The role of gut microbes and microbial derived metabolites in the development of type 2 diabetes in humans

肠道微生物和微生物衍生代谢物在人类 2 型糖尿病发展中的作用

基本信息

批准号：
10657617
负责人：
Amit Majithia
金额：
$ 64.27万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-02 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10657617
关键词：
Address Adipocytes Amino Acids Bile Acids Biochemical Biological Biological Markers Branched-Chain Amino Acids Circulation Clinical Complex Computational Biology Data Development Diabetes Mellitus Disease Enrollment Environmental Risk Factor Enzymes Epidemiology Etiology Exposure to Fasting Gene Cluster Genetic Genome Glucuronides Health Hepatocyte Human Human Microbiome In Vitro Individual Inflammation Insulin Insulin Resistance Interleukin-6 Investigation Knowledge Laboratories Link Maps Mass Spectrum Analysis Mediation Metabolic Metagenomics Metformin Microbe Molecular Mus Non-Insulin-Dependent Diabetes Mellitus Pathology Pathway interactions Pharmaceutical Preparations Phenotype Plasma Prospective Studies Research Personnel Role Sampling Shotguns United States National Institutes of Health Validation Variant Volatile Fatty Acids Work cohort design diabetic dysbiosis fasting glucose fecal microbiome fecal transplantation follow-up gut microbes gut microbiome gut microbiota in vivo machine learning method metabolomics metagenomic sequencing microbial microbial genome microbiome microbiome alteration microbiome research multidisciplinary novel prospective secondary metabolite skills small molecule whole genome

项目摘要

PROJECT SUMMARY Mounting evidence links the gut microbiome – the modifiable “second genome” consisting of trillions of diverse microbes that inhabit the human gut – with type 2 diabetes mellitus (T2DM) in humans. Studies using fecal transplant in mice have raised the central hypothesis that changes of the gut microbiome and the biochemical by-products originated from these microbes may be key modulators of development of T2DM. To date, however, knowledge of the specific microbial species that drive the development of T2DM in humans remain very limited. Human studies of the gut microbiome in T2DM have largely been cross-sectional and confounded by reverse causality. Indeed, many of the gut microbiome changes observed in human T2DM have been found to be a consequence of the disease or treatments, including the medication metformin, rather than a cause of T2DM. In addition, the circulating metabolites derived from the gut microbes that contribute to the development of T2DM remain to be discovered. In this Early Stage Investigator NIH R01 application, we propose the largest prospective study of the role of gut microbiome in T2DM using a Finnish cohort of 6921 individuals with fecal and plasma samples collected in 2002 and over 15 years of subsequent clinical follow up. This proposed study brings together a diverse team with deep expertise in the human microbiome, mass-spectrometry based metabolomics, computational biology, statistical epidemiology, and diabetes pathobiology, to specifically address the key biological and clinical questions regarding the role of gut microbes and microbial derived metabolites in the development of incident T2DM in humans.

项目摘要安装证据链接肠道微生物组 - 可修改的“第二基因组”，由数万亿居住在人类肠道的潜水微生物 - 人类中有2型糖尿病（T2DM）。在小鼠中使用粪便移植的研究提出了肠道变化的中心假设微生物组和生化副产品起源于这些微生物可能是关键调节剂 T2DM的发展。但是，迄今为止，知道驱动驱动的特定微生物物种人类T2DM的发展仍然非常有限。 T2DM中肠道微生物组的人体研究在很大程度上是横断面的，并因反向休闲而混淆。确实，许多肠子发现在人T2DM中观察到的微生物组变化是该疾病的结果或包括药物二甲双胍在内的治疗，而不是T2DM的原因。另外，源自肠道微生物的循环代谢产物，导致T2DM的发展仍然有待发现。在这个早期的调查员NIH R01应用中，我们提出了最大的前瞻性研究使用6921个个体的芬兰队列肠道微生物组在T2DM中的作用在2002年收集的粪便和血浆样品以及随后的15年以上的临床随访。这项拟议的研究汇集了一个在人类微生物组中具有深厚专业知识的潜水团队，基于质谱的代谢组学，计算生物学，统计流行病学和糖尿病病理学，专门解决有关的关键生物学和临床问题肠道微生物和微生物衍生代谢产物在入射T2DM中的作用人类。