnutrition Children Chronic illnesses Diarrhea Diarrhea - complications Diarrhea - pathology Digestive system Digestive tract Endoscopy Energy metabolism Excretion Female Gastroenterology Gastrointestinal Microbiome Gastrointestinal tract Growth Disorders - blood Growth Disorders - complications Growth Disorders - pathology Health Health aspects 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 microflora Intestinal Mucosa - metabolism Intestinal Mucosa - microbiology Intestinal Mucosa - pathology Intestine Liver diseases Low income groups Magnetic permeability Magnetic resonance Male Malnutrition Medicine Medicine and Health Sciences Metabolism Metabolites Microbiota Microorganisms Mortality Muscles NMR Nuclear magnetic resonance Nutrition research Observations Parameters Pathogenesis Permeability Phenotype Phenotypes Physical Sciences Physiological aspects Properties Research and analysis methods Severe Acute Malnutrition - complications Severe Acute Malnutrition - pathology Spectroscopy Sucrose Sugar Surgery Translocation Tropical environments Undernutrition Villi Villus Zambia |
| title | Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea |
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