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Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil

Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinar... Full description

Journal Title: Guerrant R. L., A. M. Leite, R. Pinkerton, P. H. Q. S. Medeiros, P. A. Cavalcante, M. DeBoer, M. Kosek, et al. 2016. “Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil.” PLoS ONE 11 (9): e0158772. doi:10.1371/journal.pone.0158772. http://dx.doi.org/10.1371/journal.pone.0158772.
Main Author: Guerrant, Richard L.
Other Authors: Leite, Alvaro M. , Pinkerton, Relana , Medeiros, Pedro H. Q. S. , Cavalcante, Paloma A. , Deboer, Mark , Kosek, Margaret , Duggan, Christopher , Gewirtz, Andrew , Kagan, Jonathan C. , Gauthier, Anna E. , Swann, Jonathan , Mayneris-Perxachs, Jordi , Bolick, David T. , Maier, Elizabeth A. , Guedes, Marjorie M. , Moore, Sean R. , Petri, William A. , Havt, Alexandre , Lima, Ila F. , Prata, Mara De Moura Gondim , Michaleckyj, Josyf C. , Scharf, Rebecca J. , Sturgeon, Craig , Fasano, Alessio , Lima, Aldo A. M.
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0158772
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title: Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil
format: Article
creator:
  • Guerrant, Richard L.
  • Leite, Alvaro M.
  • Pinkerton, Relana
  • Medeiros, Pedro H. Q. S.
  • Cavalcante, Paloma A.
  • Deboer, Mark
  • Kosek, Margaret
  • Duggan, Christopher
  • Gewirtz, Andrew
  • Kagan, Jonathan C.
  • Gauthier, Anna E.
  • Swann, Jonathan
  • Mayneris-Perxachs, Jordi
  • Bolick, David T.
  • Maier, Elizabeth A.
  • Guedes, Marjorie M.
  • Moore, Sean R.
  • Petri, William A.
  • Havt, Alexandre
  • Lima, Ila F.
  • Prata, Mara De Moura Gondim
  • Michaleckyj, Josyf C.
  • Scharf, Rebecca J.
  • Sturgeon, Craig
  • Fasano, Alessio
  • Lima, Aldo A. M.
subjects:
  • Biology And Life Sciences
  • Biochemistry
  • Biomarkers
  • Anatomy
  • Digestive System
  • Gastrointestinal Tract
  • Medicine And Health Sciences
  • Immunology
  • Immune Response
  • Inflammation
  • Diagnostic Medicine
  • Signs And Symptoms
  • Pathology And Laboratory Medicine
  • Physical Sciences
  • Chemistry
  • Chemical Compounds
  • Organic Compounds
  • Amino Acids
  • Aromatic Amino Acids
  • Tryptophan
  • Organic Chemistry
  • Proteins
  • Gastroenterology And Hepatology
  • Enteropathies
  • People And Places
  • Population Groupings
  • Age Groups
  • Children
  • Families
  • Nutrition
  • Malnutrition
  • Social Sciences
  • Anthropology
  • Physical Anthropology
  • Anthropometry
ispartof: Guerrant, R. L., A. M. Leite, R. Pinkerton, P. H. Q. S. Medeiros, P. A. Cavalcante, M. DeBoer, M. Kosek, et al. 2016. “Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil.” PLoS ONE 11 (9): e0158772. doi:10.1371/journal.pone.0158772. http://dx.doi.org/10.1371/journal.pone.0158772.
description: Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6–26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.
language: eng
source:
identifier: ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0158772
fulltext: fulltext_linktorsrc
issn:
  • 1932-6203
  • 19326203
url: Link


