Effects of Early Nutrition on the Infant Metabolome

Hellmuth, Christian; Uhl, Olaf; Kirchberg, Franca F.; Grote, Veit; Weber, Martina; Rzehak, Peter; Carlier, Clotilde; Ferré, Natàlia; Verduci, Elvira; Gruszfeld, Dariusz; Socha, Piotr; Koletzko, Berthold

doi:10.1159/000439491

Cited by 11 publications

(8 citation statements)

References 30 publications

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“…alanine, glutamate/glutamine), C3 and C5 acylcarnitines, and aromatic amino acids (phenylalanine and tyrosine) 29 , 39 – 44 . The increase in BCAA and short-chain acylcarnitine concentrations is linked to elevated protein intake 45 , and levels are positively correlated with adiposity 46 , 47 and strongly associated with IR 29 , 32 , 44 , 48 . The metabolic environment in LGA is less well-known.…”

Section: Discussionmentioning

confidence: 99%

Similarities between acylcarnitine profiles in large for gestational age newborns and obesity

Sánchez‐Pintos

Castro

Roca

et al. 2017

Sci Rep

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Large for gestational age (LGA) newborns have an increased risk of obesity, insulin resistance, and metabolic syndrome. Acylcarnitine profiles in obese children and adults are characterized by increased levels of C3, C5, and certain medium-chain (C12) and long-chain (C14:1 and C16) acylcarnitines. C2 is also increased in insulin-resistant states. In this 1-year observational study of 2514 newborns (246 LGA newborns, 250 small for gestational age (GA) newborns, and 2018 appropriate for GA newborns), we analyzed and compared postnatal acylcarnitine profiles in LGA newborns with profiles described for obese individuals. Acylcarnitine analysis was performed by tandem mass spectrometry on driedblood spots collected on day 3 of life. LGA newborns had higher levels of total short-chain acylcarnitines (p < 0.001), C2 (p < 0.01) and C3 (p < 0.001) acylcarnitines, and all C12, C14, and C16 acylcarnitines except C12:1. They also had a higher tendency towards carnitine insufficiency (p < 0.05) and carnitine deficiency (p < 0.001). No significant differences were observed between LGA newborns born to mothers with or without a history of gestational diabetes. This novel study describes a postnatal acylcarnitine profile in LGA with higher levels of C2, C3, total acylcarnitines, and total short-chain acylcarnitines that is characteristic of childhood and adult obesity and linked to an unhealthy metabolic phenotype.

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Section: Discussionmentioning

confidence: 99%

Similarities between acylcarnitine profiles in large for gestational age newborns and obesity

Sánchez‐Pintos

Castro

Roca

et al. 2017

Sci Rep

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“…Among all the modern "omics" techniques, metabolomics is closest to the human phenotype: the degree of association to phenotype and health generally increases from genomics, to epigenomics, transcriptomics, proteomics, and finally to metabolomics. We apply high-performance liquid chromatography (LC) coupled to triple quadrupole mass spectrometry (MS/MS), which en-ables us to quantify hundreds of molecules in small biological samples, e.g., 50 μL plasma or less [12][13][14][15][16][17][18] . The pattern of metabolites determined, which include substrates, intermediates, and products of biological processes, can provide biomarkers of exposures and outcomes, and it can allow insights into underlying metabolic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Regulation of Pre- and Postnatal Growth

Koletzko¹,

Kirchberg²,

Hellmuth³

et al. 2018

Recent Research in Nutrition and Growth

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Growth characteristics during periods of early developmental plasticity are linked with later health outcomes and with disease risks. Infant growth is modulated by genetic and exogenous factors including nutrition. We try to explore their underlying mechanisms using targeted metabolomic profiling of small molecules in biological samples using high-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) to quantify hundreds of molecules in small biosamples, e.g., 50 µL plasma. In the large German LISA birth cohort study, cord blood lysophosphatidylcholines and fatty acids were closely associated with infant birth weight, with a nonsignificant trend towards an association with infant weight gain and later BMI. Studies in infants randomized to different protein intakes in the European CHOP Study show conventional high protein intakes to markedly increase plasma-indispensable amino acids (AA), particularly branched-chain AA (BCAA), while exceeding the infant's capacity of BCAA breakdown, and an increase in the dispensable AA tyrosine previously associated with insulin resistance. In a path model analysis of the relationship of infant plasma AA, growth factors, and infant growth, AA were generally found to induce a stronger response of insulin than IGF-I although effects of individual AA were very different. We conclude that targeted improvement in nutrient supply in pregnancy and infancy may offer large opportunities for promoting desirable child growth patterns and long-term health.

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“…Further, TGFβ2-associated bacteria were involved in a wide range of metabolic functions, including steroid and flavonoid biosynthesis, which may contribute to metabolic profile differentiation induced by breastfeeding compared to formula-feeding (38). Additionally, given that several studies have found a protective effect of TGFβ1 and TGFβ2 against atopic disorders (19)—consistent with what we have previously found in this cohort (39)—it is conceivable that neonatal gut microbiota may partially mediate this association.…”

Section: Discussionmentioning

confidence: 99%

Breast Milk Transforming Growth Factor β Is Associated With Neonatal Gut Microbial Composition

Sitarik

Bobbitt²,

Havstad³

et al. 2017

J. pediatr. gastroenterol. nutr.

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Objectives Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. While breastfeeding is known to impact neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated three essential breast milk cytokines and their association with early life gut microbiota. Methods A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk TGFβ1, TGFβ2, and IL-10 were assayed using ELISAs, while neonatal gut microbiome was profiled using 16S rRNA sequencing. Results Individually, immunomodulators TGFβ1 and TGFβ2 were significantly associated with neonatal gut microbial composition (R2=0.024, p=0.041; R2=0.026, p=0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. However, the effects of TGFβ1 and TGFβ2 were not independent of one another, and the effect of TGFβ2 was stronger than that of TGFβ1. Higher levels of TGFβ2 was associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. Conclusions Breast milk TGFβ concentration explains a portion of variability in gut bacterial microbiota composition among breastfed neonates. Whether TGFβ acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breastfeeding affects the gut microbiome—and potentially immune development—in early life.

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Effects of Early Nutrition on the Infant Metabolome

Cited by 11 publications

References 30 publications

Similarities between acylcarnitine profiles in large for gestational age newborns and obesity

Similarities between acylcarnitine profiles in large for gestational age newborns and obesity

Metabolic Regulation of Pre- and Postnatal Growth

Breast Milk Transforming Growth Factor β Is Associated With Neonatal Gut Microbial Composition

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