Mediating Role of Gut Microbiota in the Regulation of Colorectal Cancer Risk in the Context of Time-restricted Eating and Calorie Restriction

限时饮食和热量限制背景下肠道微生物群在结直肠癌风险调节中的中介作用

• 批准号: 10818119
• 负责人: Lisa Tussing-Humphreys
• 金额: $ 22.29万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10818119
• 关键词: Adherence; Anti-Inflammatory Agents; Butyrates; Caloric Restriction; Calories; Cancer Prevention Intervention; Colon; Colorectal Cancer; Communication; Diet; Eating; Environment; Exposure to; Faculty; Gene Expression Profile; Genetic; Goals; Hispanic; Hour; Inflammatory; Infrastructure; Intermittent fasting; Life Style; Malignant Neoplasms; Mediating; Mediation; Metabolic; Metabolism; Metagenomics; Methodology; Methods; Mucous body substance; Multiomic Data; Nutrient; Obesity; Pathway Analysis; Play; Prevention; Production; Regulation; Research; Research Personnel; Resolution; Risk Factors; Role; Sample Size; System; Time; Time-restricted feeding; Training; United States; Weight maintenance regimen; Woman; cancer prevention; career; colon carcinogenesis; colorectal cancer prevention; colorectal cancer risk; gastrointestinal; gut microbiota; host-microbe interactions; improved; innovation; insight; metabolomics; microbial; microorganism; parent grant; permissiveness; response; tenure track; Adherence; Anti-Inflammatory Agents; Butyrates; Caloric Restriction; Calories; Cancer Prevention Intervention; Colon; Colorectal Cancer; Communication; Diet; Eating; Environment; Exposure to; Faculty; Gene Expression Profile; Genetic; Goals; Hispanic; Hour; Inflammatory; Infrastructure; Intermittent fasting; Life Style; Malignant Neoplasms; Mediating; Mediation; Metabolic; Metabolism; Metagenomics; Methodology; Methods; Mucous body substance; Multiomic Data; Nutrient; Obesity; Pathway Analysis; Play; Prevention; Production; Regulation; Research; Research Personnel; Resolution; Risk Factors; Role; Sample Size; System; Time; Time-restricted feeding; Training; United States; Weight maintenance regimen; Woman; cancer prevention; career; colon carcinogenesis; colorectal cancer prevention; colorectal cancer risk; gastrointestinal; gut microbiota; host-microbe interactions; improved; innovation; insight; metabolomics; microbial; microorganism; parent grant; permissiveness; response; tenure track

PROJECT ABSTRACT The goal of this Diversity Supplement is to extend the significance and innovation of the Parent grant by examining the effect of time-restricted eating (TRE) and daily calorie restriction (CR) on the gut microbiota (GM) and host-microbial interactions relevant to the prevention of colorectal cancer (CRC), the third most incident cancer in the United States. The Diversity Supplement will also provide essential training in cancer prevention to a promising Hispanic woman and Early-Stage Career Investigator, Dr. Beatriz Peñalver Bernabé. Obesity is a major modifiable lifestyle risk factor for CRC. TRE is emerging as an alternative approach to managing weight that involves simply watching the clock and eating for 4-10 hours daily, thus restricting the body’s exposure to nutrients for extended periods of time. TRE demonstrates excellent adherence as it is simple and omits burdensome calorie counting, a hallmark of traditional daily CR. The GM can produce beneficial metabolites, such anti-inflammatory butyrate, or improve gut integrity by promoting mucus production, but a dysregulated GM can lead to increase colonic levels of pro-inflammatory and cancer-promoting metabolites. Existing studies on the effects of TRE on the GM are limited in scope and methodology due to small samples sizes, short duration, use of low-resolution methods that fail to examine changes in microbial metabolic function, and lack of a robust assessment of host-microbial interactions in response to TRE. Further, the differential effects of TRE versus CR on the GM and the relevance to colonic carcinogenesis remains unknown. We hypothesize that both TRE and CR will promote a GM environment less permissive of colonic carcinogenesis and that TRE will be superior due to differences in nutrient exposures, a downstream effect of the shortened eating window. Further, we surmise that systems-level approaches, such as network analysis, can identify the key communications between the host and microbial metabolic and colon genetic networks that play mechanistic roles in CRC risk and prevention. Levering the infrastructure of the Parent grant, the proposed Diversity Supplement will use high-resolution methods, such as metagenomics and metabolomics, to characterize GM composition and metabolic function and host systemic metabolism. Statistical and network approaches will be employed to integrate these multi- omics data and colonic transcriptional profiles to determine the effect of TRE and CR on GM and host-microbial interactions. We aim to examine the microbial-regulated metabolite signatures and host-microbial interactions in response to TRE and daily CR while promoting and enhancing diversity among cancer prevention researchers. The Diversity Supplement will provide needed insight into the modulation of the GM and host-microbial interactions in response to TRE and CR and its relevance to the prevention of colorectal carcinogenesis.

项目摘要 这种多样性补充的目的是扩展父母赠款的重要性和创新 检查时间限制饮食（TRE）和每日卡路里限制（CR）对肠道菌群（GM）的影响 和与预防结直肠癌（CRC）相关的宿主微生物相互作用，第三次事件 在美国的癌症。多样性补充剂还将提供预防癌症的基本培训 肥胖是一位有前途的西班牙裔女性，也是早期职业生涯的调查员BeatrizPeñalverBernabé博士。 CRC的主要可修改生活方式风险因素。 TRE正在成为管理体重的另一种方法 这涉及简单地观看时钟和每天吃4-10个小时，从而限制了身体的暴露 长时间的营养。 TRE表现出极好的依从性，因为它很简单，忽略了 繁重的卡路里计数，传统每日CR的标志。通用汽车可以产生有益的代谢物， 这种抗炎的丁酸酯，或通过促进粘液产生提高肠道完整性，但通用汽车失调 可能导致促炎和促进癌症的代谢产物的结肠水平。现有研究 TRE对GM的影响范围和方法限制，因为小样本尺寸，持续时间短， 使用低分辨率方法，无法检查微生物代谢功能的变化，并且缺乏强大的 响应TRE的宿主微生物相互作用的评估。此外，TRE与CR的差异效应 在GM上以及与结肠癌的相关性仍然未知。我们假设TRE和 CR将促进GM环境较少允许的结肠致癌，而TRE将是优越的 营养暴露的差异，缩短饮食窗口的下游效果。此外，我们冲浪 系统级方法（例如网络分析）可以识别主机之间的关键通信 以及在CRC风险和预防中扮演机械作用的微生物代谢和结肠遗传网络。 利用父母赠款的基础设施，拟议的多样性补充剂将使用高分辨率 诸如宏基因组学和代谢组学之类的方法来表征GM组成和代谢功能 和宿主系统性代谢。将雇用统计和网络方法来整合这些多重 OMICS数据和结肠转录曲线，以确定TRE和CR对GM和宿主微生物的影响 互动。我们旨在检查微生物调节的代谢产物特征和宿主 - 微生物相互作用 为了响应TRE和每日CR，同时促进和增强了预防癌症研究人员的多样性。 多样性补充剂将为转基因和宿主 - 微生物的调节提供所需的见解 响应TRE和CR的相互作用及其与预防结直肠癌的相关性。