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titleBiomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil
creatorGuerrant, Richard L. ; Leite, Alvaro M. ; Pinkerton, Relana ; Medeiros, Pedro H. Q. S. ; Cavalcante, Paloma A. ; Deboer, Mark ; Kosek, Margaret ; Duggan, Christopher ; Gewirtz, Andrew ; Kagan, Jonathan C. ; Gauthier, Anna E. ; Swann, Jonathan ; Mayneris-Perxachs, Jordi ; Bolick, David T. ; Maier, Elizabeth A. ; Guedes, Marjorie M. ; Moore, Sean R. ; Petri, William A. ; Havt, Alexandre ; Lima, Ila F. ; Prata, Mara De Moura Gondim ; Michaleckyj, Josyf C. ; Scharf, Rebecca J. ; Sturgeon, Craig ; Fasano, Alessio ; Lima, Aldo A. M.
ispartofGuerrant, R. L., A. M. Leite, R. Pinkerton, P. H. Q. S. Medeiros, P. A. Cavalcante, M. DeBoer, M. Kosek, et al. 2016. “Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil.” PLoS ONE 11 (9): e0158772. doi:10.1371/journal.pone.0158772. http://dx.doi.org/10.1371/journal.pone.0158772.
identifierISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0158772
subjectBiology And Life Sciences ; Biochemistry ; Biomarkers ; Anatomy ; Digestive System ; Gastrointestinal Tract ; Medicine And Health Sciences ; Immunology ; Immune Response ; Inflammation ; Diagnostic Medicine ; Signs And Symptoms ; Pathology And Laboratory Medicine ; Physical Sciences ; Chemistry ; Chemical Compounds ; Organic Compounds ; Amino Acids ; Aromatic Amino Acids ; Tryptophan ; Organic Chemistry ; Proteins ; Gastroenterology And Hepatology ; Enteropathies ; People And Places ; Population Groupings ; Age Groups ; Children ; Families ; Nutrition ; Malnutrition ; Social Sciences ; Anthropology ; Physical Anthropology ; Anthropometry
descriptionCritical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6–26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.
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22Scharf, Rebecca J.
23Sturgeon, Craig
24Fasano, Alessio
25Lima, Aldo A. M.
titleBiomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil
descriptionCritical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6–26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.
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1Biochemistry
2Biomarkers
3Anatomy
4Digestive System
5Gastrointestinal Tract
6Medicine and Health Sciences
7Immunology
8Immune Response
9Inflammation
10Diagnostic Medicine
11Signs and Symptoms
12Pathology and Laboratory Medicine
13Physical Sciences
14Chemistry
15Chemical Compounds
16Organic Compounds
17Amino Acids
18Aromatic Amino Acids
19Tryptophan
20Organic Chemistry
21Proteins
22Gastroenterology and Hepatology
23Enteropathies
24People and Places
25Population Groupings
26Age Groups
27Children
28Families
29Nutrition
30Malnutrition
31Social Sciences
32Anthropology
33Physical Anthropology
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titleBiomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil
authorGuerrant, Richard L. ; Leite, Alvaro M. ; Pinkerton, Relana ; Medeiros, Pedro H. Q. S. ; Cavalcante, Paloma A. ; Deboer, Mark ; Kosek, Margaret ; Duggan, Christopher ; Gewirtz, Andrew ; Kagan, Jonathan C. ; Gauthier, Anna E. ; Swann, Jonathan ; Mayneris-Perxachs, Jordi ; Bolick, David T. ; Maier, Elizabeth A. ; Guedes, Marjorie M. ; Moore, Sean R. ; Petri, William A. ; Havt, Alexandre ; Lima, Ila F. ; Prata, Mara De Moura Gondim ; Michaleckyj, Josyf C. ; Scharf, Rebecca J. ; Sturgeon, Craig ; Fasano, Alessio ; Lima, Aldo A. M.
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11Signs And Symptoms
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13Physical Sciences
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15Chemical Compounds
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20Organic Chemistry
21Proteins
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24People And Places
25Population Groupings
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31Social Sciences
32Anthropology
33Physical Anthropology
34Anthropometry
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abstractCritical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6–26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.
pubPublic Library of Science
doi10.1371/journal.pone.0158772
urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045163/pdf/
issue9
volume11
pagese0158772
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