Location: Children's Nutrition Research Center
2020 Annual Report
Objectives
A number of pressing nutritional issues face mankind. In the US and other developed countries strategies are needed to address the ever-increasing epidemic of obesity and related chronic diseases and in impoverished countries severe acute malnutrition directly contributes to deaths of more than a million children under the age of 5 each year globally. To address these concerns researchers will conduct the following objectives: 1) compare the effects of inulin and fructo-oligosaccharides against a maltodextrin placebo in obese children, using a double-blind randomized controlled trial, to study weight loss, fecal microbiota and their functions; 2) among children from low-to-middle income countries with severe acute malnutrition (SAM) to: a) longitudinally characterize epigenomic, and metabolomic responses to SAM treatment; b) assess amino acid content of hair samples taken before, during, and after therapy to identify biochemical markers of nutritional status and therapeutic response, and; c) investigate the role of a newly identified hormone – Asprosin – in the recovery of satiety during SAM refeeding therapy by integrating serial measurements in plasma with clinical nutritional data on caloric intake and weight recovery; and 3) conduct a clinical trial adding black-eyed peas to diets of young children at risk for stunting. Determine efficacy in reducing stunting and analyze fecal sample to understand potential mechanisms by which the food supplement ameliorates stunting. Assess dietary compliance in a novel, quantitative manner using a urinary biomarker for black eyed peas. Currently quercetin and ferulic acid are candidates for this biomarker. Additionally, breastfeeding has enormous health benefits to both infant and mother and continued efforts to understand the biology of mammary development and lactation are important to improving both infant and maternal health. Thus we will undertake this objective to further our knowledge: 4) select inbred mouse strains with phenotypic extremes in milk production will be used to: a) identify genomic variants along with intestinal and mammary-expressed genes that differentiate low and high milk production, and b) determine the extent to which genome-driven differences in milk production and mammary gene expression are directly mediated through host-dependent differences in the intestinal and/or mammary tissue microbiome.
Approach
A multi-discipline approach will be undertaken to address these nutritional concerns. Hispanic children ages 7-18 years of age will be enrolled in the study, anthropometric measurements and blood draws will be taken and analyzed. Urine and stool samples will be collected and analysis will be performed to account for inulin and B-defensin. Researchers will also assess the pre- and post-treatment serum samples from a recently concluded study of 1-carbon metabolites. We will perform laboratory procedures to assess DNA methylation from the samples collected. Scientists will conduct a randomized, double blind, clinical controlled trial in south central Mali among healthy 6-12 month old children by adding black-eyed peas to diets of young children at risk for stunting. Scientists will analyze urinary and fecal samples to understand potential mechanisms by which the food supplement reduces stunting. And finally, researchers will use genome-wide pathway association study approaches in conjunction with bioinformatics tools to predict the functional consequences of the private alleles within the lactation phenome strains to better understand the phenotypic expression of increased lactation.
Progress Report
To review the progress made during the year, please refer to the following projects: 3092-51000-062-01S (Project #1), 3092-51000-062-03S (Project #2), and 3092-51000-062-04S (Project #3).
Accomplishments
1. The strength of the gut barrier differs between boys and girls. According to the latest Centers for Disease Control (CDC) report, the prevalence of obesity in children that are 12-19 years of age is 21%. Obesity is associated with a number of healthy complications, and in children, liver disease is prominent, particularly in boys versus girls. Recent studies show that gut bacteria can contribute to the development of liver disease related to obesity. However, the stronger the gut barrier, the less likely gut bacteria and their potentially toxic products can enter the bloodstream, contributing to liver disease. Researchers in Houston, Texas, conducted studies that have shown that the gut barrier is weaker in boys than in girls. This may be part of the reason why boys are more at risk for liver disease related to obesity.
Review Publications
Burrin, D.G., Sangild, P., Stoll, B., Thymann, T., Buddington, R., Marini, J., Olutoye, O., Shulman, R. 2020. Translational advances in pediatric nutrition and gastroenterology: New insights from pig models. Annual Review of Animal Biosciences. 8(321):354. https://doi.org/10.1146/annurev-animal-020518-115142.
Huang, J., Dai, B., Qu, H., Zhong, Y., Ma, Y., Luo, J., Hadsell, D., Shi, H. 2020. Epidermal growth factor stimulates fatty acid synthesis mainly via PLC-y1/Akt signaling pathway in dairy goat mammary epithelial cell. Animals. 10(6):930. https://doi.org/10.3390/ani10060930.
Terefe, Y., Deblais, L., Ghanem, M., Helmy, Y.A., Mummed, B., Chen, D., Singh, N., Ahyong, V., Kalantar, K., Yimer, G., Hassen, J.Y., Mohammed, A., McKune, S.L., Manary, M.J., Ordiz, M.I., Gebreyes, W., Havelaar, A.H., Rajashekara, G. 2020. Co-occurrence of campylobacter species in children from Eastern Ethiopia, and their association with environmental enteric dysfunction, diarrhea, and host microbiome. Frontiers in Public Health. 8:99. https://doi.org/10.3389/fpubh.2020.00099.
