Red and Processed Meat Effects on the Metabolome and Microbiome

项目总结 最近出现了关于频繁摄入红肉和加工肉是否会成为 健康饮食，或者红肉和加工肉是否应该避免或只适量食用。 消费者和医疗保健专业人员被这些相反的观点搞糊涂了，需要研究来 明确指导饮食建议。观察队列发现，那些自我报告的人 经常摄入红肉和加工肉会增加罹患多种与饮食有关的慢性疾病的风险，例如 与那些摄入这些食物的人相比，心血管疾病、II型糖尿病和癌症的摄入量更低。 这些发现是有价值的，但自我报告的没有生物标记的饮食并不能推动科学进步 朝着了解生物机制的方向发展。一些队列研究报告了红色和红色之间的联系 加工肉类消费和与健康相关的生物标记物，如脂质或食品制剂-产生 生物标志物，如多环芳烃(PAHs)和杂环胺(HAS)。然而，许多人 这些研究检查了红肉和加工肉与血液或尿液生物标记物之间的关系。 分段分析，留下了残留混淆的可能性，无法得出因果推理。 此外，在这些研究中，通常只测量了一种途径或一种化合物，限制了对多个 受红肉和加工肉消费影响的路径。而且还没有研究对红色进行测试和处理 使用新陈代谢组和微生物组的系统范围生物标志物上的肉类。为了克服这些证据空白 我们将进行严格的随机交叉喂养试验，这是一种最适合于 研究将食物摄入量与代谢反应联系起来的机制，这是由于有能力仔细控制食物 入口处。这项试验性的控制喂养试验将招募20名健康的成年雌性和雄性。参与者将 按随机顺序消费两种饮食：1)饮食A基于2015年健康饮食指数(HEI-2015)和 不包括红肉或加工肉类；2)饮食B基于2015年健康饮食指数，包括红肉和 加工肉类(HEI-2015-M)作为主要蛋白质来源。这两种节食期分别为21天和21天 冲洗期发生在两次饮食之间。所有食物都是在新陈代谢的厨房里准备的，要么由 参与者或通过快递送货上门。两种类型的机械性生物标记物是这种情况的结果 这两项研究都反映了系统范围的读数：(1)代谢组学；(2)肠道微生物区系。血液，24小时尿液 在实验前后采集大便和粪便，以测试这些特定的目的：(1)确定程度 与HEI-2015-M相比，食用HEI-2015标准饮食时代谢组变化的性质 饮食；以及(2)确定和表征当食用标准时肠道微生物群落的调节 Hei-2015饮食与Hei-2015-M饮食的比较。这项试点试验预计将提供发现、机械性 关于红肉和加工肉摄入量对人体新陈代谢影响的数据，将用于设计和 为更大规模的随机对照试验提供动力。

PROJECT SUMMARY Recent controversy has arisen concerning whether frequent intake of red and processed meat can be part of a healthy diet, or whether red and processed meat should be avoided or consumed only in moderation. Consumers and health care professionals are confused by these opposing views and research is needed to definitively guide dietary recommendations. Observational cohorts have found that those who self-report frequent red and processed meat intake have higher risk of several diet-related chronic diseases such as cardiovascular disease, type II diabetes and cancer compared to those with low or no intake of these foods. These findings are valuable, but self-reported diet without biological markers does not advance science towards understanding biological mechanisms. Some cohort studies have reported links between red and processed meat consumption and health related biomarkers such as lipids or food preparation-generated biomarkers such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HAs). However, many of these studies examined the associations of red and processed meat with blood or urine biomarkers in cross- sectional analyses, leaving the possibility for residual confounding and an inability to draw causal inference. Further, often only one pathway or one compound was measured in these studies, limiting insight into multiple pathways affected by red and processed meat consumption. And no studies have tested red and processed meat on systems-wide biomarkers using the metabolome and microbiome. To overcome these evidence gaps we will conduct a rigorous randomized cross-over feeding trial, which is a study design optimally suited for investigating mechanisms linking food intake with metabolic response due to the ability to carefully control food intake. This pilot, controlled feeding trial will enroll 20 heathy adult females and males. Participants will consume two diets, in random order: 1) Diet A is based on the Healthy Eating Index-2015 (HEI-2015) and includes no red or processed meat; 2) Diet B is based on the Healthy Eating Index-2015 and includes red and processed meat (HEI-2015-M) as primary protein sources. Both diet periods last 21 days and a 21-day washout period occurs between diets. All food is prepared in a metabolic kitchen and either picked up by participants or delivered by courier to their homes. Two types of mechanistic biomarkers are outcomes for this study, both reflecting systems-wide readouts: (1) metabolomics; and (2) gut microbiota. Blood, 24-hour urine and stool are collected before and after the experimental diets to test these specific aims: (1) Identify the extent and nature of shifts in the metabolome when consuming a standard HEI-2015 diet compared to a HEI-2015-M diet; and (2) Identify and characterize modulation of the gut microbial community when consuming a standard HEI-2015 diet compared to a HEI-2015-M diet. This pilot trial is expected to provide discovery, mechanistic data on the impact of red and processed meat intake on human metabolism that will be used to design and power a larger randomized controlled trial.