Location: Children's Nutrition Research Center
2024 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: 3092-10700-067-10S (Project #1), 3092-10700-067-30S (Project #2), and 3092-10700-067-40S (Project #3).
Accomplishments
1. Boys and girls have different reactions to dietary fiber. Americans consume far less fiber than recommended and it is unclear if fiber is beneficial to specific individuals more so than others. To confirm our previous finding that increasing dietary fiber intake reduced the amount of belly pain in boys but not girls, researchers at the Children’s Nutrition Research Center in Houston, Texas, evaluated the dietary fiber intake in healthy children and those who often had belly pain. We found that in healthy boys and those with frequent belly pain, the more dietary fiber consumed, the less pain the boys had while in contrast, in healthy girls and those with frequent belly pain, there was no relationship between the amount of dietary fiber intake and belly pain. When we examined only children with frequent belly pain, boys who ate more than the recommended amount of dietary fiber had less belly pain than those who did not eat at least the recommended amount. In contrast, in girls with belly pain, those who ate more than the recommended amount of dietary fiber had more belly pain than the girls who ate less than the recommended amount. These novel findings highlight the importance of sex in response to dietary nutrients such as fiber and the need for additional studies to understand what factors underlie these sex differences.
2. A reliable measurement for cowpea consumption is possible. Legumes, particularly cowpeas, are indigenous crops in sub-Saharan Africa and contain larger quantities of protein than cereals but at present, there is no reliable, convenient way to determine the quantity of cowpea, to combat childhood malnutrition and growth faltering. This limits the ability of researchers to assess the effectiveness of activities that promote legume consumption as well as compliance to nutritional education efforts. Researchers associated with the Children's Nutrition Research Center in Houston, Texas, aimed to identify a suite of metabolic consumption biomarkers by collecting and analyzing urine and dried blood spots from children and pregnant women in Northern Ghana that consumed four cowpea varieties. Ten candidate biomarkers were identified for cowpea consumption which included phytochemicals unique to plants and other biomarkers that tell us the effect of cowpea in human metabolism and provides insight into how cowpeas enhance human nutrition. These results support a suite of key metabolites for dietary legume and cowpea-specific food exposure of global health importance and will permit a reliable measure of cowpea consumption in the future.
3. Maternal metabolic adaptation during lactation. Energy needs are maintained during pregnancy; however, birth is associated with a dramatic shift to a net negative energy balance for the mother during lactation. Our knowledge for how the maternal metabolome adapts to lactation is limited, therefore the careful study of regulatory mechanisms that occur during lactation provide valuable insights into metabolic flexibility, sustaining healthy nutrition for the mother and offspring, and potential long-term metabolic benefits for the mother. Researchers at the Children’s Nutrition Research Center in Houston, Texas, studied regulatory circuits that control nutritional and metabolic homeostasis in mice at peak lactation (maximal milk production) and identified altered regulation of lipid and glucose metabolism, supporting the concept that metabolic adaptations occur during lactation and identify potential long-term metabolic consequences that result from lactation. These studies are important because they support the development of future therapies aimed to improve lactation efficiency as well as identify new candidates for management of metabolic diseases.
Review Publications
Wooton-Kee, C. 2023. Therapeutic implications of impaired nuclear receptor function and dysregulated metabolism in Wilson's disease. Pharmacology and Therapeutics. 251. Article 108529. https://doi.org/10.1016/j.pharmthera.2023.108529.
Hollier, J.M., Strickland, T.A., Fordis, C.M., Shulman, R.J., Thompson, D.J. 2024. Expert review of child and caregiver critiques of a therapeutic guided imagery therapy mobile application targeting disorders of gut-brain interaction in children. Digital Health. https://doi.org/10.1177/20552076241245376.
Kaul, I., Burton-Murray, H., Musaad, S., Mirabile, Y., Czyzewski, D., Van Tilburg, M.A., Sher, A.C., Chumpitazi, B.P., Shulman, R.J. 2024. Avoidant/restrictive food intake disorder prevalence is high in children with gastroparesis and functional dyspepsia. Neurogastroenterology & Motility. 36(5). Article e14777. https://doi.org/10.1111/nmo.14777.
