Gut microbial promotion of energy gain from processed diets

描述(申请人提供)：生活在人类胃肠道(肠道微生物区系)的数万亿微生物对能量平衡有重要贡献，但它们对能量获取和消耗的净影响是由饮食决定的。虽然改变饮食数量或组成的影响已经被研究，但通过烹饪或研磨等常见方法处理给定饮食的影响仍不清楚。大量文献表明，食品加工通过增加食物中碳水化合物在小肠中的同化比例来提高能量获得。这减少了未被消化的营养物质进入结肠的比例，而结肠是微生物群落最密集的地方，因此可能会限制微生物对能量获得的贡献。然而，初步数据显示，加工后的富含碳水化合物的植物饮食对肠道微生物生态产生了巨大影响，相反，有利于刺激宿主肥胖的微生物分类群。这些结果与以前的研究结果相结合，表明能量增加反映了宿主、饮食和微生物因素之间的复杂相互作用。这项研究计划的目标是表征肠道微生物区系对加工饲料能量获得的贡献。受益于对常规小鼠和格氏菌(无菌或定植)小鼠的比较，拟议的研究将针对三个具体目标：目的1：测试食品加工对肠道微生物群落的影响的替代假说，侧重于加工在提高生物利用度和使食源性异生生物失活方面的作用；目标2：通过涉及定植和肠道微生物区系移植的生态学实验，询问微生物促进加工饲料获得能量的作用；目标3：将工作扩展到其他在加工时表现出不同性质的食品基质，使能够测试微生物促进能量获得的其他可能机制。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。这项工作具有临床前景，因为关于微生物对宿主生理影响的可靠知识可能会通过操纵肠道微生物区系或其下游宿主靶标来导致疾病的新疗法。值得注意的是，食品加工是一种特别有吸引力的干预可能性，因为它是人类饮食中无处不在且随时可以改变的特征。这些优势使该研究计划为涉及广泛底物和加工方法的后续工作、更详细的宿主-微生物相互作用分析以及最终翻译到人类受试者奠定了肥沃的基础。

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.