The role of the gut mycobiota in regulating host lipid absorption and obesity

项目总结 肥胖和糖尿病的一个主要原因是吃了富含饱和脂肪和简单的西式饮食 加糖。最近的研究表明，高脂(HF)-高糖饮食会改变肠道的微生物组成。 有趣的是，我们先前表明HF饮食对小肠微生物区系有很强的影响。 在空肠中，营养物质消化和吸收的主要部位。此外，空肠HF微生物还能增加血脂 与从空肠收集的低脂(LF)饮食微生物相比，成年无菌小鼠的吸收情况。然而， 在这项研究中，我们专注于细菌类群，而不是真菌类群。文学作品中存在着一个批判性的空白 关于真菌在调节肠道对HF饮食的吸收能力方面的作用。我们的长期合作 目的是阐明候选真菌如念珠菌调节脂肪吸收、脂肪吸收的机制。 交通工具和肥胖。这项应用的目的是确定念珠菌在酵母或 菌丝形态，对脂肪的消化吸收能力和肥胖的发展。此外，我们还将审查 假丝酵母菌在肠道中的定位。我们的初步数据表明，酵母中的白色念珠菌 菌丝形态触发了与脂肪吸收有关的基因的上调。每周补充热量- 被杀死的白色念珠菌也增加了喂食HF食物的小鼠的体重增加，并诱导了脂肪酸转位酶(CD36) 在空肠中表达。因为新出现的证据表明，饮食-肠道微生物的相互作用具有潜在的 为了促进疾病，我们发展了我们的中心假设，即肠道真菌生物群有助于脂肪吸收。 和小肠的消化能力。提出了两个具体的目标来检验这一假设：目标1) 测试白色念珠菌的定位和形态，以及对宿主脂肪摄取和肥胖的影响，目标2) 确定白念珠菌介导的脂质吸收的分子机制。我们只有 达到了了解细菌如何调节营养消化和吸收的边缘，甚至更少 已知肠道真菌的作用。拟议的研究具有创新性和重要意义，因为它 将更好地定义小肠真菌区系，念珠菌的区域定位，并更好地定义 调节吸收的宿主-微生物相互作用机制有助于肥胖的发展。

PROJECT SUMMARY A leading cause of obesity and diabetes is consumption of a Western-style diet rich in saturated fat and simple sugars. Recent research shows that high fat (HF)-high sugar diets alter the microbial composition of the gut. Interestingly, we previously showed that HF diets have a strong impact on the small bowel microbiota specifically in the jejunum, the major site of nutrient digestion and absorption. Moreover, jejunal HF microbes increased lipid absorption in adult germ-free mice compared to low fat (LF) diet microbes collected from the jejunum. However, in this study, we focused on the bacterial taxa as opposed to fungal taxa. A critical gap exists in the literature regarding the role of fungi in regulating the absorptive capacity of the gut in response to HF diets. Our long-term goal is to elucidate the mechanisms by which candidate fungi such as Candida regulate lipid absorption, fat transport and adiposity. The objective of this application is to determine the impact of Candida, in yeast or hyphal form, on lipid digestive and absorptive capacity and obesity development. In addition, we will examine the localization of Candida along the length of the gut. Our preliminary data demonstrate that C. albicans in yeast and hyphal form triggers the upregulation of genes involved in fat absorption. Weekly supplementation of heat- killed C. albicans also increased body weight gain in mice fed a HF diet and induced fatty acid translocase (Cd36) expression in the jejunum. As emerging evidence suggests that diet-gut microbe interactions have the potential to promote disease, we developed our central hypothesis that the gut mycobiota contributes to lipid absorptive and digestive capacity in the small intestine. Two specific aims are proposed to test this hypothesis: Aim 1) Test the localization and morphology of C. albicans and impact on host lipid uptake and obesity, Aim 2) Determine the molecular mechanisms involved in C. albicans-mediated lipid absorption. We have only reached the precipice of understanding how bacteria regulate nutrient digestion and absorption and even less is known regarding the role of intestinal fungi. The proposed research is innovative and significant because it will better define the small intestinal mycobiota, regional localization of Candida and better define the mechanisms of host-microbe interactions that regulate absorption contributing to the development of obesity.