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: 10600848
• 负责人: Kristina Brooke Martinez-Guryn
• 金额: $ 15.86万
• 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/10600848
• 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; Epithelium; Esterification; Eukaryota; Fat-Restricted Diet; Fatty Acids; Fatty acid glycerol esters; Fluorescent in Situ Hybridization; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; 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; 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.

项目摘要 肥胖和糖尿病的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）-高糖饮食改变了肠道的微生物组成。 有趣的是，我们之前已经表明，HF饮食对小肠微生物群有很强的影响， 在营养消化和吸收的主要部位空肠中。此外，空肠HF微生物增加了脂质 与从空肠收集的低脂肪（LF）饮食微生物相比，在成年无菌小鼠中的吸收。但是，在这方面， 在这项研究中，我们集中在细菌类群，而不是真菌类群。文献中存在一个关键的空白 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 目的是阐明候选真菌如假丝酵母调节脂质吸收、脂肪 运输和肥胖。本申请的目的是确定念珠菌对酵母或 菌丝形态，对脂质消化吸收能力和肥胖发展的影响。此外，我们将研究 念珠菌沿着肠道的位置。我们的初步数据表明，C。酵母菌中的白色念珠菌 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- 杀死C。白色念珠菌还增加了喂食HF饮食的小鼠的体重增加，并诱导脂肪酸移位酶（Cd 36） 在空肠中表达。新出现的证据表明，饮食与肠道微生物的相互作用有可能 为了促进疾病，我们发展了我们的中心假设，即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： 对C.白色念珠菌和对宿主脂质摄取和肥胖的影响，目的2） 确定C.白色念珠菌介导的脂质吸收。我们只有 达到了解细菌如何调节营养消化和吸收的悬崖，甚至更少是 关于肠道真菌的作用。该研究具有创新性和重要意义， 将更好地定义小肠菌群，念珠菌的区域定位，并更好地定义 调节吸收的宿主-微生物相互作用的机制有助于肥胖的发展。