Ultra-processed food consumption, gut microbiota, and glucose homeostasis in mid-life adults

中年成年人的超加工食品消费、肠道微生物群和葡萄糖稳态

• 批准号: 10618337
• 负责人: BRENDA M DAVY
• 金额: $ 24.53万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618337
• 关键词: Address; Adult; Adverse effects; Aging; Animal Experimentation; Antioxidants; Bacteria; Behavior; Beta Cell; Bile Acids; Body Weight Changes; Butyrates; Carbohydrates; Cardiovascular Diseases; Cell physiology; Chemicals; Chronic; Chronic Disease; Clinical; Consumption; Continuous Glucose Monitor; Diagnostic; Diet; Dietary Factors; Dietary Fiber; Dietary Intervention; Disease; Elderly; Endotoxins; Energy Intake; Event; Fatty acid glycerol esters; Food; Future; Grain; Impairment; Individual; Industrialization; Inflammation; Inflammatory; Insulin Resistance; Intake; Intervention Studies; Intestinal permeability; Lead; Life; Link; Measurement; Micronutrients; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Observational Study; Outcome Study; Participant; Physiological; Population; Prediabetes syndrome; Predisposition; Prevention Guidelines; Prevention Research; Prevention approach; Probiotics; Process; Processed Meats; Production; Proteins; Public Health; Randomized; Reducing diet; Reproducibility; Research; Risk; Risk Factors; Serum; Sodium; Vitamins; Volatile Fatty Acids; age related; aged; blood glucose regulation; cytokine; design; diabetes risk; dietary; experience; food consumption; glucose tolerance; glycemic control; gut dysbiosis; gut inflammation; gut microbiota; innovation; insight; insoluble fiber; insulin sensitivity; intravenous glucose tolerance test; microbial; microbiome; microbiota; middle age; novel; novel strategies; nutrition; polyunsaturated fat; saturated fat; soluble fiber; sugar; translational potential; treatment duration; treatment guidelines

Project Summary Advancing age is associated with gut dysbiosis, low-grade chronic inflammation, progressive insulin resistance, and increased risk of type 2 diabetes (T2D). Prediabetes is present in 45-50% of middle-aged/older adults, and declines in glucose tolerance are evident in the third or fourth decade of life. Thus, there is an urgent need to identify new approaches for the prevention of type 2 diabetes among middle-aged adults. Observational research has linked intake of ultra-processed foods (UPF), which comprise ~60% of total energy intake in US adults, with increased risk of T2D. Ex vivo and animal research suggests that components of UPF alter gut microbiota composition and initiate a cascade of events leading to intestinal inflammation and impaired glycemic control. Whether mid-life adults (aged 45-65 yrs) are susceptible to the adverse impact of UPF consumption on glucose homeostasis is unknown. The overall objective of this R21 proposal is to establish proof-of-concept for an impairment in glucose homeostasis following increases in UPF consumption in mid-life adults, in order to conduct a larger, more comprehensive and mechanistic trial in the future. In addition, we will investigate changes in gut microbial composition and function, intestinal inflammation and permeability, serum endotoxin concentrations, and inflammatory cytokines as potential mechanisms by which UPF consumption influences glucose homeostasis. To this end, following a two- week eucaloric lead-in diet, 42 healthy mid-life adults (45-65 yrs) will be randomly assigned to either a 6-week diet emphasizing UPF or minimally processed foods (no UPF). Participants will be fed a eucaloric diet (50% carbohydrate, 35% fat,15% protein) matched for dietary soluble and insoluble fiber, added sugar, mono- and polyunsaturated fat, saturated fat, antioxidant nutrients, sodium, pre- and probiotics, and overall diet quality, for the duration of the study to avoid potential confounds of weight change and other dietary factors which may influence study outcomes. Measurements of insulin sensitivity and beta cell function via IVGTT, 24-hr and postprandial glycemic control using continuous glucose monitoring (CGM), gut microbiota composition/function, fecal short chain fatty acids (SCFA), intestinal inflammation, intestinal permeability, serum endotoxin, and inflammatory cytokines will be made before and following the 6-week high UPF or no UPF diet period. This innovative study may contribute importantly to an emerging integrative physiological understanding of the adverse effects of UPF consumption in an understudied population, mid-life adults. Our proposal is responsive to PA-18-850 Prevention Research in Mid- life Adults, specifically the focus on “how age-related perturbations in the microbiome” may predispose mid-life adults to chronic disease. This research may also have clinical and public health impact by informing US dietary and T2D prevention and treatment guidelines which do not currently address total UPF consumption or older adults due to a lack of rigorously designed controlled trials.

项目摘要 年龄增长与肠道生物失调、低度慢性炎症、进行性胰岛素抵抗、 并增加患2型糖尿病(T2D)的风险。糖尿病前期存在于45%-50%的中老年人中，并且 糖耐量的下降在生命的第三个或第四个十年是明显的。因此，迫切需要确定 预防中年2型糖尿病的新方法。观察性研究发现 超加工食品(UPF)的摄入量，占美国成年人总能量摄入量的60%，并呈上升趋势 T2D的风险。体外和动物研究表明，UPF的成分改变了肠道微生物区系组成和 引发一系列导致肠道炎症和血糖控制受损的事件。无论是中年成年人 (45-65岁)易受UPF摄入对血糖稳态的不利影响，目前尚不清楚。 R21提案的总体目标是建立葡萄糖稳态受损的概念验证 随着中年成年人UPF消费量的增加，为了进行更大、更全面和 未来的机械化审判。此外，我们还将研究肠道微生物组成和功能的变化， 肠道炎症和通透性、血清内毒素浓度和炎性细胞因子是潜在的 UPF消耗影响血糖动态平衡的机制。为此，在进行了为期两周的 将42名健康的中年成年人(45-65岁)随机分配到6周的饮食中 强调UPF或最低限度加工的食品(没有UPF)。参与者将被喂以无糖饮食(50% 碳水化合物、35%脂肪、15%蛋白质)与膳食中可溶和不溶纤维相匹配，添加糖、单糖和 多不饱和脂肪，饱和脂肪，抗氧化营养素，钠，前和益生菌，以及总体饮食质量，对于 研究持续时间，以避免体重变化和其他可能影响饮食因素的潜在混淆 研究结果。通过IVGTT、24小时和餐后测量胰岛素敏感性和胰岛β细胞功能 应用连续血糖监测(CGM)、肠道微生物区系组成/功能、粪便短链控制血糖 脂肪酸(SCFA)、肠炎症、肠通透性、血清内毒素和炎性细胞因子 将在6周最高UPF或无UPF节食期前后进行。这项创新性的研究可能有助于 重要的是要对UPF消费的不利影响有一个新的综合生理学理解 研究不足的人群，中年成年人。我们的建议是回应PA-18-850中期的预防研究- 《成人生活》，特别是关注与年龄相关的微生物群的扰动如何可能使中年成年人倾向于 到慢性病。这项研究还可能通过告知美国饮食和T2D对临床和公共健康产生影响 预防和治疗指南目前没有涉及UPF的总消费量或由于以下原因而导致的老年人 缺乏严格设计的对照试验。