Assessing the Impact of Diet on Inflammation in Healthy and Obese Adults in a Cross-Sectional Phenotyping Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 393
- 试验地点
- 1
- 主要终点
- Baseline level and change in systemic immune activation following challenge meal
研究概览
简要总结
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.
详细描述
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:
- pro-inflammatory T-helper cells (Th1, Th2, and Th17 cells) and related cytokines
- anti-inflammatory T-regulatory cells and related cytokines
- dysbiosis of the gut microbiota and markers of gut inflammation (e.g. neopterin and myeloperoxidase)
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female
- •Body Mass Index 18.5-45.0 kg/m2 (Normal to obese)
排除标准
- •Pregnant or lactating women
- •Known allergy to egg-white protein
- •Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg measured on three separate occasions
- •Diagnosed active chronic diseases for which the individual is currently taking daily medication, including but not limited to:
- •Diabetes mellitus
- •Cardiovascular disease
- •Gastrointestinal disorders
- •Kidney disease
- •Liver disease
- •Bleeding disorders
- •Autoimmune disorders
- •Hypertension
- •Osteoporosis
- •Recent minor surgery (within 4 wk) or major surgery (within 16 wk)
- •Recent antibiotic therapy (within 4 wk)
- •Recent hospitalization (within 4 wk)
- •Use of prescription medications at the time of the study that directly affect endpoints of interest (e.g. hyperlipidemia, glycemic control, steroids, statins, anti-inflammatory agents, and over-the-counter weight loss aids)
研究组 & 干预措施
Sampling strata
Stratified analyses of primary and secondary outcomes based on variables of interest (e.g. sex, age, or BMI) may occur prior to achieving the target for total study enrollment.
结局指标
主要结局
Baseline level and change in systemic immune activation following challenge meal
时间窗: 0, 0.5, 3, and 6 hours postprandial
Number and activation level of pro-inflammatory T-helper (Th) cells (Th1, Th2 and Th17), T-regulatory (Treg) cells, and B cells will be measured in fasting blood. Monocytes and neutrophils will be measured in fasting and postprandial blood.
Baseline level and change in plasma metabolome
时间窗: 0, 0.5, 3, and 6 hours postprandial
Plasma fatty acid profiles of non-esterified fatty acids, phospholipids, triacylglycerols, red blood cell fatty acids, endocannabinoids, bile acids, eicosanoids and related oxylipins, ceramides, sphingoid bases, acylcarnitines, amino acids and other metabolites measured in response to a challenge meal.
次要结局
- Baseline level and change in appetitive hormones(0, 0.5, 3, and 6 hours postprandial)
- Resting and change in metabolism(0, 0.5, 3, and 6 hours postprandial)
- Vital signs(single time point)
- Body composition(single time point)
- Baseline and change in hunger and appetite(0, 1, 2, 3, 4, 5, and 6 hours postprandial)
- Usual physical activity(single time point)
- Baseline level and change in glucose metabolism(0, 0.5, 3, and 6 hours postprandial)
- Baseline level and change in mitogen activated protein (MAP) kinase activity(0, 0.5, 3 and 6 hours postprandial)
- Genome Wide Association Study (GWAS)(0 hours (fasting))
- Recent dietary intake(Three 24-hour dietary recalls collected at home)
- Taste thresholds(single time point)
- Executive function(single time point)
- Submaximal oxygen consumption(single time point)
- Aerobic fitness assessment(single time point)
- Baseline level and change in dietary-responsive, circulating microRNA(0, 0.5, 3, and 6 hours postprandial)
- Baseline level and change in RNA transcriptome(0, 3, and 6 hours postprandial)
- General health(0 hours (Fasting))
- Anthropometrics(single time point)
- Stool RNA markers(single time point)
- Baseline and change in gut fermentation profile(0, 1, 2, 3, 4, 5, and 6 hours postprandial)
- Behavior assessment(single time point)
- Peripheral arterial tone(single time point)
- Pulmonary inflammation(single time point)
- Cognitive function(single time point)
- Allostatic Load(single time point)
- Baseline and change in salivary cortisol in response to exercise(0, immediately post-exercise, 30, 60, and 90 minutes post-exercise)
- Gut microbiota(single time point)
- Gut inflammation(single time point)
- Stool metabolites(single time point)
- Heart rate variability and autonomic nerve conductivity(single time point)
- Gut microbiota fermentation capacity(single time point)
- Gut microbiota pathogen resistance capacity(single time point)
- Dietary intake(single time point)
- Skin reflectance(single time point)
- Pulmonary function(single time point)
- Physical activity(daily, for 7 days)
- Baseline and change in salivary cortisol in response to test meal(0, immediately post-prandial, 30, 60, and 90 minutes post-prandial)
- Baseline and change in salivary cortisol in response to emotional recall task(0, immediately post-task, 30, 60, and 90 minutes post-task)
- Baseline and change in breath aldehydes(0, 1, 4 and 6 hours postprandial)