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

哺乳动物的肠道内大量存在着大量的常驻细菌。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健康关系至关重要。为了确保互惠互利的关系，肠道细菌通过排列在肠道内表面的单层细胞（称为上皮细胞）与宿主的免疫系统分开。此外，肠道内的免疫系统在某种程度上受到抑制，因此它不会攻击常驻细菌。目前尚不清楚哪些因素会抑制肠道免疫系统并维持与肠道微生物的健康相互作用，但我们和其他人最近发现维生素 D 可能参与其中。维生素 D 是一种重要的脂溶性维生素，可以通过暴露在阳光下或从饮食中获得。当小鼠的饮食中缺乏维生素 D 或遗传上缺乏维生素 D 受体时，它们的肠道会比喂食足量维生素 D 的小鼠表现出更严重的炎症。此外，缺乏维生素 D 与肠上皮渗漏有关，而肠上皮对免疫信号也更敏感。为了确定维生素 D 如何影响肠道与其所含微生物群之间的界面，我们将了解维生素 D 水平（及其对宿主的影响）是否会改变肠道微生物的构成。我们还将通过去除维生素 D 受体小鼠的免疫系统的特定部分，或让不同类型的免疫缺陷小鼠接受维生素 D 缺乏的饮食，来探索免疫系统的哪些部分正在驱动这些变化。最后，我们将定义肠道中需要维生素 D 信号传导来控制免疫和肠上皮反应的细胞类型，作为定义维生素 D 如何发挥其作用的另一种方法。总而言之，这些研究将有助于阐明饮食中的因素（例如维生素 D）如何帮助控制我们的肠道功能，并促进与微生物群的有益相互作用。

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.