Hendrixson, D.T., Godbout, C., Los, A., Callaghan-Gillespie, M., Mui, M., Wegner, D., Bryant, T., Koroma, A., Manary, M.J. 2020. Treatment of severe acute malnutrition with oat or standard ready-to-use therapeutic food: A triple-blind, randomised controlled clinical trial. Gut. https://doi.org/10.1136/gutjnl-2020-320769.
Balamurugan, R., Pugazhendhi, S., Balachander, G.M., Dharmalingam, T., Mortimer, E.K., Gopalsamy, G.L., Woodman, R.J., Meng, R., Alpers, D.H., Manary, M., Binder, H.J., Brown, I.L., Young, G.P., Ramakrishna, B.S. 2019. Effect of native and acetylated dietary resistant starches on intestinal fermentative capacity of normal and stunted children in Southern India. International Journal of Environmental Research and Public Health. 16(20):3922. https://doi.org/10.3390/ijerph16203922.
Manary, M., Callaghan-Gillespie, M. 2020. Role of optimized plant protein combinations as a low-cost alternative to dairy ingredients in foods for prevention and treatment of moderate acute malnutrition and severe acute malnutrition. Nestle Nutrition Workshop. 93:111-120. https://doi.org/10.1159/000503347.
Grenov, B., Larnkjaer, A., Lee, R., Serena, A., Molgaard, C., Michaelsen, K.F., Manary, M.J. 2020. Circulating insulin-like growth factor-1 is positively associated with growth and cognition in 6- to 9-year-old schoolchildren from Ghana. Journal of Nutrition. 150(6):1405-1412. https://doi.org/10.1093/jn/nxaa075.
Ordiz, M.I., Janssen, S., Humphrey, G., Ackermann, G., Stephenson, K., Agapova, S., Divala, O., Kaimila, Y., Maleta, K., Zhong, C., Knight, R., Trehan, I., Tarr, P.I., Rusconi, B., Manary, M.J. 2020. The effect of legume supplementation on the gut microbiota in rural Malawian infants aged 6 to 12 months. American Journal of Clinical Nutrition. 111(4):884-892. https://doi.org/10.1093/ajcn/nqaa011.
Roediger, R., Stein, H.H., Callaghan-Gillespie, M., Blackman, J.K., Kohlmann, K., Maleta, K., Manary, M. 2020. Protein quality in ready-to-use supplementary foods for moderate wasting. Maternal and Child Nutrition. e13019. https://doi.org/10.1111/mcn.13019.
Pitman, R.T., Mui, M., Michelson, P.H., Manary, M.J. 2019. Ready-to-use supplemental food for nutritional supplementation in cystic fibrosis. Current Developments in Nutrition. 3(5):nzz016. https://doi.org/10.1093/cdn/nzz016.
Ordiz, M.I., Semba, R.D., Moaddel, R., Rolle-Kampczyk, U., Von Bergen, M., Herberth, G., Khadeer, M., Roder, S., Manary, M.J. 2019. Serum amino acid concentrations in infants from Malawi are associated with linear growth. Current Developments in Nutrition. 3(10):nzz100. https://doi.org/10.1093/cdn/nzz100.
Grover, M., Dasari, S., Bernard, C.E., Chikkamenahalli, L.L., Yates, K.P., Pasricha, P.J., Sarosiek, I., McCallum, R., Koch, K.L., Abell, T.L., Kuo, B., Shulman, R.J., Gibbons, S.J., McKenzie, T.J., Kellogg, T.A., Kendrick, M.L., Tonascia, J., Hamilton, F.A., Parkman, H.P., Farrugia, G. 2019. Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis. American Journal of Physiology - Gastrointestinal and Liver Physiology. 317(5):G716-G726. https://doi.org/10.1152/ajpgi.00115.2019.
Cruz, L.A., Minard, C., Guffey, D., Chumpitazi, B.P., Shulman, R.J. 2020. Does a minority of children with functional gastrointestinal disorders receive formal diet advice?. Journal of Parenteral and Enteral Nutrition. https://doi.org/10.1002/jpen.1771.
Shulman, R.J., Devaraj, S., Heitkemper, M. 2019. Gut permeability is affected by sex and increased in children with irritable bowel syndrome but not in functional abdominal pain. Neurogastroenterology & Motility. 32(3):e13765. https://doi.org/10.1111/nmo.13765.
McOmber, M., Rafati, D., Cain, K., Devaraj, S., Weidler, E.M., Heitkemper, M., Shulman, R.J. 2020. Increased gut permeability in first-degree relatives of children with irritable bowel syndrome or functional abdominal pain. Clinical Gastroenterology and Hepatology. 18(2):375-384. https://doi.org/10.1016/j.cgh.2019.05.011
Alfaro-Cruz, L., Kaul, I., Zhang, Y., Shulman, R.J., Chumpitazi, B.P. 2019. Assessment of quality and readability of internet dietary information on irritable bowel syndrome. Clinical Gastroenterology and Hepatology. 17(3):566-567. https://doi.org/10.1016/j.cgh.2018.05.018.
