Location: Children's Nutrition Research Center
2021 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) removed due to scientists departure; 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. Measurement of B-defensin-2 in stool. The human intestine is comprised of trillions of bacteria, which can affect the function of the immune system since the largest collection of immune cells is also in the intestines. Any treatment that affects the bacteria in the intestines, such as probiotics or a significant diet change, can alter the types of bacteria in the gut and hence the immune system can be affected. Therefore, a test of immune system activity in the intestine is needed. Researchers in Houston, Texas, developed a test that measures a specific protein called B-defensin-2, which is an important part of the immune system in the gut. This analysis can detect changes in the activation of the immune system in children with different types of intestinal disorders. This information will help determine how different nutrients affect the function of the immune system in the gut which impacts the individual's overall health.
2. Adipocyte Connexin43 gap junctions mediate breast milk nutritional composition. Nutritious breast milk is vital to support newborn growth and development. The mother's adipose tissue undergoes drastic morphological changes during lactation to support breast milk production. A specific structure in fat cells called Connexin43 gap junctions (Cx43 GJs) plays an important role in facilitating intercellular communication in adipose tissue however, whether Cx43 GJs are vital in adipose tissue remolding and breast milk production is unknown. Research scientists in Houston, Texas, measured breast milk production and quantify macronutrients in breast milk from mice lacking the Cx43 GJs. They found that mothers lacking the functional adipocyte Cx43 GJs produced breast milk with reduced levels of lactose, a vital sugar found in milk that is important for supporting neonatal growth. Because many food components can modify adipose tissue Cx43 GJs levels, these data may support the idea of altering the lactating mother's diet to increase adipocyte Cx43 GJs.
Review Publications
Zhang, Z., Funcke, J., Zi, Z., Zhao, S., Straub, L.G., Zhu, Y., Zhu, Q., Crewe, C., An, Y.A., Chen, S., Li, N., Wang, M., Ghaben, A.L., Lee, C., Gautron, L., Engelking, L.J., Raj, P., Deng, Y., Gordillo, R., Kusminski, C.M., Scherer, P.E. 2021. Adipocyte iron levels impinge on a fat-gut crosstalk to regulate intestinal lipid absorption and mediate protection from obesity. Cell Metabolism. 33:1-16. https://doi.org/10.1016/j.cmet.2021.06.001.
Parkman, H.P., Sharkey, E., McCallum, R.W., Hasler, W.L., Koch, K.L., Sarosiek, I., Abell, T.L., Kuo, B., Shulman, R.J., Grover, M., Farrugia, G., Schey, R., Tonascia, J., Hamilton, F., Pasricha, P.J. 2020. Constipation in patients with symptoms of gastroparesis: Analysis of symptoms and gastrointestinal transit. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2020.10.045.
Parkman, H.P., Wilson, L.A., Yates, K.P., Koch, K.L., Abell, T.L., McCallum, R.W., Sarosiek, I., Kuo, B., Malik, Z., Schey, R., Shulman, R.J., Grover, M., Farrugia, G., Miriel, L., Tonascia, J., Hamilton, F., Pasricha, P.J., For the NIDDK/NIH Clinical Gastroparesis Consortium. 2021. Factors that contribute to the impairment of quality of life in gastroparesis. Neurogastroenterology & Motility. https://doi.org/10.1111/nmo.14087.
Chumpitazi, B.P., Palermo, T.M., Hollier, J.M., Self, M.M., Czyzewski, D., Weidler, E.M., Heitkemper, M., Shulman, R.J. 2021. Multisite pain is highly prevalent in children with functional abdominal pain disorders and is associated with increased morbidity. Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2021.04.059
Shulman, R.J., Devaraj, S., Heitkemper, M. 2020. Activation of the innate immune system in children with irritable bowel syndrome evidenced by increased fecal human B-defensin-2. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2020.09.034.
Pasricha, P.J., Grover, M., Yates, K.P., Abell, T.L., Bernard, C.E., Koch, K.L., McCallum, R.W., Sarosiek, I., Kuo, B., Bulat, R., Chen, J., Shulman, R.J., Lee, L., Tonascia, J., Miriel, L.A., Hamilton, F., Farrugia, G., Parkman, H.P. 2021. Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features Gastroenterology. 160(6):2006-2017. https://doi.org/10.1053/j.gastro.2021.01.230
Wolfson, S., Wilhelm, Z., Opekun, A.R., Orth, R., Shulman, R.J., Chumpitazi, B.P. 2021. Clinical characterization of pediatric gastroparesis using a four-hour gastric emptying scintigraphy standard. Journal of Pediatric Gastroenterology and Nutrition. 72(6): 848-853. https://doi.org/10.1097/MPG.0000000000003089.
Febo-Rodriguez, L., Chumpitazi, B.P., Musaad, S., Sher, A.C., Shulman, R.J. 2021. Meal induced symptoms in children with dyspepsia-Relationships to sex and the presence of gastroparesis. Journal of Pediatrics. 231:117-123. https://doi.org/10.1016/j.jpeds.2020.12.048.
Li, N., Zhao, S., Zhang, Z., Zhu, Y., Gliniak, C.M., Vishvanath, L., An, Y.A., Wang, M., Deng, Y., Zhu, Q., Shan, B., Sherwood, A., Onodera, T., Oz, O.K., Dixit, V.D., Scherer, P.E. 2021. Adiponectin preserves metabolic fitness during aging. eLife. 10:e65108. https://doi.org/10.7554/eLife.65108.
