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

肠道菌群在调节宿主脂质吸收和肥胖中的作用

• 批准号: 10453363
• 负责人: Kristina Brooke Martinez-Guryn
• 金额: $ 16.53万
• 依托单位: MIDWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10453363
• 关键词: 16S ribosomal RNA sequencing; Adult; Antibiotics; BODIPY; Bacteria; Binding; Biological Assay; Body Composition; Body Weight; C Type Lectin Receptors; CD36 gene; Candida; Candida albicans; Carbohydrates; Communities; Consumption; Data; Diabetes Mellitus; Diet; Digestion; Disease; Epithelial; Esterification; Eukaryota; Fat-Restricted Diet; Fatty Acids; Fatty acid glycerol esters; Fluorescent in Situ Hybridization; Gene Expression; Genes; Genetic; Germ-Free; Gnotobiotic; Goals; Health Care Costs; High Fat Diet; Human; Impairment; In Vitro; Insulin Resistance; Intestines; Knock-out; Knockout Mice; Knowledge; Length; Lipids; Literature; Macronutrients Nutrition; Mediating; Metabolic; Metabolic Diseases; Metabolic Marker; Metabolic dysfunction; Metabolism; Microbe; Molecular; Morphology; Mus; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obese Mice; Obesity; Organoids; Physiological Processes; Plasma; Play; Quality of life; Radiolabeled; Regulation; Research; Role; Saline; Shapes; Signal Transduction; Site; Small Intestines; Stains; Supplementation; Testing; Up-Regulation; Weight Gain; Work; Yeasts; absorption; bacterial community; base; diet-induced obesity; feeding; fungal microbiota; fungus; gastrointestinal; gut microbes; gut microbiome; gut microbiota; host-microbe interactions; innovation; jejunum; member; microbial; microbiome; microbiota; mycobiome; neglect; novel; novel strategies; obesity development; oral glucose tolerance; receptor; response; saturated fat; small molecule; sugar; targeted treatment; therapeutic development; transcriptome sequencing; translocase; uptake; western diet

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.

项目概要 肥胖和糖尿病的一个主要原因是食用富含饱和脂肪和简单的西式饮食。 糖。最近的研究表明，高脂肪（HF）高糖饮食会改变肠道微生物组成。 有趣的是，我们之前表明，高频饮食对小肠微生物群有强烈影响，特别是 空肠是营养物质消化和吸收的主要场所。此外，空肠高频微生物会增加脂质 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，我们关注的是细菌类群而不是真菌类群。文献中存在关键空白 关于真菌在调节肠道吸收能力以应对高频饮食方面的作用。我们的长期 目标是阐明念珠菌等候选真菌调节脂质吸收、脂肪的机制 运输和肥胖。本应用的目的是确定念珠菌对酵母或 菌丝形式，对脂质消化和吸收能力以及肥胖发展的影响。此外，我们将检查 念珠菌沿着肠道的长度定位。我们的初步数据表明酵母中的白色念珠菌 菌丝形式会引发参与脂肪吸收的基因上调。每周补充热量—— 杀死白色念珠菌还增加了饲喂 HF 饮食并诱导脂肪酸转位酶 (Cd36) 的小鼠的体重增加 在空肠中表达。新的证据表明饮食与肠道微生物的相互作用具有潜在的潜力 为了促进疾病，我们提出了我们的中心假设：肠道菌群有助于脂质吸收 和小肠的消化能力。提出了两个具体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质摄取和肥胖的影响，目标 2) 确定白色念珠菌介导的脂质吸收所涉及的分子机制。我们只有 已经达到了了解细菌如何调节营养物质消化和吸收的边缘，甚至更少 已知肠道真菌的作用。拟议的研究具有创新性和意义，因为它 将更好地定义小肠菌群、念珠菌的区域定位并更好地定义 调节吸收导致肥胖发展的宿主-微生物相互作用机制。