2013 Annual Report
1a.Objectives (from AD-416):
There is an ongoing need to enhance our understanding of the role of various nutrients on fetal, postnatal, and childhood growth and development. This is becoming increasingly important as studies continue to show an association between the patterns of growth during these early time periods and health later in life. At present, little is known about the functional need for different amino acids in support of these changes, and the variability in normal growth. The research objectives include:.
1)define the nutritional and functional requirements of methionine, cysteine, and arginine for healthy children;.
2)investigate the impact of docosahexaenoic acid (DHA) intake from food and supplemental sources on blood levels, cognitive performance, and neurophysiological function, heart rate and blood pressure, as well as a lower incidence of allergies and upper respiratory infection in children;.
3)investigate the pathways and nutritional modulation of methyl group production in underweight and normal weight pregnant women;.
4)investigate differences in bowel flora, antioxidant capacity, and mitochondrial integrity between severely malnourished and well-nourished children;.
5)conduct a pilot study of genetic susceptibility to edematous severe child malnutrition (ESCM);.
6)conduct exploratory analyses of the relationship between risk of ESCM and individual genetic variation;.
7)critically evaluate population-specific genetic variation in samples;.
8)determine how obesity, ethnicity, and obesity-related liver disease contribute to low serum 25-hydroxyvitamin D levels;.
9)understand the relationship between serum 25-hydroxyvitamin D levels and serum inflammatory cytokines, gastronintestinal permeability, and elevated liver transaminases; 10) characterize glucose and insulin tolerance, serum and liver lipids, and liver histology and gene expression; and 11) explore the molecular mechanisms for the lipotropic and anti-diabetic effects. This project will provide novel and new information directly useful to nutritional scientists, pediatricians, industry, and governmental agencies responsible for establishing pediatric dietary guidelines. These data will have global application and provide a strong basis for evidence-based development of nutritional recommendations for children and pregnant mothers.
1b.Approach (from AD-416):
The goal of our research is to obtain better data on amino acid nutritional and functional requirements for growth. Our researchers aim to determine if an intake of methionine and cysteine is more efficient to support glutathione synthesis rates in healthy children, than an equimolar intake of methionine alone. We will evaluate whether arginine supplementation in obese children improves insulin sensitivity and protein synthesis, and explore gluconeogenesis under these conditions. We will investigate the impact of docosahexaenoic acid (DHA) intake from food and supplemental sources on blood levels, cognitive performance, and neurophysiological function of 4- to 12-year-old children. We will advance our understanding of the genetic determinants of risk of ESCM which will provide new insights into the causes of ESCM. Through our studies of Vitamin Din different ethnic groups of obese children, we will contribute to new insights into the actions of vitamin D and the pathogenesis of obesity related liver disease in children. Additionally we will identify novel dietary supplement strategies to prevent or treat obesity related chronic diseases by evaluating the lipotropic effect.
Significant research progress was accomplished during the year. To review the
progress, please refer to project 6250-51000-052-20S (Project 2).
Does gut bacteria change with age? The trillions of bacteria in our gut are
critically important in helping us digest food, make important nutrients that are
vital to our health, and help our immune systems develop and work properly.
Scientists at the Children's Nutrition Research Center in Houston, Texas, learned
that, in contrast to what was previously thought, the types of bacteria in our gut
continue to evolve throughout childhood. These findings will help researchers better
understand the factors that control digestion and utilization of dietary nutrients.
Additionally scientists will better understand the role of gut bacteria in the
changes in the immune system that occur with age.
Gut bacteria are related to symptoms after eating. Evidence suggests that diet is an
important factor in how a person feels after eating, but many unanswered questions
remain. Scientists at the Children's Nutrition Research Center in Houston, Texas,
found that the types of bacteria in our gut may be related to symptoms of indigestion such as belly pain after eating certain foods. By evaluating the diet of children at different ages as well as their gut bacteria, we will begin to understand more fully the way diet and the gut bacteria are interrelated across different child ages and their impact on indigestion. That will help us to design healthier diets that also are less likely to cause stomach upset.
Increasing dietary fiber changes the population of bacteria in the gut. Individuals
are encouraged to increase fiber in our diet because studies suggest that it benefits our health. Studies 50 years ago suggested that the gut bacteria help us digest the fiber we eat. However, by using cutting edge molecular techniques, we can understand how dietary fiber and bacteria interact in ways never before possible. Scientists at the Children's Nutrition Research Center in Houston, Texas, learned that eating fiber causes dramatic shifts in the types of gut bacteria. Using other advanced techniques, we are currently studying how this change in gut bacteria population affects our health. Findings from this work will help researchers develop correlations of specific gut bacteria genes may have on our health.
Role of bacteria in severe malnutrition. Scientists are puzzled as to why some
children fed the same diet develop severe malnutrition, while others do not.
Researchers at the Children's Nutrition Research Center in Houston, Texas, looked at
bacteria from twins where one of the twins developed severe malnutrition while the
other remained well nourished were identified by deep sequencing of stool specimens.
