Vitamin D - A Regulator of Host-Microbe Interactions in the Mammalian GI Tract?

维生素 D - 哺乳动物胃肠道中宿主-微生物相互作用的调节剂？

• 批准号: 436233-2013
• 负责人: Vallance, Bruce
• 金额: $ 6.27万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=596896
• 关键词: Vitamin; Regulator; Host; Microbe; Interactions

The intestinal tract of mammals is heavily colonized by large numbers of resident bacteria. These bacteria help digest food and promote the proper functioning of the intestine, so it is critical that the relationship between the intestine and the bacteria it contains is a healthy one. To ensure a mutually beneficial relationship, the gut bacteria are separated from the host's immune system by a single layer of cells (called epithelial cells) that lines the inner surface of the intestine. Moreover, the immune system within the intestine is somehow suppressed, so it does not attack the resident bacteria. At present it is unclear what factors suppress the intestinal immune system, and maintain healthy interactions with the gut microbes, however we and others have recently found that vitamin D might be involved. Vitamin D is an important fat-soluble vitamin that can be obtained through exposure to sunlight, or in the diet. When mice are missing vitamin D in their diets, or genetically lacking the vitamin D receptor, their intestines show greater inflammation than those of mice that are fed sufficient levels of vitamin D. Moreover lack of vitamin D is associated with a leaky intestinal epithelium that is also more responsive to immune signals. To define how vitamin D affects the interface between the intestine and the populations of microbes it contains, we will see if vitamin D levels (and its effects on the host) alters the makeup of the intestinal microbes. We will also explore what parts of the immune system are driving these changes, by removing specific parts of the immune system from vitamin D receptor mice, or by exposing different types of immunodeficient mice to vitamin D deficient diets. Lastly, we will define the cell types in the intestine that require vitamin D signaling to control immunity and intestinal epithelial responses, as an additional way to define how vitamin D exerts its effects. Taken together, these studies will help clarify how factors in the diet, such as vitamin D help control the functions of our intestines, and promote beneficial interactions with our microbiota.

哺乳动物的肠道大量寄生着大量的细菌。这些细菌有助于消化食物并促进肠道的正常功能，因此肠道与其所含细菌之间的关系是健康的至关重要。为了确保互利关系，肠道细菌与宿主的免疫系统由一层排列在肠道内表面的单层细胞(称为上皮细胞)隔开。此外，肠道内的免疫系统受到某种程度的抑制，因此它不会攻击驻留的细菌。目前还不清楚是什么因素抑制了肠道免疫系统，并与肠道微生物保持健康的相互作用，但我们和其他人最近发现可能与维生素D有关。维生素D是一种重要的脂溶维生素，可以通过暴露在阳光下或从饮食中获得。当小鼠在饮食中缺乏维生素D，或者由于遗传原因缺乏维生素D受体时，它们的肠道表现出比那些摄入足够水平维生素D的小鼠更严重的炎症。此外，缺乏维生素D与漏水的肠道上皮有关，后者也对免疫信号更敏感。为了确定维生素D如何影响肠道与其所含微生物种群之间的界面，我们将观察维生素D水平(及其对宿主的影响)是否会改变肠道微生物的组成。我们还将探索免疫系统的哪些部分正在推动这些变化，通过从维生素D受体小鼠中移除免疫系统的特定部分，或通过将不同类型的免疫缺陷小鼠暴露在维生素D缺乏的饮食中。最后，我们将定义肠道中需要维生素D信号来控制免疫和肠道上皮反应的细胞类型，作为定义维生素D如何发挥作用的另一种方式。综上所述，这些研究将有助于澄清饮食中的因素，如维生素D如何帮助控制我们肠道的功能，并促进与我们的微生物区系的有益互动。