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United States Department of Agriculture

Agricultural Research Service

Research Project: CLINICAL INVESTIGATIONS ON NUTRITION AND CHILD DEVELOPMENT

Location: Children's Nutrition Research Center

Project Number: 6250-51000-052-20
Project Type: Specific Cooperative Agreement

Start Date: Apr 01, 2009
End Date: Mar 31, 2014

Objective:
Obj. 1: No longer applies. Obj. 2: Investigate the pathways and nutritional modulation of methyl group production in under- and normal weight pregnant women. Sub-Obj 2A. Determine whole body protein kinetics, methionine kinetics and transmethylation, an index of methyl production and utilization, serine and glycine fluxes, indices of production rates of methyl group precursors, and conversion of serine to glycine, and glycine to CO2, indices of methyl group supply from these precursors to the transmethylation pathway, in under- and normal-weight pregnant women. Sub-Obj 2B. Determine the effect of dietary supplementation with sulfur amino acid-rich whey protein vs. legume/cereal protein on methionine production and transmethylation rate and on serine and glycine fluxes in underweight pregnant women. Sub-Obj 2C. Determine methionine kinetics and transmethylation rates during the first trimester in groups of underweight pregnant women with either normal or low plasma vitamin B12 concentration, after dietary supplementation with Vitamin B12. Sub-Obj 2D. Determine methionine kinetics and transmethylation rates in underweight pregnant women with either normal or low plasma folate concentration after dietary supplementation with folate.Obj. 3: Investigate differences in bowel flora, antioxidant capacity, and mitochondrial integrity between severely malnourished and well-nourished children. Sub-Obj 3A. Measure the populations of bacterial divisions and species in bowel flora populations in children as well as bowel flora diversity with edematous as well as non-edematous SCU and in well-nourished children. Sub-Obj 3B. Measure antioxidant capacity and mitochondrial integrity, as well as characterize the immune system in children with edematous vs. non-edematous SCU. Obj. 4: Initiate a pilot study of genetic susceptibility to ESCM. Obj. 5: Conduct exploratory analyses of the relationship between risk of ESCM and individual genetic variation. Obj. 6: Evaluate population-specific genetic variation. Obj. 7: Characterize the developmental profile of the GI microbiome and transcriptome in healthy, term infants. Obj. 8: Compare the effect of breast versus bottle-feeding on the development of GI microbiome and lactose digestion/absorption. Obj. 9: Profile changes in the GI microbiome in response to the introduction of weaning foods such as dietary starch in the form of cereal. Obj. 10: detect gene-gene/environment interactions.

Approach:
Whole body protein kinetics, methionine production and transmethylation, serine and glycine fluxes, and conversion of serine to glycine and glycine to carbon dioxide will be measured in groups of Indian women with low (=18.5) and normal (>18.5 = 25) BMI between 10 and 12 weeks of pregnancy and again at 26-28 weeks. These measurements plus maternal gestational weight gain, neonate gestational age, birth weight, length, and head circumference will be repeated in groups with BMIs =18.5 after dietary supplement with more energy and protein and in those women with low blood vitamin B12 and folate, after 16 weeks of supplementation with vitamin B12 and folate. Additional studies will evaluate 6- to 24-month twins who are at high risk for malnutrition. Stool samples will be collected in a disposable diaper for multiplex pyrosequencing of bacterial 16S rRNA genes present in gut microbial communities and pyrosequencing of total community DNA (the gut microbiome). A second study will be performed in 50 severely undernourished, 6- to 12-month-old children who are receiving therapeutic food to promote rapid catch-up growth. Antioxidant capacity will be assessed by whole blood glutathione, erythrocyte superoxide dismutase, erythrocyte glutathione peroxidase, and serum oxidized proteins. Mitochondrial integrity will be assessed by lactate and the copy numbers of mitochondrial DNA/RNA in peripheral monocytes, measured by real time duplex nucleic acid sequence-based amplification. To assess how immune response varies with nutritional state, a panel of 27 cytokines will be assessed. Collect data on genetic susceptibility to ESCM and other phenotypes that result from malnutrition using cutting-edge genomics tools and methods in human genetics. Cutting edge technology will be utilized to address this significant global health/nutritional concern. Utilize models to identify genotype associations.

Last Modified: 8/27/2014
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