USDA Western Human Nutrition Research Center (WHNRC) Cross-Sectional Nutritional Phenotyping Study
Condition: Obesity; Inflammation
MeSH terms: Inflammation
Study type: Observational

Summary: 
      Although the diet of the US population meets or exceeds recommended intake levels of most
      essential nutrients, the quality of the diet consumed by many Americans is sub-optimal due to
      excessive intake of added sugars, solid fats, refined grains, and sodium. The foundations and
      outcomes of healthy vs. unhealthy eating habits and activity levels are complex and involve
      interactions between the environment and innate physiologic/genetic background. For instance,
      emerging research implicates chronic and acute stress responses and perturbations in the
      Hypothalamic-Pituitary-Adrenal axis in triggering obesity-promoting metabolic changes and
      poor food choices. In addition, the development of many chronic diseases, including
      cardiovascular disease, diabetes, cancer, asthma and autoimmune disease, results from an
      overactive immune response to host tissue or environmental antigens (e.g. inhaled allergens).
      A greater understanding is needed of the distribution of key environment-physiology
      interactions that drive overconsumption, create positive energy balance, and put health at
      risk.

      Researchers from the United States Department of Agriculture (USDA) Western Human Nutrition
      Research Center are conducting a cross-sectional "metabolic phenotyping" study of healthy
      people in the general population. Observational measurements include the interactions of
      habitual diet with the metabolic response to food intake, production of key hormones, the
      conversion of food into energy: the metabolism of fats, proteins, and carbohydrates,
      characteristics of the immune system, stress response, gut microbiota (bacteria in the
      intestinal tract), and cardiovascular health. Most outcomes will be measured in response to a
      mixed macronutrient/high fat challenge meal.
    

Detailed description: 
      Many inflammatory responses can be modulated by specific dietary components. For example, in
      cardiovascular disease, macrophages and T-cells react with oxidized LDL (an endogenous
      modified antigen) to produce arterial plaque and subsequent blockage of coronary arteries.
      High intake of saturated fats (or simple sugars that drive synthesis of saturated fatty
      acids) may promote this inflammation by affecting macrophages and T-cells. Conversely,
      increased intake of omega-3 fatty acids may decrease inflammation by suppression of
      macrophage and T-cell pro-inflammatory activity. Long-term sub-clinical inflammation caused
      by intestinal bacteria has been linked to the development of Irritable Bowel Disease and
      related disorders. Low intake of fruits, vegetables, or whole grains or high intake of
      saturated fats may promote sub-clinical gut inflammation by promoting dysbiosis of the gut
      microbiota. Allergic asthma develops in predisposed individuals as a result of an overactive
      allergic-type immune response to inhaled environmental allergens. Dietary factors such as
      vitamin D and omega-3 fatty acids may diminish pro-inflammatory responses to environmental
      allergens by promoting the development of T-regulatory cells and other anti-inflammatory
      factors.

      Individual variability in chronic disease risk is well recognized. For example, why does
      excess adiposity lead to disease in some individuals and not others? The nature of the fat
      tissue rather than the abundance, may impact cross-talk with other metabolically-relevant
      tissues and affect disease risk. It is important to characterize healthy vs. unhealthy
      phenotypes across various tissues and to understand how micro- and macro-nutrients interact
      with molecular and metabolic pathways to support a healthy body weight. This study brings
      together scientists with expertise in nutritional sciences, immunology, analytical chemistry,
      physiology, neuroendocrinology, and behavior to understand how diet impacts metabolism and
      disease risk through the interplay and coordination of signals and metabolites arising from
      multiple organ systems.

      The overall objective is to characterize the phenotypic profile of participants according to
      their immunologic, physiologic, neuroendocrine, and metabolic responses to a dietary
      challenge and a physical fitness challenge by addressing the specific aims listed below. The
      cross-sectional study is organized into two study visits (Visit 1 and Visit 2) separated by
      approximately two weeks of at-home specimen and data collection.

      Specific Aim 1: To determine if diet quality is independently associated with systemic immune
      activation, inflammation, or oxidative stress differentiated by:

        1. pro-inflammatory T-helper cells (Th1, Th2, and Th17 cells) and related cytokines

        2. anti-inflammatory T-regulatory cells and related cytokines

        3. dysbiosis of the gut microbiota and markers of gut inflammation (e.g. neopterin and
           myeloperoxidase)

           a. and to evaluate the association between dysbiosis of the gut microbiota, gut
           inflammation, and systemic immune activation

        4. plasma metabolomic response to a mixed macronutrient challenge meal (includes diet
           quality and physical activity as independent variables)

        5. endothelial (dys)function and vascular reactivity

      Specific Aim 2: To determine if a high fat/sugar challenge meal induces differential effects
      over time (0-6h postprandial) according to habitual diet characteristics, physical activity
      levels, stress levels, age, sex, or BMI on:

        1. postprandial monocyte activation

        2. plasma lipid metabolomic responses including non-esterified fatty acids, phospholipids,
           triacylglycerols, red blood cell fatty acids, endocannabinoids, bile acids, eicosanoids
           and related oxylipins, ceramides, sphingoid bases, and acylcarnitines

        3. plasma amino acid metabolomics

        4. glucose metabolism and metabolic flexibility (i.e. the ability to switch from glucose to
           lipid oxidation as energy sources)

        5. changes in endocrinology and self-report of hunger and satiety

        6. postprandial free cortisol

      Specific Aim 3: To determine the mechanisms of:

        1. postprandial monocyte activation

        2. suppression of challenge-meal induced monocyte activation by docosahexaenoic acid (DHA)
           (in an ex vivo experiment using a subset of samples)

      Specific Aim 4: To evaluate the associations between eating behavior, physical activity,
      and/or anthropometry and the outcomes:

        1. endocrinology of hunger and satiety

        2. plasma metabolomic responses

        3. vulnerability and resistance to stress

        4. endothelial (dys)function and vascular reactivity

        5. prediction of insulin sensitivity

      Specific Aim 5: To determine how genetic variants affect nutrient metabolism, cardiovascular
      physiology, and immune function and improve understanding of how dietary factors affect these
      metabolic, cardiovascular and immune phenotypes.
    

Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Healthy people in the general population
      
Biospecimen description: 
      Whole blood, stool
    
Keywords: Diet; Phenotype; Immunology; Microbiota; Metabolomics; Physical activity; Neuroendocrine system; Nutritional Physiological Phenomena