So, S., Badu, S., Wu, Q., Yalcinkaya, N., Mirabile, Y., Castaneda, R., Musaad, S., Heitkemper, M., Savidge, T.C., Shulman, R.J. 2023. Sex-dependent efficacy of dietary fiber in pediatric functional abdominal pain. Gastroenterology. 166(4):645-657. https://doi.org/10.1053/j.gastro.2023.12.011.
Chikkamenahalli, L.L., Jessen, E., Bernard, C.E., Ip, W., Breen-Lyles, M., Cipriani, G., Pullapantula, S.R., Li, Y., Alasfoor, S., Wilson, L., Koch, K.L., Kuo, B., Shulman, R.J., Chumpitazi, B.P., McKenzie, T.J., Kellogg, T.A., Tonascia, J., Hamilton, F.A., Sarosiek, I., McCallum, R., Parkman, H.P., Pasricha, P.J., Abell, T.L., Farrugia, G., Dasari, S., Grover, M. 2024. Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis. iScience. 27(3). Article 108991. https://doi.org/10.1016/j.isci.2024.108991.
Parkman, H.P., Wilson, L.A., Silver, P., Maurer, A.H., Sarosiek, I., Bulat, R.S., Kuo, B., Grover, M., Farrugia, G., Chumpitazi, B.P., Shulman, R.J., Malik, Z., Miriel, L.A., Tonascia, J., Hamilton, F., Abell, T.L., Pasricha, P.J., McCallum, R.W., Koch, K.L. 2023. Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis. American Journal of Physiology - Gastrointestinal and Liver Physiology. 325(5):G407-417. https://doi.org/10.1152/ajpgi.00065.2023.
Mechlowitz, K., Singh, N., Li, X., Chen, D., Yang, Y., Rabil, A., Cheraso, A.J., Ahmed, I.A., Amin, J.K., Gebreyes, W.A., Hassen, J.Y., Ibrahim, A.M., Manary, M.J., Rajashekara, G., Roba, K.T., Usmane, I.A., Havelaar, A.H., McKune, S.L. 2023. Women's empowerment and child nutrition in a context of shifting livelihoods in Eastern Oromia, Ethiopia. Frontiers in Nutrition. 10. Article 1048532. https://doi.org/10.3389/fnut.2023.1048532.
Koroma, A.S., Gustafson, B., Kohlen, C., Moore, M., Ngegbai, S., Kleban, E., Wegner, D.R., Kidd, P., Stephenson, K.B., Li, Y.N., Brenna, J.T., Manary, M.J. 2024. Feasibility and acceptability of a supplementary food with added fish oil and choline for undernourished pregnant women in Sierra Leone. African Journal of Food, Agriculture, Nutrition and Development. 24(4):26072-26093. https://doi.org/10.18697/ajfand.129.24480.
Koroma, A.S., Stephenson, K.B., Iversen, P.O., Manary, M.J., Hendrixson, D.T. 2024. The effect of breastfeeding practices of undernourished mothers in rural Sierra Leone on infant growth and mortality. Children. 11(2). Article 233. https://doi.org/10.3390/children11020233.
Tu, L., Bean, J.C., He, Y., Liu, H., Yu, M., Liu, H., Zhang, N., Yin, N., Han, J., Scarcelli, N.A., Conde, K.M., Wang, M., Li, Y., Feng, B., Gao, P., Cai, Z., Fukuda, M., Xue, M., Tong, Q., Yang, Y., Liao, L., Xu, J., Wang, C., He, Y., Xu, Y. 2023. Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia. Journal of Clinical Investigation. 133(14). Article e163391. https://doi.org/10.1172/JCI163391.
Liu, H., Qu, N., Gonzalez, N., Palma, M.A., Chen, H., Xiong, J., Choubey, A., Li, Y., Li, X., Yu, M., Liu, H., Tu, L., Zhang, N., Yin, N., Conde, K.M., Wang, M., Bean, J., Han, J., Scarcelli, N.A., Yang, Y., Saito, K., Cui, H., Tong, Q., Sun, Z., Wang, C., He, Y., Xu, Y. 2024. A light-responsive neural circuit suppresses feeding. Journal of Neuroscience. 44(30). Article e2192232024. https://doi.org/10.1523/JNEUROSCI.2192-23.2024.
