Research Project: Nutritional Role of Phytochemicals

Location: Children's Nutrition Research Center

2022 Annual Report

Objectives
The overall goal of our research is to better understand the impact of specific components of plant-based foods have on nutritional health and dietary outcomes. Research will be undertaken that aims to increase our understanding of the negative impact of dietary oxalic acid on human health and the mechanisms regulating its concentration in plant foods. Additionally we aim to increase our understanding of the role of carotenoids to improve the health and quality of life for mothers and infants. To accomplish this the following objectives will be undertaken: 1) characterize oxalate catabolic activity in low and high oxalate plants of dietary importance such as leafy greens harvested at different stages of development; 2) identify and characterize in a model plant system the genes and encoded proteins responsible for each step in a novel pathway of oxalate catabolism; 3) determine the influence of the newly identified oxalate catabolism pathway on the nutritional composition, phytochemical profile, and production characteristics in plants of dietary importance such as leafy greens grown to different stages of maturity (microgreens to mature greens); 4) to define the effect of pregnancy and lactation on carotenoid and vitamin A status and markers of bioactivity in diverse healthy weight and obese women; 5) to determine the pharmacokinetic basis for why adiposity affects breast milk carotenoid composition; 6) determine the interaction between antinutrients calcium oxalate and phytate in plant foods and the gut microbiome; and to 7)utilize a germ-free murine model to determine the inter-relationships between microbial gut ecology, plant calcium oxalate content or phytate content and host calcium, zinc and iron bioavailability.

Approach
These research studies will use various techniques to accomplish the research to be undertaken. We will assess the oxalate catabolic activity in low and high oxalate plants of dietary importance at different stages of development. Various analyses will be utilized (mineral, bioavailability, statistical and microscopic analysis of calcium oxalate crystal deposition) to address these research objectives. Further, carotenoid and vitamin A status of the mother during pregnancy and lactation are important to assure optimal health of the mother and adequate transfer of these components to the fetus and infant, respectively. A quasi-experimental (observational) study of a diverse group of U.S. mothers during pregnancy and early lactation will be conducted to define the key determinants of changes in carotenoid and vitamin A status across pregnancy and to explore the implications of these changes for markers of inflammation and cognitive function. Researchers will also examine the nutritional composition of food and explore how these components regulate metabolism. Mice fed plant diets differing in antinutrient content along with in vitro phenotyping will provide insight into the impact of antinutrients on microbial composition. Mice colonized with microbiomes associated with either an antinutrient replete or antinutrient deficient plant-based diet will be used in feeding studies to address alterations in Ca, Zn, and Fe absorption.

Progress Report
To review the progress made during the year, please refer to the following projects: 3092-51000-063-01S (Project #1), 3092-51000-063-02S (Project #2), and 3092-51000-063-03S (Project #3).

Accomplishments
1. An enzyme important for oxalate breakdown is conserved in plants. Plant scientists have been avidly working to discover new strategies to reduce oxalate in plant foods. Oxalate inhibits the consumer's ability to absorb the calcium present in plant foods and can contribute to kidney stone formation (>75% of all kidney stones contain oxalate as a primary component). Additionally, certain plant pathogens produce oxalate as a requirement for infection and these oxalate-secreting pathogens are responsible for more than $100M in crop losses annually; therefore, reducing oxalate through degradation can improve the nutritional quality and production of plant foods. ARS scientists in Houston, Texas, discovered that oxalyl-CoA decarboxylase is the enzyme responsible for the second step in a previously uncharacterized pathway of oxalate break down in Arabidopsis. The researchers also found that this enzyme is present in other crop plants such as rice, maize, spinach, and tomato. These findings suggests that this enzyme and pathway of oxalate break down may be an avenue that will lead to the development of new strategies to improve the nutrition quality of plant foods and the resistance of plants against infection from certain oxalate-secreting fungal pathogens.

