Understanding the impact of food components and microbial metabolites on interactions of gut microbes with the immune system

目前关于肠道微生物与免疫系统相互作用的重要作用的证据引起了人们对益生菌、益生元和膳食纤维的强烈兴趣。然而，应用益生菌的最新知识和通过饮食策略来控制肠道微生物的尝试结果好坏参半。基于饮食-微生物策略的结果不仅取决于微生物、食物成分和由此产生的微生物代谢物，而且还受宿主因素的影响。例如，女性和男性在益生元对免疫系统的影响方面的差异表明，基于性别的因素可以产生饮食和肠道微生物治疗结果的差异。然而，在益生元和益生菌的研究中很少涉及这方面。关于使用益生菌的其他问题包括食用益生菌的食物对其活性的影响。肠上皮细胞（IEC）和抗原提呈细胞（APC）在肠道界面的免疫活动中是不可或缺的，它们在那里遇到肠道微生物、食物成分和微生物代谢物。微生物代谢物和可溶性介质越来越被认为是益生菌、饮食和肠道微生物对免疫系统影响的关键参与者。关于益生菌、食物成分、微生物代谢物和宿主影响的相互作用网络的知识空白必须填补，以便设计有效的使用策略。*** IEC和APC影响先天免疫和适应性免疫，因此是益生菌、其他肠道微生物和膳食成分信号的重要靶点。由于乳酸菌（LAB）是一种免疫调节肠道微生物，通常作为益生菌存在于食物中，因此它们是模拟肠道微生物与IEC和APC相互作用以及用于益生菌输送的食物的影响的有用工具。确定LAB通过与IEC和APC的相互作用影响免疫系统的机制是本研究的目标之一；另一个是了解通常用于传递益生菌的食物如何影响这些相互作用。其他关键目标是确定膳食纤维和益生元对免疫系统和微生物代谢物产生影响的性别差异，并利用这些发现来描述微生物代谢物对IEC和APC活性的影响。长期目标是促进有效的肠道微生物和基于食物的靶向免疫结果策略。了解乳酸菌、微生物代谢物和饮食对免疫系统影响的机制和相互作用，将有助于优化它们的使用，也有助于确定潜在的限制。参与这项研究的学员将获得经验和知识，为开发有效利用食物和益生菌的新方法做出贡献，以优化免疫活性和宿主防御，这是加拿大人日常生活中饮食策略的重要因素。

Current evidence for essential roles of gut microbe interactions with the immune system has generated strong interest in probiotics, prebiotics and dietary fibres. However, attempts to apply recent knowledge about probiotics and to manipulate gut microbes through strategic use of diet have had mixed results. Outcomes of diet-microbe based strategies not only depend on microbes, food components and the resulting microbial metabolites, but are also influenced by host factors. For example, differences between females and males in impact of prebiotics on the immune system show that sex-based factors can generate variation in outcomes of diet and gut microbe-based treatments. However, this aspect is rarely addressed in studies of prebiotics and probiotics. Other questions about use of probiotics include the impact that the foods they are consumed in have their activity. Intestinal epithelial cells (IEC) and antigen presenting cells (APC) are integral in immune activity at the intestinal interface, where they encounter gut microbes, food components and microbial metabolites. Microbial metabolites and soluble mediators are increasingly seen as key participants in effects of probiotics, diet and gut microbes on the immune system. Gaps in knowledge about the network of interactions involving probiotics, food components, microbial metabolites and host impact must be filled in order to design effective strategies for their use.*** IEC and APC influence innate and adaptive immunity, so are important targets of signals from probiotics, other gut microbes and dietary components. Because lactic acid bacteria (LAB) are immunomodulatory gut microbes often consumed in foods and as probiotics, they are useful tools to model gut microbe interactions with IEC and APC, and the impact of foods used for probiotic delivery. Defining mechanisms used by LAB to influence the immune system through interactions with IEC and APC is one goal of this research; another is understanding how foods commonly used to deliver probiotics affect these interactions. Other key goals are to determine differences between sexes in effects of dietary fibres and prebiotics on the immune system and on microbial metabolite production, and to use these findings to delineate the impact of microbial metabolites on IEC and APC activity. Long term goals are to facilitate effective gut microbial and food-based strategies for targeted immune outcomes. Understanding the mechanisms and interactions that drive effects of LAB, microbial metabolites and diet on the immune system will lead to optimization of their use and also to the definition of potential limitations. Trainees involved in this research will gain experience and knowledge to contribute to developing new approaches for effective use of foods and probiotics in optimizing immune activity and host defence, elements important for dietary strategies in the daily lives of Canadians.