Gut microbial promotion of energy gain from processed diets

肠道微生物促进加工饮食中的能量获取

• 批准号: 8646325
• 负责人: Rachel Naomi Carmody
• 金额: $ 4.92万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8646325
• 关键词: Address; Affect; Biological Availability; Calories; Carbohydrates; Clinical; Colon; Complex; Consumption; Data; Deposition; Diet; Dietary Carbohydrates; Disease; Ecology; Exhibits; Expenditure; Fatty acid glycerol esters; Food; Food Processing; Foundations; Future; Gastrointestinal tract structure; Germ-Free; Gnotobiotic; Goals; Health; Human; Individual; Intervention; Knowledge; Lead; Life Style; Link; Literature; Macronutrients Nutrition; Malnutrition; Meat; Mechanics; Methods; Mus; Nutrient; Nutritional; Obesity; Physiology; Plants; Process; Property; Research; Role; Shapes; Small Intestines; Structure; Sweet Potato; System; Taxon; Testing; Therapeutic; Translations; Transplantation; Weight Gain; Work; Xenobiotics; antimicrobial; cooking; energy balance; feeding; follow-up; foodborne; gut microbiota; human subject; improved; insight; microbial; microbial community; microbial host; microbiome; microorganism; microorganism interaction; mouse model; novel; obesity treatment; programs; public health relevance; research study

DESCRIPTION (provided by applicant): The trillions of microorganisms inhabiting the human gastrointestinal tract (gut microbiota) contribute importantly to energy balance, but their net effect on energy gain and expenditure is shaped by diet. While the impacts of altering diet quantity or composition have been studied, the impacts of processing a given diet by common methods like cooking or grinding remain unknown. A large literature indicates that food processing enhances energy gain by increasing the proportion of dietary carbohydrates that are assimilated in the small intestine. This reduces the fraction of nutrients passing undigested into the colon, where the densest microbial communities reside, and could thus be expected to limit the microbial contribution to energy gain. However preliminary data reveal dramatic impacts of a processed carbohydrate-rich plant diet on gut microbial ecology that instead favor microbial taxa known to stimulate host adiposity. These results, combined with those of prior studies, suggest that energy gain reflects complex interactions between host, dietary and microbial factors. This goal of this research program is to characterize the contributions of the gut microbiota to energy gain on processed diets. Benefiting from insight achieved in the comparison of conventional and gnotobiotic (germ-free or colonized) mice, the studies proposed will address three specific aims: Aim 1: Test alternative hypotheses for the impact of food processing on gut microbial communities, focusing on the roles of processing in increasing bioavailability and deactivating foodborne xenobiotics; Aim 2: Interrogate the microbial promotion of energy gain on processed diets through gnotobiotic experiments involving colonization and gut microbiota transplantation; and Aim 3: Extend work to other food substrates that exhibit distinct properties when processed, enabling tests of other putative mechanisms for the microbial promotion of energy gain. These studies will address novel mechanisms of host-microbial interaction, increasing our understanding of the ecological determinants of human health. Such work holds clinical promise because robust knowledge of microbial impacts on host physiology could lead to new treatments for disease via manipulation of the gut microbiota or its downstream host targets. Notably, food processing is an especially attractive possibility for intervention, being a ubiquitous and readily modifiable feature of the human diet. These advantages make this research program a fertile foundation for subsequent work involving a wide range of substrates and processing methods, more detailed analysis of host-microbial interactions, and eventual translation to human subjects.

描述（由申请人提供）：栖息在人类胃肠道（肠道微生物群）中的数万亿微生物对能量平衡有重要贡献，但它们对能量获得和消耗的净效应受饮食影响。虽然已经研究了改变饮食数量或组成的影响，但通过烹饪或研磨等常见方法处理给定饮食的影响仍然未知。大量文献表明，食品加工通过增加小肠吸收的膳食碳水化合物的比例来提高能量获得。这减少了未经消化进入结肠的营养成分的比例，其中存在着微生物群落，因此可以预期限制微生物对能量获得的贡献。然而，初步数据显示，富含碳水化合物的加工植物饮食对肠道微生物生态的巨大影响，反而有利于已知刺激宿主肥胖的微生物类群。这些结果与先前的研究相结合，表明能量增益反映了宿主，饮食和微生物因素之间复杂的相互作用。这项研究计划的目标是表征肠道微生物群对加工饮食能量增益的贡献。受益于在比较常规和非生物的（无菌或定殖）小鼠，拟议的研究将解决三个具体目标：目标1：测试食品加工对肠道微生物群落影响的替代假设，重点是加工在提高生物利用度和灭活食源性外源性物质方面的作用;目标2：通过涉及定植和肠道微生物群移植的gnotobiotic实验，探讨微生物对加工饮食能量获得的促进作用;目标3：将工作扩展到其他在加工时表现出不同特性的食品基质，从而能够测试微生物促进能量获得的其他推定机制。这些研究将解决宿主-微生物相互作用的新机制，增加我们对人类健康的生态决定因素的理解。这些工作具有临床前景，因为微生物对宿主生理学影响的强大知识可以通过操纵肠道微生物群或其下游宿主靶点来治疗疾病。值得注意的是，食品加工是一个特别有吸引力的干预可能性，是人类饮食的一个普遍存在的和容易改变的特征。这些优势使该研究计划为后续工作奠定了坚实的基础，这些工作涉及广泛的底物和加工方法、对宿主-微生物相互作用的更详细分析以及最终转化为人类受试者。