Review Publications
Moran, N.E., Thomas-Ahner, J.M., Smith, J.W., Silva, C., Hason, N.A., Erdman, J.W., Clinton, S.K. 2021. Beta-carotene oxygenase 2 genotype modulates the impact of dietary lycopene on gene expression during early TRAMP prostate carcinogenesis. Journal of Nutrition. 152(4):950-960. https://doi.org/10.1093/jn/nxab445.
Zaidi, Y., Moran, N.E., Stroh, R. 2022. Systematic review of carotenoid concentrations in human milk and infant blood. Nutrition Reviews. https://doi.org/10.1093/nutrit/nuac018.
Moran, N.E., Thomas-Ahner, J.M., Wan, L., Zuniga, K.E., Erdman, J.W., Clinton, S.K. 2022. Tomatoes, lycopene, and prostate cancer: What have we learned from experimental models? Journal of Nutrition. https://doi.org/10.1093/jn/nxac066.
Cheng, N., Paris, V., Rao, X., Wang, X., Nakata, P.A. 2022. A conserved oxalyl-coenzyme A decarboxylase in oxalate catabolism. Plant Signaling and Behavior. 17:1. https://doi.org/10.1080/15592324.2022.2062555.
Jilcott Pitts, S.B., Moran, N.E., Wu, Q., Harnack, L., Craft, N.E., Hanchard, N., Bell, R., Moe, S.G., Johnson, N., Obasohan, J., Carr-Manthe, P.L., Laska, M.N. 2021. Pressure-mediated reflection spectroscopy criterion validity as a biomarker of fruit and vegetable intake: A two-side cross-sectional study of four racial or ethnic groups. Journal of Nutrition. https://doi.org/10.1093/jn/nxab349.
Radtke, M.D., Poe, M., Stookey, J., Jilcott Pitts, S., Moran, N.E., Landry, M.J., Rubin, L.P., Scherr, R.E. 2021. Recommendations for the use of the veggie meter for spectroscopy-based skin carotenoid measurements in the research setting. Current Developments in Nutrition. 5(8). Article nzab104. https://doi.org/10.1093/cdn/nzab104.
Dzakovich, M.P., Francis, D.M., Cooperstone, J.L. 2022. Steroidal alkaloid biosynthesis is coordinately regulated and differs among tomatoes in the red-fruited clade. The Plant Genome. https://doi.org/10.1002/tpg2.20192.
Chumpitazi, C.E., Camp, E.A., Cuevas-Guaman, M., Doughty, C., Kancherla, B., Lingappan, K., Moran, N.E., Murray, K.O., Perez, O., Shekerdemian, L.S., O'Connor, T.M. 2022. Vision 2020: How caregiving and work productivity outlook shifted for academic pediatric faculty. Journal of Women's Health. https://doi.org/10.1089/jwh.2021.0555.
Sprague, S.A., Tamang, T., Steiner, T., Wu, Q., Hu, Y., Kakeshpour, T., Park, J., Yang, J., Peng, Z., Bergkamp, B., Somayanda, I., Peterson, M., Garcia, E., Hao, Y., Amand, P., Bai, G., Nakata, P.A., Rieu, I., Jackson, D.P., Cheng, N., Valent, B., Hirschi, K.D., Jagadish, S., Liu, S., White, F.F., Park, S. 2022. Redox-engineering enhances maize thermotolerance and grain yield in the field. Plant Biotechnology. https://doi.org/10.1111/pbi.13866.
Grainger, E.M., Webb, M.Z., Simpson, C.M., Chitchumroonchokchai, C., Riedl, K., Moran, N.E., Clinton, S.K. 2022. Assessment of dietary carotenoid intake and biologic measurement of exposure in humans. In: Wurtzel, E.T. editor. Methods in Enzymology. 1st edition. Cambridge, MA: Academic Press. p. 255-295. https://doi.org/10.1016/bs.mie.2022.05.007.
Moran, N.E., Chang, J., Stroh, R., Zaidi, Y., Hason, N., Musaad, S., O'Connor, T. 2022. Non-invasive, reflection spectroscopy measurement of skin carotenoid score in infants is feasible and reliable. Journal of Nutrition. https://doi.org/10.1093/jn/nxac182 .