Dietary, microbial, and host-derived mechanisms involved in modulating the integrity and function of the colonic microenvironment

我的研究平台的长期目标是进一步了解富含纤维的食物成分及其微生物衍生的代谢物与结肠微环境(微生物区系和粘膜)之间的相互作用，以及它们对健康的结肠粘膜屏障以及上皮细胞和免疫细胞动态平衡的完整性和功能的影响。本文提出的研究计划是基于我之前工作的逻辑进程，并将重点放在一种富含纤维的食物类型--亚麻籽(FS)上，以作为一种模型食物，使有益的微生物衍生代谢物，特别是短链脂肪酸(SCFA)和木脂素，以及来自FS蛋白质的潜在有害微生物代谢物，能够在体内有效地在结肠中传递，用于机制研究。我的短期目标是：1)在体内确定FS及其成分调节健康的结肠粘膜屏障以及上皮细胞和免疫细胞动态平衡的结构和功能的机制。2)在体内和体外确定肠道微生物区系的因果作用以及微生物代谢产物在多大程度上驱动FS对结肠微环境的影响。这项拟议的计划将首次全面评估FS及其生物活性成分对结肠微环境结构和功能的关键方面的影响，并提供FS诱导其影响的机制。提供富含纤维的植物食品的各种影响的基础知识，对于指导农业食品部门和食品政策机构关于功能性食品开发和与纤维相关的健康主张的决策将是重要的。

The long-term objective of my research platform is to further our understanding of the interplay between fiber-rich food components and their microbial-derived metabolites with the colonic microenvironment (microbiota and mucosa) and their effects on the integrity and function of the healthy colonic mucosal barrier and epithelial and immune cell homeostasis. The research program proposed herein is based on the logical progression of my previous work, and will focus on one fiber-rich food type, flaxseed (FS), to serve as a model food to enable effective in vivo colonic delivery of beneficial microbial-derived metabolites, specifically, short chain fatty acids (SCFAs) and lignans, as well as potentially adverse microbial metabolites from FS protein, for mechanistic investigations. My short-term objectives are: 1) to determine in vivo the mechanisms through which FS and its components, modulate the structure and function of the healthy colonic mucosal barrier and epithelial and immune cell homeostasis. 2) to determine in vivo and in vitro a causal role of the gut microbiota and the extent to which microbial metabolites drive FS-mediated effects on the colonic microenvironment. This proposed program will provide the first comprehensive assessment of the impact of FS, and its bioactive components, on critical aspects of the structure and function of the colonic microenvironment, and provide mechanisms through which FS induces its effects. Providing fundamental knowledge of the diverse effects of fiber-rich plant foods will be important in guiding decisions regarding functional food development and fiber-related health claims by the Agri-Food sector and food policy agencies.