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

项目摘要 年龄增长与肠道生态失调、低度慢性炎症、进行性胰岛素抵抗、 2型糖尿病（T2 D）的风险增加。糖尿病前期存在于45-50%的中年/老年人中， 葡萄糖耐量的下降在生命的第三或第四个十年中是明显的。因此，迫切需要查明 预防中年人2型糖尿病的新方法。观察性研究表明， 超加工食品（UPF）的摄入量占美国成年人总能量摄入量的60%， T2 D风险离体和动物研究表明，UPF的组分改变肠道微生物群组成， 引发一系列事件，导致肠道炎症和血糖控制受损。无论中年人 (aged 45-65岁）易受UPF消耗对葡萄糖稳态的不利影响。 这项R21提案的总体目标是为葡萄糖稳态受损建立概念验证 随着中年人UPF消费量的增加，为了进行更大，更全面， 未来的机械试验此外，我们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作为潜在的 UPF消耗影响葡萄糖稳态的机制。为此，在为期两周的 42名健康中年人（45-65岁）将被随机分配到6周饮食组和6周饮食组， 强调UPF或最低限度加工食品（无UPF）。参与者将被喂食一个eucaloric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 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 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）进行血糖控制，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、血清内毒素和炎性细胞因子 将在6周高UPF或无UPF饮食期之前和之后进行。这项创新研究可能有助于 重要的是，对UPF消费的不良影响的新兴综合生理学理解， 一群未被充分研究的中年人我们的建议是响应PA-18-850中期预防研究， 生活成年人，特别是关注“微生物组中与年龄相关的扰动”可能使中年人更易患病 到慢性病。这项研究也可能通过告知美国饮食和T2 D而产生临床和公共卫生影响。 预防和治疗指南，目前没有解决总UPF消费或老年人，由于 缺乏严格设计的对照试验。

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.