The Gut Microbiota in Metabolic Surgery: A Multi-Ethnic, Multi-Omic, Longitudinal Study

代谢手术中的肠道微生物群：一项多种族、多组学、纵向研究

基本信息

批准号：
10551244
负责人：
Danxia Yu
金额：
$ 73.88万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
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：
2021-02-05 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10551244
关键词：
Affect African American population Assessment tool Atherosclerosis Bile Acids Biological Assay Blood Pressure Blood specimen Body mass index Cardiometabolic Disease Clinical Data Development Diet Diet Modification Dyslipidemias Effectiveness Enrollment Evaluation Feces Fiber Foundations Future General Population Genes Goals Guidelines Health Human Hypertension Individual Indoles Intake Intervention Investigation Knowledge LDL Cholesterol Lipoproteins Life Style Literature Longitudinal Studies Longitudinal cohort Metabolic Metabolic Diseases Metagenomics Metformin Microbe Modeling Non-Insulin-Dependent Diabetes Mellitus Obesity Operative Surgical Procedures Outcome Pathway interactions Patients Pharmaceutical Preparations Pilot Projects Population Positioning Attribute Prevotella Probiotics Prospective cohort Protocols documentation Recommendation Research Research Personnel Risk Risk Reduction Role Sample Size Sampling Studies Surveys Testing Time Study Translating Ursodeoxycholic Acid Visit Volatile Fatty Acids Work Yogurt atherosclerosis risk bariatric surgery beta-Hydroxybutyrate blood lipid cardiometabolism cardiovascular disorder risk care providers caucasian American clinical practice clinical predictors clinically significant cohort design detection assay experience glycemic control gut microbiome gut microbiota host microbiota improved innovation insight metabolomics microbial microbiome microbiota microbiota metabolites multi-ethnic multiple omics novel outcome prediction prevent primary outcome prospective recruit secondary outcome stool sample surgery outcome

项目摘要

PROJECT SUMMARY Metabolic and bariatric surgery is an emerging option to treat obesity-related metabolic diseases, e.g., type 2 diabetes, and prevent atherosclerotic cardiovascular disease (ASCVD). Metabolic surgery can profoundly alter the gut microbiota; meanwhile, gut microbiota and their metabolites may affect cardiometabolic outcomes after the surgery. Investigation of these “host-microbiota interactions” will offer novel mechanistic understanding of metabolic surgery and evidence for developing potential microbiota-based models/therapies to achieve better cardiometabolic health. Yet, longitudinal patient studies that examined pre- to post-surgery gut microbiota and their metabolites in relation to cardiometabolic outcomes are scarce. Existing studies are limited by small sample sizes XVXDOO\ Q , non-prospective design, no evaluation of microbial functionality nor activity (e.g., via multi-omics), and little consideration of diet or medication use. Of note, no studies have evaluated gut microbiota in relation to estimated 10-year ASCVD risk, which reflects the overall cardiometabolic benefit of metabolic surgery and is widely used in clinical practice per ACC/AHA guideline. Furthermore, no studies have included African Americans (AAs), a population with high rates of cardiometabolic diseases. We aim to fill these research gaps by establishing a longitudinal, multi-ethnic cohort of metabolic surgery patients and applying multi-omics to identify microbial features (e.g., species, pathways, and metabolites) associated with estimated 10-year ASCVD risk and/or improvements in A1C, blood pressure, and blood lipids. In a pilot study, we enrolled 20 patients (including AAs), collected longitudinal stool/blood samples, conducted surveys, and found significant changes in microbiome and microbial metabolites after surgery, demonstrating the feasibility and our ability to carry out the proposed full-scale study. Specifically, we will enroll and follow 200 patients to collect biospecimen and conduct surveys at pre-surgery and 3-month and 1-year post-surgery visits. We will evaluate pre- to post-surgery changes in gut microbiome and fecal and circulating levels of metabolites, especially microbiota-derived metabolites, and the prospective associations of pre-surgery and 3-month microbiome and metabolites with ASCVD risk and metabolic outcomes at 1-year post-surgery. We will also explore potential effect modifications by diet and medication, focusing on fiber intake and metformin use. Our proposed research will provide substantial novel data to advance our understanding of the role of gut microbiota in cardiometabolic improvements after metabolic surgery, which may translate into novel microbial approaches to identify and treat patients for better cardiometabolic health. Our team has extensive expertise in cardiometabolic diseases, diet-microbiota-host interactions, metagenomics and metabolomics in longitudinal cohorts, as well as in metabolic surgery with experiences as patients, care providers, and/or researchers, and thus, is uniquely positioned to accomplish the proposed research.

项目概要代谢和减肥手术是治疗肥胖相关代谢疾病（例如 2 型）的新兴选择糖尿病，并预防动脉粥样硬化性心血管疾病（ASCVD）代谢手术可以深刻改变。肠道微生物群；同时，肠道微生物群及其代谢物可能会影响心脏代谢结果对这些“宿主-微生物群相互作用”的研究将为我们提供新的机制理解。代谢手术和开发基于微生物群的潜在模型/疗法以实现更好效果的证据然而，纵向患者研究检查了手术前后的肠道微生物群和它们的代谢物与心脏代谢结果相关的现有研究很少。样本大小 XVXDOO\ Q ，非前瞻性设计，未评估微生物功能或活性（例如，通过多组学），并且很少考虑饮食或药物的使用。值得注意的是，没有研究评估肠道。微生物群与估计的 10 年 ASCVD 风险相关，反映了总体心脏代谢益处代谢手术并根据 ACC/AHA 指南广泛应用于临床实践此外，还没有研究表明。其中包括非洲裔美国人（AA），这是一个心血管代谢疾病发病率很高的人群。我们的目标是通过建立一个纵向的、多种族的代谢手术队列来填补这些研究空白患者并应用多组学来识别微生物特征（例如物种、途径和代谢物）与估计的 10 年 ASCVD 风险和/或 A1C、血压和血脂的改善相关。在一项试点研究中，我们招募了 20 名患者（包括 AA），收集了纵向粪便/血液样本，进行了调查发现手术后微生物组和微生物代谢物发生显着变化，证明具体来说，我们将招募并跟踪 200 名研究人员。患者在术前以及术后 3 个月和 1 年就诊时收集生物样本并进行调查。我们将评估肠道微生物组以及粪便和循环代谢物水平的术前和术后变化，特别是微生物群衍生的代谢物，以及术前和 3 个月的前瞻性关联我们还将了解术后 1 年微生物组和代谢物与 ASCVD 风险和代谢结果的关系。探索饮食和药物的潜在影响，重点关注纤维摄入和二甲双胍的使用。我们提出的研究将提供大量新数据，以增进我们对肠道作用的理解微生物群在代谢手术后心脏代谢改善中的作用，这可能转化为新的微生物我们的团队在识别和治疗患者以改善心脏代谢健康方面拥有丰富的专业知识。心脏代谢疾病、饮食-微生物群-宿主相互作用、纵向宏基因组学和代谢组学队列，以及具有患者、护理提供者和/或研究人员经验的代谢手术，以及因此，具有独特的优势来完成拟议的研究。