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Childhood growth and neurocognition are associated with distinct sets of metabolites.

Abstract：

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).

journal_name

EBioMedicine

journal_title

EBioMedicine

authors

Moreau GB,Ramakrishnan G,Cook HL,Fox TE,Nayak U,Ma JZ,Colgate ER,Kirkpatrick BD,Haque R,Petri WA Jr

doi

10.1016/j.ebiom.2019.05.043

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

597-606

issn

2352-3964

pii

S2352-3964(19)30351-2

journal_volume

44

pub_type

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