My research program focuses on evaluating endotypes of nutrition-related diseases, with the long-term goals of identifying earlier and subclinical indicators of pathogenesis to improve prevention efforts. Nutrition-related diseases of interest include metabolic abnormalities and diseases such as diabetes and infectious diseases. Key questions of interest are centered around three themes: 1) metabolic health and homeostasis; 2) novel biomarkers of nutrition-related diseases; and 3) diverse clinical manifestations of nutrition-related diseases. My epidemiologic approach is centered around blood biomarkers, including high-resolution metabolomic data, in translational and precision health studies. Previous and future study populations of interest include people considered higher risk, particularly those residing in resource-limited environments or with medical conditions requiring blood transfusions, and blood donors.
Metabolic health and homeostasis
To what extent can novel dynamic indicators of metabolic processes, such as postprandial metabolic flexibility, improve the prediction of nutrition-related disease risk? What specific definitions of metabolic flexibility and homeostasis are relevant for maintaining metabolic health and preventing metabolic diseases?
Metabolic health remains incompletely understood; this key underlying research gap is a major obstacle to reducing the growing global burden of disease from metabolic diseases and high body mass index. Metabolic flexibility is essential for energy homeostasis and maintenance of metabolic health. Broadly, metabolic flexibility is defined as the body’s ability to appropriately respond to physiologic challenges allows for homeostatic regulation during meals, exercise, and rest. With Dr. Aryeh Stein (Emory University), we evaluated postprandial metabolic flexibility through comparing high-resolution non-targeted metabolomic profiles at two hours after consuming a standardized meal challenge, relative to while fasting [1, 2, 3]. Energy, macronutrient, and bile acid metabolism pathways were responsive to the meal challenge among healthy individuals . Compared to the postprandial response between adults with versus without cardiometabolic diseases (hypertension, diabetes, metabolic syndrome, or obesity), those with cardiometabolic diseases showed a greater number of metabolomic features that were altered . Assuming that most observed metabolites are homeostatically regulated, this finding suggested lower metabolic flexibility among those with CMDs . Postprandial metabolomic profile response to a standardized meal challenge also differed based on fasting inflammation status .
1. Yu EA, Yu T, Jones DP, Martorell R, Ramirez-Zea M, Stein AD. Macronutrient, Energy, and Bile Acid Metabolism Pathways Altered Following a Physiological Meal Challenge, Relative to Fasting, among Guatemalan Adults. J Nutr, 2020. 150(8): 2031-2040.
2. Yu EA, Yu T, Jones DP, Ramirez-Zea M, Stein AD. Metabolomic profiling after meal shows greater changes and lower metabolic flexibility in cardiometabolic diseases. J Endocr Soc, 2020. 4(11): 1-13.
3. Yu EA, Le NA, Stein AD. Measuring postprandial metabolic flexibility to assess metabolic health and disease. J Nutr, 2021. DOI: 10.1093/jn/nxab263. 151(11): 3284-3291.
4. Yu EA, He S, Jones DP, Sun YV, Ramirez-Zea M, Stein AD. Metabolomic profiling demonstrates postprandial changes in fatty acids and glycerophospholipids are associated with fasting inflammation in Guatemalan adults. J Nutr, 2021. DOI: 10.1093/jn/nxab183. 151(9):2564-2573.
Novel biomarkers of nutrition-related diseases
Are there key host factors (metabolites or metabolomic profiles, microbiome, nutritional status indicators) linked with infectious diseases? Could these provide earlier indicators prior to disease onset and of specific clinical phenotype subgroups?
Previously I evaluated the extent that novel immunological and microbiome indicators were associated with active TB disease. I found that in response to an ex vivo Mycobacterium tuberculosis challenge, peripheral blood mononuclear cells (PBMCs) from patients with active TB disease and latent TB infection had distinct transcriptional profiles, as compared to PBMCs of healthy controls . We also considered the human microbiome and micronutrient status, which could represent key modifiable host factors in active tuberculosis disease. In a systematic review, we found that prior evidence showed decreased gastrointestinal microbial diversity was associated with active tuberculosis disease and M. tb infection, though available data were very limited . In a pilot study among adults with active tuberculosis disease in India, low serum vitamin D concentration (< 75 nmol/L of 25[OH]D) was associated with the relative abundance of Oscillospira spp., which is a butyrate-producing genus associated with anti-inflammation (16S rRNA) .
1. Yu EA, Hu PJ, Mehta S. 2018. Plasma fatty acids in de novo lipogenesis pathway are associated with diabetogenic indicators among adults: NHANES 2003-2004. Am J Clin Nutr, 2018. 108: 622-632.
2. Huey SH,* Yu EA,* Finkelstein JL, Glesby MJ, Bonam W, Russell DG, Mehta S. Gut microbiota and micronutrient status differ by inflammation among outpatients with active tuberculosis disease in India. Am J Trop Med Hyg. In press.
3. Yu EA, John SH, Tablante EC, King CA, Kenneth J, Russell DG, Mehta S. Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status. PLoS One, 2017. 12(10): e0185640.
4. Wood MR,* Yu EA,* Mehta S. The Human Microbiome in the Fight Against Tuberculosis. Am J Trop Med Hyg, 2017. 96(6): 1274-1284.
* Authors contributed equally
Figure modified from DOI: 10.1371/journal.pone.0185640
Diverse clinical manifestations of nutrition-related diseases
Are there more effective, tailored approaches for preventing and treating diverse disease phenotypes and comorbidities observed in the epidemiological transition and dual burden of malnutrition?
My earlier work sought to elucidate the diabetes and active tuberculosis (TB) disease comorbidity, which has been observed among people residing in many low- and middle-income countries (with Dr. Saurabh Mehta at Cornell University). Among Indian patients with confirmed or suspected active TB disease, over 80% of adult participants had low BMI and waist circumference, which indicated low risk in diabetes screening ; however approximately one-third of these participants had elevated HbA1c (≥ 5.7%) . In a separate study of patients with confirmed active tuberculosis disease in southern India, diabetes was associated with a three-fold greater risk of drug (rifampin) resistance . These findings emphasized the need for integrated diabetes surveillance in TB programs, particularly in geographic regions undergoing the epidemiological transition.
1. Yu EA, Finkelstein JL, Brannon PM, Bonam W, Russell DG, Glesby MJ, Mehta S. Nutritional assessment among adult patients with suspected or confirmed active tuberculosis disease in rural India. PLoS One, 2020. 15(5): e0233306.
2. Mehta S, Yu EA, Ahamed SF, Bonam W, Kenneth J. Rifampin resistance and diabetes mellitus in a cross-sectional study of adult patients in rural South India. BMC Infect Dis, 2015. 15: 451.