Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi

Abstract

Stunting affects ∼25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood. The purpose of this study was to identify altered metabolic pathways associated with child stunting. We measured 677 serum metabolites using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12-59 mo, of whom 62% were stunted. A low height-for-age score (HAZ) was associated with lower serum concentrations of) ω-3 (n-3) and ω-6 (n-6) polyunsaturated fatty acids (PUFAs), ) sulfated neurosteroids, which play a role in brain development,) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and ) γ-glutamyl amino acids, which represent an altered γ-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure. This metabolomics study shows a cross-sectional association between stunting and low serum ω-3 and ω-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for β-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.

Prevalence and Correlates of Undernutrition in Young Children Living in Urban Slums of Mumbai, India: A Cross Sectional Study

“…The data presented here suggests that the effectiveness as well as reach of nutritional supplement programs such as Integrated Child Development Services may need to be reexamined particularly in urban slums among children in their second year of life. Other correlates of undernutrition in children suggested by other studies, such as circulating metabolites (90, 91) the gut microbiome (92–94), blood micronutrient concentrations (95), and immune function (96) require further exploration.…”

Pathophysiology of environmental enteric dysfunction and its impact on oral vaccine efficacy

“…30,31 In Malawian children with stunting, amino acids were found to be generally low 32 and ω-3 and ω-6 polyunsaturated fatty acids were also reduced in recent metabolomic studies. 33 Increasing data suggest that the microbiota constitutes a critical influence on the development of the gut and its mucosal immune system. Evidence from Malawi implicates dysbiosis (a flora altered in composition and usually reduced in complexity) in EED, 34,35 though whether dysbiosis initiates EE or merely perpetuates it is an unresolved question.…”

DHEAS and Human Development: An Evolutionary Perspective

“…However, IGF-1 is most directly associated with protein metabolism, including cell proliferation and differentiation (72) as well as protein synthesis (92). At an organismal level, variation in circulating IGF-1 levels has been related to differences in protein consumption across the life cycle, including during infancy (94), childhood (59), and adulthood (48,49). In fact, early protein consumption may lead to programing of the IGF-1 axis that becomes apparent during adolescence (95).…”

“…In the first section, I lay out a series of steps potentially linking intake of animal protein to brain development. These start with the consumption of animal protein which has been associated with higher IGF-1 levels in adults (48,49) and children (59). IGF-1 also has been implicated in the development of zona reticularis (52), suggesting that higher IGF-1 titers could promote a thicker zona reticularis and increased DHEAS production.…”