A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming
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PROVIDER: PRJNA1085285 | ENA |
REPOSITORIES: ENA
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Project description:A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N+WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N+WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P<0.01), elevated post-stressor cortisol (0.24 log µg/dl; P<0.01), higher cortisol residualized gain scores (0.06 µg/dl; P=0.023), and decreased methylation of the NGFI-A binding site (-0.04; P=0.037). The N+WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.
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Project description:Nutritional programming takes place in early development. Variation in the quality and/or quantity of nutrients in early development can influence long-term health and viability. However, little is known about the mechanism of nutritional programming. The live-bearing fish Xiphophorus multilineatus, has the potential to be a new model for understanding these mechanisms, given evidence of both genetic and nutritional programming influences on juvenile growth rate. To study the molecular signatures of nutritional programming, we assembled a de novo transcriptome for X. multilineatus, and used RNA-Seq to profile gene expression in the brains of males reared in low and high quality juvenile environments. We found131 genes were differentially expressed, including metabolism and appetite master regulator agrp gene.
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Project description:Nutrient deficiency during perinatal development is associated with an increased risk to develop obesity, diabetes and hypertension in adulthood. However, the molecular mechanisms underlying the developmental programming of the metabolic syndrome remain largely unknown. Given the essential role of the hypothalamus in the integration of nutritional, endocrine and neuronal cues, here we have analyzed the profile of the hypothalamus transcriptome in 180-day-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet throughout pregnancy and lactation. From a total of 26,209 examined genes, 688 were up-regulated and 309 down-regulated (P<0.003) by early protein restriction. Based on the hypothesis that variations in gene expression levels often reflect changes in gene’s activity and that transcriptional networks are at the heart of physiological functions, we identified two gene clusters regulating common cellular processes whose expression is coordinately regulated by perinatal protein restriction. The first one is constituted by several genes of the insulin signaling pathway which, additionally, act as gatekeeper genes for regulation of nutrient sensing. The second cluster encompasses a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel which, in addition, link temporal and nutritional cues to metabolism through their tight interaction with the circadian clock. Collectively, these results indicate that the programming of the hypothalamic circuits regulating energy homeostasis is a key step in the development of obesity associated with malnutrition in early life and provide a valuable starting point for the direct and systematic experimental analysis of the role of the hypothalamus in the physiopathological disturbances associated with the programming of the metabolic syndrome. Five rats fed a control diet, and five rats fed a low-protein diet. All rats are male.
2010-07-02 | E-GEOD-22540 | biostudies-arrayexpress
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2023-06-01 | GSE229947 | GEO
Project description:Rising ambient temperatures represent an imminent risk to pregnant women and infants. Both maternal malnutrition and heat stress during pregnancy contribute to poor fetal growth, the leading cause of diminished child development in low-resource settings. However, studies explicitly examining interactions between these two important environmental factors are lacking. We leveraged maternal and neonatal anthropometry data from a randomized controlled trial focused on improving preconception maternal nutrition (Women First Preconception Nutrition trial) conducted in Thatta Pakistan, where both nutritional deficits and heat stress are prevalent. Multiple linear regression of ambient temperature and neonatal anthropometry at birth (n = 459) showed a negative association between daily maximal temperatures in the first trimester and z-scores of birth length (LGAZ) and head circumference (HCGAZ). Placental mRNA-sequencing and protein analysis showed transcriptomic changes in protein translation, ribosomal proteins and mTORC1 signalling components in term placenta exposed to excessive heat in the first trimester. Targeted metabolomic analysis indicated ambient temperature associated alterations in maternal circulation with decreases in choline concentrations. Notably, negative impacts of heat on birth length were in part mitigated in women randomized to comprehensive maternal nutritional supplementation (MNS) before pregnancy suggesting potential interactions between heat stress and nutritional status of the mother. Collectively the findings bridge critical gaps in our current understanding of how maternal nutrition may provide resilience against adverse effects of heat stress in pregnancy.
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2019-11-01 | GSE130722 | GEO
Project description:Developmental programming is the concept that environmental factors, particularly during foetal life, can alter development, metabolism and physiology of an organism and this can have consequences later in life. There is growing interest in developmental programming in livestock species, particularly effects of maternal pregnancy nutrition, which is easy to manipulate. Recent research, using a sheep model, has shown that milk production in ewe offspring may be susceptible to maternal nutritional programming, such that over nutrition (ad libitum) of the pregnant dam, compared with maintenance nutrition, may impair their first lactation performance and result in the weaning of lighter lambs. RNA-seq was performed to identify gene expression differences as a result of maternal nutrition in ewe offspring during their first parity. Samples were collected in late pregnancy and during lactation, allowing us to examine gene expression changes during maturation of the ovine mammary gland. Three biological replicates were sequenced for each of the treatment conditions (maternal nutrition: sub-maintenance, maintenance, and ad libitum) and time points (late pregnancy and lactation). Each biological replicate consisted of RNA from multiple individuals (late pregnancy n=3, lactation n=2).
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