Li, Y., Cacciottolo, T.M., Yin, N., He, Y., Liu, H., Liu, H., Yang, Y., Henning, E., Keogh, J.M., Lawler, K., Mendes De Oliveira, E., Gardner, E.J., Kentistou, K.A., Laouris, P., Bounds, R., Ong, K.K., Perry, J.R., Barroso, I., Tu, L., Bean, J.C., Yu, M., Conde, K.M., Wang, M., Ginnard, O., Fang, X., Tong, L., Han, J., Darwich, T., Williams, K.W., Yang, Y., Wang, C., Joss, S., Firth, H.V., Xu, Y., Farooqi, I. 2024. Loss of transient receptor potential channel 5 causes obesity and postpartum depression. Cell. https://doi.org/10.1016/j.cell.2024.06.001.
Tavares, L.C., Zheng, T., Kwicklis, M., Mitchell, E., Pandit, A., Pullapantula, S., Bernard, C., Teder-Laving, M., Marques, F.Z., Esko, T., Kuo, B., Shulman, R.J., Chumpitazi, B.P., Koch, K.L., Sarosiek, I., Abell, T.L., McCallum, R.W., Parkman, H.P., Pasricha, P.J., Hamilton, F.A., Tonascia, J., Zawistowski, M., Farrugia, G., Grover, M., D'Amato, M. 2023. A pilot genome-wide association study meta-analysis of gastroparesis. United European Gastroenterology Journal. 11(8):784-796. https://doi.org/10.1002/ueg2.12453.
Tipton, M., Baxter, B.A., Pfluger, B.A., Sayre-Chavez, B., Muñoz-Amatriaín, M., Broeckling, C.D., Shani, I., Steiner-Asiedu, M., Manary, M., Ryan, E.P. 2024. Urine and dried blood spots from children and pregnant women reveal phytochemicals, amino acids, and carnitine metabolites as cowpea consumption biomarkers. Molecular Nutrition and Food Research. 68(4). Article e2300222. https://doi.org/10.1002/mnfr.202300222.
Fu, Y., Ding, B., Liu, X., Zhao, S., Chen, F., Li, L., Zhu, Y., Yuan, Z., Shen, Y., Yang, C., Zhao, J., Shao, M., Chen, S., Bickel, P.E., Zhong, Q. 2023. Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B. Cell Discovery. 9. Article 115. https://doi.org/10.1038/s41421-023-00613-4.
Zhao, S., Lin, Q., Xiong, W., Li, L., Straub, L., Zhang, D., Zapata, R., Zhu, Q., Sun, X., Zhang, Z., Funcke, J., Li, C., Chen, S., Zhu, Y., Jiang, N., Li, G., Xu, Z., Wyler, S.C., Wang, M., Juli, B., Han, X., Kusminski, C.M., Zhang, Z., An, Z., Elmquist, J.K., Osborn, O., Liu, C., Scherer, P.E. 2023. Hyperleptinemia contributes to antipsychotic drug–associated obesity and metabolic disorders. Science Translational Medicine. 15. Article 723. https://doi.org/10.1126/scitranslmed.ade8460.
Zhao, S., Li, N., Xiong, W., Li, G., He, S., Zhang, Z., Zhu, Q., Jiang, N., Ikejiofor, C., Zhu, Y., Wang, M., Han, X., Zhang, N., Solis-Herrera, C., Kusminski, C., An, Z., Elmquist, J.K., Scherer, P.E. 2024. Leptin reduction as a required component for weight loss. Diabetes. 73(2):197-210. https://doi.org/10.2337/db23-0571.
Chen, X., Li, H., Liu, Y., Qi, J., Dong, B., Huang, S., Zhao, S., Zhu, Y. 2023. Dimethyl sulfoxide inhibits bile acid synthesis in healthy mice but does not protect mice from bile-acid-induced liver damage. Biology. 12(8). Article 1105. https://doi.org/10.3390/biology12081105.
Liu, H., He, Y., Liu, H., Brouwers, B., Yin, N., Lawler, K., Keogh, J.M., Henning, E., Lee, D., Yu, M., Tu, L., Zhang, N., Conde, K.M., Han, J., Yan, Z., Scarcelli, N.A., Liao, L., Xu, J., Tong, Q., Zheng, H., Sun, Z., Yang, Y., Wang, C., He, Y., Farooqi, I., Xu, Y. 2024. Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans. Science Advances. https://doi.org/10.1126/sciadv.adl2675.