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.

项目概要 年龄增长与肠道菌群失调、低度慢性炎症、进行性胰岛素抵抗、 45-50% 的中年/老年人患 2 型糖尿病 (T2D) 的风险增加，并且 糖耐量下降在三岁或四岁的时候很明显，因此，迫切需要确定这一点。 观察性研究发现了预防中年人 2 型糖尿病的新方法。 超加工食品 (UPF) 的摄入量约占美国成年人总能量摄入量的 60%，并且增加 离体和动物研究表明，UPF 的成分会改变肠道微生物群的组成并降低 T2D 的风险。 引发一系列事件，导致肠道炎症和血糖控制受损，无论是中年成年人。 （45-65 岁）是否容易受到 UPF 消耗对葡萄糖稳态的不利影响尚不清楚。 该 R21 提案的总体目标是针对葡萄糖稳态受损建立概念验证 随着中年成年人 UPF 消费量的增加，为了进行更大规模、更全面和 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、血清内毒素浓度和潜在的炎症细胞因子 UPF 影响葡萄糖稳态的机制 为此，经过两周的研究。 真热量引导饮食，42 名健康中年成年人（45-65 岁）将被随机分配接受 6 周饮食 强调 UPF 或最低限度加工食品（无 UPF） 参与者将接受无热量饮食（50%）。 碳水化合物，35% 脂肪，15% 蛋白质）与膳食可溶性和不溶性纤维、添加糖、单糖和单糖相匹配 多不饱和脂肪、饱和脂肪、抗氧化营养素、钠、益生菌和益生菌以及整体饮食质量， 研究的持续时间，以避免体重变化和其他可能影响的饮食因素的潜在混淆 通过 IVGTT、24 小时和餐后测量胰岛素敏感性和 β 细胞功能。 使用连续血糖监测 (CGM) 控制血糖、肠道微生物群组成/功能、粪便短链 脂肪酸 (SCFA)、肠道炎症、肠道通透性、血清内毒素和炎症细胞因子 这项创新研究将在 6 周高 UPF 或无 UPF 饮食期之前和之后进行。 对 UPF 摄入的不利影响的新兴综合生理学理解具有重要意义 我们的提案响应了 PA-18-850 中年预防研究。 成年人的生活，特别是关注“微生物组中与年龄相关的扰动”如何可能导致中年成年人患病 这项研究还可能通过告知美国饮食和 T2D 来产生临床和公共健康影响。 预防和治疗指南目前并未解决 UPF 总消耗量或老年人的问题，因为 缺乏严格设计的对照试验。