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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结