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: 10431451
• 负责人: BRENDA M DAVY
• 金额: $ 21.01万
• 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 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10431451
• 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; 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; Prevention Guidelines; Prevention Research; Prevention approach; Probiotics; Process; Processed Meats; Production; Proteins; Public Health; Randomized; Reducing diet; Reproducibility; Research; Risk; Risk Factors; Serum; Sodium; Unsaturated Fats; Vitamins; Volatile Fatty Acids; age related; aged; blood glucose regulation; cytokine; design; diabetes risk; dietary; experience; food consumption; glucose monitor; 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 促进年龄与肠道营养不良，低度慢性炎症，进行性胰岛素抵抗相关， 并增加了2型糖尿病（T2D）的风险。糖尿病前期有45-50％的中年/老年人和 葡萄糖耐受性下降是生命的第三或第四个十年中的证据。那迫切需要确定 中年成年人预防2型糖尿病的新方法。观察研究已关联 摄入超级加工食品（UPF），其中约占美国成年人总能量摄入量的60％ T2D的风险。离体和动物研究表明，UPF的成分改变了肠道菌群组成和 引发一系列级联，导致肠道感染和血糖控制受损。中年人是否成年 （45 - 65岁）易受UPF消费对葡萄糖稳态的不利影响的影响。 该R21提案的总体目标是为葡萄糖稳态损害建立概念验证 在中期成年人的UPF消费增加之后，为了进行更大，更全面的和 机械试验将来。此外，我们将研究肠道微生物组成和功能的变化， 肠炎和渗透率，血清内毒素浓度和炎症细胞因子作为潜在 UPF消耗会影响葡萄糖稳态的机制。为此，遵循两周的时间 Eucaloric Lead-in Diet，42个健康的中年成年人（45-65岁）将随机分配给6周的饮食 强调UPF或最少加工的食物（无UPF）。参与者将获得欧洲饮食（50％ 碳含碳含量为35％的脂肪，15％蛋白）与饮食固体和不溶性纤维相匹配，添加糖，单糖，单和 多不饱和脂肪，饱和脂肪，抗氧化剂营养素，钠，预生物和益生菌以及整体饮食质量，用于 研究的持续时间避免了体重变化和其他饮食因素的潜在混淆，这些因素可能会影响 研究结果。通过IVGTT，24小时和餐后测量胰岛素敏感性和β细胞功能 使用连续葡萄糖监测（CGM），肠道菌群组成/功能，粪便短链的血糖控制 脂肪酸（SCFA），肠道感染，肠道通透性，血清内毒素和炎性细胞因子 将在6周高的UPF或UPF饮食期之前和之后进行。这项创新的研究可能有助于 重要的是，对UPF消费的不利影响的新兴综合物理理解 了解人口，中年成年人。我们的提议对中期中的PA-18-850预防研究做出了反应 生活成年人，特别是关注“微生物组中与年龄相关的扰动”的关注 慢性病。这项研究也可能通过通知美国饮食和T2D来产生临床和公共卫生的影响 预防和治疗指南目前尚未解决由于 缺乏严格设计的对照试验。