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

• 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
• 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

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.

项目摘要 代谢和减肥手术是治疗与肥胖相关代谢疾病的新兴选择，例如2型 糖尿病，预防动脉粥样硬化心血管疾病（ASCVD）。代谢手术可以深刻改变 肠道菌群；同时，肠道菌群及其代谢产物可能会影响心脏代谢结果 手术。对这些“宿主菌相互作用”的调查将提供对新的机械理解 代谢手术和开发潜在的基于微生物群的模型/疗法以取得更好的证据 心脏代谢健康。然而，纵向患者研究检查了手术前肠道菌群和 它们与心脏代谢结果有关的代谢产物很少。现有研究受到小的限制 样本大小xvxdoo \ q，非头士设计，没有评估微生物功能或活动（例如， 通过多词），很少考虑饮食或药物使用。值得注意的是，没有研究评估肠道 与估计的10年ASCVD风险有关的微生物群，这反映了总体心脏代谢益处 代谢手术，并在ACC/AHA指南中广泛用于临床实践。此外，没有研究 包括非洲裔美国人（AAS），该人口患心脏代谢疾病率高。 我们旨在通过建立纵向多种代谢手术来填补这些研究空白 患者并应用多摩学来鉴定微生物特征（例如，物种，途径和代谢产物） 与估计的10年ASCVD风险和/或A1C，血压和血脂的改善有关。 在一项试点研究中，我们招募了20名患者（包括AAS），收集了纵向大便/血液样本 调查，发现手术后微生物组和微生物代谢产物的显着变化，证明 我们进行拟议的全面研究的可行性和能力。具体来说，我们将注册并关注200 在手术前，三个月和1年手术后就诊时收集生物传播并进行调查的患者。 我们将评估肠道微生物组和粪便和循环水平的代谢物的术前变化， 特别是微生物群的代谢产物，以及手术前和3个月的前瞻性关联 在手术后1年，具有ASCVD风险和代谢结果的微生物组和代谢产物。我们也会 通过饮食和药物探索潜在的效果修饰，专注于摄入纤维和二甲双胍的使用。 我们提出的研究将提供大量的新数据，以促进我们对肠道作用的理解 代谢手术后心脏代谢改善中的微生物群，这可能转化为新型微生物 识别和治疗患者以获得更好的心脏代谢健康的方法。我们的团队拥有广泛的专业知识 心脏代谢性疾病，饮食 - 微生物群 - 宿主相互作用，近代和代谢组学 同类以及具有患者，护理提供者和/或研究人员的代谢外科手术，以及 因此，在完成拟议的研究方面是独特的定位。