Song, A., Dai, W., Jang, M., Medrano, L., Li, Z., Zhao, H., Shao, M., Tan, J., Li, A., Ning, T., Miller, M.M., Armstrong, B., Huss, J.M., Zhu, Y., Liu, Y., Gradinaru, V., Wu, X., Jiang, L., Scherer, P.E., Wang, Q.A. 2019. Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue. Journal of Clinical Investigation. 130(1):247-257. https://doi.org/10.1172/JCI129167.
Zhao, S., Li, N., Zhu, Y., Straub, L., Zhang, Z., Wang, M., Zhu, Q., Kusminski, C.M., Elmquist, J.K., Scherer, P.E. 2020. Partial leptin deficiency confers resistance to diet-induced obesity in mice. Molecular Metabolism. 37:100995. https://doi.org/10.1016/j.molmet.2020.100995.
Desai, C., Handley, S., Rodgers, R., Rodriguez, C., Ordiz, M.I., Manary, M.J., Holtz, L.R. 2020. Growth velocity in children with environmental enteric dysfunction is associated with specific bacterial and viral taxa of the gastrointestinal tract in Malawian children. PLOS Neglected Tropical Diseases. 14(6):e0008387. https://doi.org/10.1371/journal.pntd.0008387.
Chase, R.P., Kerac, M., Grant, A., Manary, M., Briend, A., Opondo, C., Bailey, J. 2020. Acute malnutrition recovery energy requirements based on mid-upper arm circumference: Secondary analysis of feeding program data from 5 countries, Combined Protocol for Acute Malnutrition Study (ComPAS) Stage 1. PLoS One. 15(6):e0230452. https://doi.org/10.1371/journal.pone.0230452.
Kamp, K.J., Han, C., Shulman, R.J., Cain, K.C., Barney, P., Opp, M.R., Chang, L., Burr, R.L., Heitkemper, M.M. 2020. Cytokine levels and symptoms among women with irritable bowel syndrome: Considering the role of hormonal contraceptive use. Biological Research for Nursing. https://doi.org/10.1177/1099800420941252.
Kamp, K.J., Cain, K.C., Utleg, A., Burr, R.L., Raftery, D., Luna, R., Shulman, R.J., Heitkemper, M.M. 2020. Bile acids and microbiome among individuals with irritable bowel syndrome and healthy volunteers. Biological Research for Nursing. https://doi.org/10.1177/1099800420941255.
Hollier, J.M., Czyzewski, D.I., Self, M.M., Liu, Y., Weidler, E.M., Van Tilburg, M.A., Varni, J.W., Shulman, R.J. 2020. Associations of abdominal pain and psychosocial distress measures with health-related quality-of-life in pediatric healthy controls and irritable bowel syndrome. Journal of Clinical Gastroenterology. https://doi.org/10.1097/MCG.0000000000001373.
Bailey, J., Opondo, C., Lelijveld, N., Marron, B., Onyo, P., Musyoki, E.N., Adongo, S.W., Manary, M., Briend, A., Kerac, M. 2020. A simplified, combined protocol versus standard treatment for acute malnutrition in children 6–59 months (ComPAS trial): A cluster-randomized controlled non-inferiority trial in Kenya and South Sudan. PLoS Medicine. https://doi.org/10.1371/journal.pmed.1003192.
Shulman, R.J., Self, M.M., Czyzewski, D.I., Goldberg, J., Heitkemper, M. 2020. The prevalence of hypermobility in children with irritable bowel syndrome and functional abdominal pain is similar to that in healthy children. Journal of Pediatrics. 222:134-140. https://doi.org/10.1016/j.jpeds.2020.03.033.
Febo-Rodriguez, L., Chumpitazi, B.P., Shulman, R.J. 2019. Childhood gastroparesis is a unique entity in need of further investigation. Neurogastroenterology & Motility. 32:e13699. https://doi.org/10.1111/nmo.13699.
Alfaro-Cruz, L., Heitkemper, M., Chumpitazi, B.P., Shulman, R.J. 2020. Dietary intervention adherence and adherence barriers in functional gastrointestinal disorder studies. Journal of Clinical Gastroenterology. 54(3):203-211. https://doi.org/10.1097/MCG.0000000000001280.
Schulze, K.V., Swaminathan, S., Howell, S., Jajoo, A., Lie, N.C., Brown, O., Sadat, R., Hall, N., Marshall, K., May, T., Reid, M.E., Taylor-Bryan, C., Wang, X., Belmont, J.W., Guan, Y., Manary, M.J., Trehan, I., McKenzie, C.A., Hanchard, N.A. 2019. Edematous severe acute malnutrition is characterized by hypomethylation of DNA. Nature Communications 10(1):5791 https://doi.org/10.1038/s41467-019-13433-6
