Childhood growth and neurocognition are associated with distinct sets of metabolitesResearch in context
Background: Undernutrition is a serious global problem that contributes to increased child morbidity and mortality, impaired neurocognitive development, and decreased educational and economic attainment. Current interventions are only marginally effective, and identification of associated metabolic...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-06-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419303512 |
| _version_ | 1818250286096973824 |
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| author | G. Brett Moreau Girija Ramakrishnan Heather L. Cook Todd E. Fox Uma Nayak Jennie Z. Ma E. Ross Colgate Beth D. Kirkpatrick Rashidul Haque William A. Petri, Jr |
| author_facet | G. Brett Moreau Girija Ramakrishnan Heather L. Cook Todd E. Fox Uma Nayak Jennie Z. Ma E. Ross Colgate Beth D. Kirkpatrick Rashidul Haque William A. Petri, Jr |
| author_sort | G. Brett Moreau |
| collection | DOAJ |
| description | Background: Undernutrition is a serious global problem that contributes to increased child morbidity and mortality, impaired neurocognitive development, and decreased educational and economic attainment. Current interventions are only marginally effective, and identification of associated metabolic pathways can offer new strategies for intervention. Methods: Plasma samples were collected at 9 and 36 months from a subset of the PROVIDE child cohort (n = 130). Targeted metabolomics was performed on bile acids, acylcarnitines, amino acids, phosphatidylcholines, and sphingomyelins. Metabolic associations with linear growth and neurocognitive outcomes at four years were evaluated using correlation and penalized-linear regression analysis as well as conditional random forest modeling. Findings: Different metabolites were associated with growth and neurocognitive outcomes. Improved growth outcomes were associated with higher concentrations of hydroxy-sphingomyelin and essential amino acids and lower levels of acylcarnitines and bile acid conjugation. Neurocognitive scores were largely associated with phosphatidylcholine species and early metabolic indicators of inflammation. All metabolites identified explain ~45% of growth and neurocognitive variation. Interpretation: Growth outcomes were predominantly associated with metabolites measured early in life (9 months), many of which were biomarkers of insufficient diet, environmental enteric dysfunction, and microbiome disruption. Hydroxy-sphingomyelin was a significant predictor of improved growth. Neurocognitive outcome was predominantly associated with 36 month phosphatidylcholines and inflammatory metabolites, which may serve as important biomarkers of optimal neurodevelopment. The distinct sets of metabolites associated with growth and neurocognition suggest that intervention may require targeted approaches towards distinct metabolic pathways. Fund: Bill & Melinda Gates Foundation (OP1173478); National Institutes of Health (AI043596, CA044579). Keywords: Metabolomics, Stunting, Neurocognition, Childhood, Phosphatidylcholine, Sphingomyelin |
| first_indexed | 2024-12-12T15:49:58Z |
| format | Article |
| id | doaj.art-6f5457841cc543b9add3f7033bc871f5 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-12T15:49:58Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-6f5457841cc543b9add3f7033bc871f52022-12-22T00:19:40ZengElsevierEBioMedicine2352-39642019-06-0144597606Childhood growth and neurocognition are associated with distinct sets of metabolitesResearch in contextG. Brett Moreau0Girija Ramakrishnan1Heather L. Cook2Todd E. Fox3Uma Nayak4Jennie Z. Ma5E. Ross Colgate6Beth D. Kirkpatrick7Rashidul Haque8William A. Petri, Jr9Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USADepartment of Statistics, University of Virginia, Charlottesville, VA, USADepartment of Pharmacology, University of Virginia, Charlottesville, VA, USACenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USADepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, USAVaccine Testing Center, Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, USAVaccine Testing Center, Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, USAInternational Centre for Diarrheal Disease Research, Dhaka, BangladeshDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; Corresponding author at: University of Virginia, Department of Medicine, Division of Infectious Diseases, 345 Crispell Drive, Charlottesville, VA 22908, USA.Background: Undernutrition is a serious global problem that contributes to increased child morbidity and mortality, impaired neurocognitive development, and decreased educational and economic attainment. Current interventions are only marginally effective, and identification of associated metabolic pathways can offer new strategies for intervention. Methods: Plasma samples were collected at 9 and 36 months from a subset of the PROVIDE child cohort (n = 130). Targeted metabolomics was performed on bile acids, acylcarnitines, amino acids, phosphatidylcholines, and sphingomyelins. Metabolic associations with linear growth and neurocognitive outcomes at four years were evaluated using correlation and penalized-linear regression analysis as well as conditional random forest modeling. Findings: Different metabolites were associated with growth and neurocognitive outcomes. Improved growth outcomes were associated with higher concentrations of hydroxy-sphingomyelin and essential amino acids and lower levels of acylcarnitines and bile acid conjugation. Neurocognitive scores were largely associated with phosphatidylcholine species and early metabolic indicators of inflammation. All metabolites identified explain ~45% of growth and neurocognitive variation. Interpretation: Growth outcomes were predominantly associated with metabolites measured early in life (9 months), many of which were biomarkers of insufficient diet, environmental enteric dysfunction, and microbiome disruption. Hydroxy-sphingomyelin was a significant predictor of improved growth. Neurocognitive outcome was predominantly associated with 36 month phosphatidylcholines and inflammatory metabolites, which may serve as important biomarkers of optimal neurodevelopment. The distinct sets of metabolites associated with growth and neurocognition suggest that intervention may require targeted approaches towards distinct metabolic pathways. Fund: Bill & Melinda Gates Foundation (OP1173478); National Institutes of Health (AI043596, CA044579). Keywords: Metabolomics, Stunting, Neurocognition, Childhood, Phosphatidylcholine, Sphingomyelinhttp://www.sciencedirect.com/science/article/pii/S2352396419303512 |
| spellingShingle | G. Brett Moreau Girija Ramakrishnan Heather L. Cook Todd E. Fox Uma Nayak Jennie Z. Ma E. Ross Colgate Beth D. Kirkpatrick Rashidul Haque William A. Petri, Jr Childhood growth and neurocognition are associated with distinct sets of metabolitesResearch in context EBioMedicine |
| title | Childhood growth and neurocognition are associated with distinct sets of metabolitesResearch in context |
| title_full | Childhood growth and neurocognition are associated with distinct sets of metabolitesResearch in context |
| title_fullStr | Childhood growth and neurocognition are associated with distinct sets of metabolitesResearch in context |
| title_full_unstemmed | Childhood growth and neurocognition are associated with distinct sets of metabolitesResearch in context |
| title_short | Childhood growth and neurocognition are associated with distinct sets of metabolitesResearch in context |
| title_sort | childhood growth and neurocognition are associated with distinct sets of metabolitesresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419303512 |
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