Very different bacterial populations were seen between the twins, and a distinct
pattern of bacteria was seen in stool from children with severe malnutrition. This
insight of different bacterial populations despite similiar diets may lead to new
treatments for malnutrition that not only provide missing nutrients, but change
bacterial populations in the gut.
Badaloo, A.V., Forrester, T., Reid, M., Jahoor, F. 2012. Nutritional repletion of children with severe acute malnutrition does not affect VLDL apolipoprotein B-100 synthesis rate. Journal of Nutrition. 142(5):931-935.
Jahoor, F. 2012. Effects of decreased availability of sulfur amino acids in severe childhood undernutrition. Nutrition Reviews. 70(3):176-187.
Yatsunenko, T., Rey, F.E., Manary, M.J., Trehan, I., Dominquez-Bello, M.G., Contreras, M., Magris, M., Hidalgo, G., Baldassano, R.N., Anokhin, A.P., Heath, A.C., Warner, B., Reeder, J., Kuczynski, J., Caporaso, J.G., Lozupone, C.A., Lauber, C., Clemente, J.C., Knights, D., Knight, R., Gordon, J.I. 2012. Human gut microbiome viewed across age and geography. Nature. 486(7402):222-227.
Badaloo, A., Hsu, J.W., Taylor-Bryan, C., Green, C., Reid, M., Forrester, T., Jahoor, F. 2012. Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema. American Journal of Clinical Nutrition. 95(1):84-90.
Lin, A., Nichols, B.L., Quezada-Calvillo, R., Avery, S.E., Sim, L., Rose, D.R., Naim, H.Y., Hamaker, B.R. 2012. Unexpected high digestion rate of cooked starch by the Ct-Maltase-Glucoamylase small intestine mucosal alpha-glucosidase subunit. PLoS One. 7(5;e35473):1-7.
Voss, J., Goo, Y.A., Cain, K., Woods, N., Jarrett, M., Smith, L., Shulman, R., Heitkemper, M. 2011. Searching for the noninvasive biomarker Holy Grail: Are urine proteomics the answer? Biological Research for Nursing. 13(3):235-242.
Carvalho, C.M., Ramocki, M.B., Pehlivan, D., Franco, L.M., Gonzaga-Jauregui, C., Fang, P., McCall, A., Karman Pivnick, E., Hines-Dowell, S., Seaver, L.H., Friehling, L., Lee, S., Smith, R., Del Gaudio, D., Withers, M., Liu, P., Cheung, S., Belmont, J., Zoghbi, H.Y., Hastings, P.J., Lupski, J.R. 2011. Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genome. Nature Genetics. 43(11):1074-1079.
Marian, A.J., Belmont, J. 2011. Strategic approaches to unraveling genetic causes of cardiovascular diseases. Circulation Research. 108(10):1252-1269.
Lupski, J.R., Belmont, J.W., Boerwinkle, E., Gibbs, R.A. 2011. Clan genomics and the complex architecture of human disease. Cell. 147(1):32-43.
Grover, M., Brunetti-Pierri, N., Belmont, J., Phan, K., Tran, A., Shypailo, R.J., Ellis, K.J., Lee, B.H. 2012. Assessment of bone mineral status in children with Marfan syndrome. American Journal of Medical Genetics. 158A(9):2221-2224.
Saulnier, D.M., Ringel, Y., Heyman, M.B., Foster, J.A., Bercik, P., Shulman, R.J., Versalovic, J., Verdu, E.F., Dinan, T.G., Hecht, G., Guarner, F. 2013. The intestinal microbiome, probiotics and prebiotics in neurogastroenterology. Gut Microbes. 4(1):17-27.
Patel, S.G., Hsu, J.W., Jahoor, F., Coraza, I., Bain, J.R., Stevens, R.D., Iyer, D., Nalini, R., Ozer, K., Hampe, C.S., Newgard, C.B., Balasubramanyam, A. 2013. Pathogenesis of A-beta+ ketosis-prone diabetes. Diabetes. 62(3):912-922.
Lagrone, L.N., Trehan, I., Meuli, G.J., Wang, R.J., Thakwalakwa, C., Maleta, K., Manary, M.J. 2012. A novel fortified blended flour, corn-soy blend "plus-plus," is not inferior to lipid-based ready-to-use supplementary foods for the treatment of moderate acute malnutrition in Malawian children. American Journal of Clinical Nutrition. 95(1):212-219.
Jones, K., Sim, L., Mohan, S., Kumarasamy, J., Liu, H., Avery, S., Naim, H.Y., Quezada-Calvillo, R., Nichols, B.L., Pinto, B., Rose, D.R. 2011. Mapping the intestinal alpha-glucogenic enzyme specificities of starch digesting maltase-glucoamylase and sucrase-isomaltase. Bioorganic and Medicinal Chemistry. 19(13):3929-3934.