Wang, M., Dean, D.E., Quittner-Strom, E., Zhu, Y., Chowdhury, K.H., Zhang, Z., Zhao, S., Li, N., Ye, R., Lee, Y., Zhang, Y., Chen, S., Yu, X., Leonard, D.C., Poffenberger, G., Deylen, A.V., McCorkle, S.K., Schlegel, A., Sloop, K.W., Efanov, A.M., Gimeno, R.E., Scherer, P.E., Powers, A.C., Unger, R.H., Holland, W.L. 2021. Glucagon blockade restores functional B-cell mass in type 1 diabetic mice and enhances function of human islets. Proceedings of the National Academy of Sciences(PNAS). 118(9):e2022142118. https://doi.org/10.1073/pnas.2022142118.
Huang, M., Mathew, N., Zhu, Y. 2020. Assessing whole-body lipid-handling capacity in mice. The Journal of Visualized Experiments (JoVE). 165:e61927. https://doi.org/10.3791/61927.
Thapa, S., Venkatachalam, A., Khan, N., Naqvi, M., Balderas, M., Runge, J.K., Haag, A., Hoch, K.M., Glaze, D.G., Luna, R.A., Motil, K.J. 2021. Assessment of the gut bacterial microbiome and metabolome of girls and women with Rett Syndrome. PLoS ONE. 16(5):e0251231. https://doi.org/10.1371/journal.pone.0251231.
Singh, A., Ghosh, S., Ward, H., Manary, M.J., Rogers, B.L., Rosenberg, I.H. 2021. Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone. American Journal of Clinical Nutrition. 113:1556-1564. https://doi.org/10.1093/ajcn/nqaa434.
Griswold, S.P., Langlois, B.K., Shen, Y., Cliffer, I.R., Suri, D.J., Walton, S., Chui, K., Rosenberg, I.H., Koroma, A.S., Wegner, D., Hassan, A., Manary, M.J., Vosti, S.A., Webb, P., Rogers, B.L. 2021. Effectiveness and cost-effectiveness of 4 supplementary foods for treating moderate acute malnutrition: Results from a cluster-randomized intervention trial in Sierra Leone. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqab140.
Lelijveld, N., Godbout, C., Krietemeyer, D., Los, A., Wegner, D., Hendrixson, D.T., Bandsma, R., Koroma, A., Manary, M. 2021. Treating high-risk moderate acute malnutrition using therapeutic food compared with nutrition counseling (Hi-MAM Study): A cluster-randomized controlled trial. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqab137.
Bierut, T., Duckworth, L., Grabowsky, M., Ordiz, M., Laury, M.L., Callaghan-Gillespie, M., Maleta, K., Manary, M.J. 2020. The effect of bovine colostrum/egg supplementation compared with corn/soy flour in young Malawian children: A randomized, controlled clinical trial. American Journal of Clinical Nutrition. 113(2):420-427. https://academic.oup.com/ajcn/article/113/2/420/6040576.
Stephenson, K.B., Agapova, S.E., Hendrixson, D., Koroma, A., Manary, M.J. 2021. An optimized dose of therapeutic feeding results in noninferior growth in midupper arm circumference compared with a standard dose in children in Sierra Leone recovering from acute malnutrition. Current Developments in Nutrition. 5(2):nzab007. https://doi.org/10.1093/cdn/nzab007.
Chen, D., McKune, S.L., Singh, N., Yousuf Hassen, J., Gebreyes, W., Manary, M.J., Bardosh, K., Yang, Y., Diaz, N., Mohammed, A., Terefe, Y., Roba, K.T., Ketema, M., Ameha, N., Assefa, N., Rajashekara, G., Deblais, L., Ghanem, M., Yimer, G., Havelaar, A.H. 2021. Campylobacter colonization, environmental enteric dysfunction stunting, and associated risk factors among young children in rural Ethiopia: A cross-sectional study from the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) project. Frontiers in Public Health. 8:615793. https://doi.org/10.3389/fpubh.2020.615793.
Baranowski, T., Motil, K.J. 2021. Simple energy balance or microbiome for childhood obesity prevention? Nutrients. 13(8):2730. https://doi.org/10.3390/nu13082730.
Roediger, R., Hendrixson, D., Manary, M.J. 2020. A roadmap to reduce stunting. American Journal of Clinical Nutrition. 112(2):773S-776S. https://doi.org/10.1093/ajcn/nqaa205.
Schaefer, R., Mayberry, A., Briend, A., Manary, M., Walker, P., Stobaugh, H., Hanson, K., McGrath, M., Black, R. 2021. Relapse and regression to severe wasting in children under 5 years: A theoretical framework. Maternal and Child Nutrition. 17:e13107. https://doi.org/10.1111/mcn.13107.
Sorkin, J.D., Manary, M., Smeets, P.A., MacFarlane, A.J., Astrup, A., Duggan, C.P., Hogans, B.B., Odle, J., Davis, T.A., Tucker, K.L. 2021. A guide for authors and readers of the American Society for Nutrition Journals on the proper use of P values and strategies that promote transparency and improve research reproducibility. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqab223.
Chumpitazi, B.P., Hoffman, K.L., Smith, D.P., McMeans, A.R., Musaad, S., Versalovic, J., Petrosino, J.F., Shulman, R.J. 2021. Fructan-sensitive children with irritable bowel syndrome have distinct gut microbiome signatures. Alimentary Pharmacology & Therapeutics. 53:499-509.
