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: 10093513
• 负责人: Danxia Yu
• 金额: $ 52.42万
• 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/10093513
• 关键词: Affect; African American; 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; Patient Care; Patients; Pharmaceutical Preparations; Pilot Projects; Population; Positioning Attribute; Prevotella; Prospective cohort; Protocols documentation; 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; base; beta-Hydroxybutyrate; blood lipid; cardiometabolism; cardiovascular disorder risk; care providers; caucasian American; clinical practice; clinical predictors; clinically significant; cohort; design; 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，预防动脉粥样硬化性心血管疾病（ASCVD）。代谢手术可以彻底改变 肠道微生物群;同时，肠道微生物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-微生物群相互作用”的研究将提供新的机制理解， 代谢手术和证据，用于开发潜在的基于微生物群的模型/疗法，以实现更好的 心脏代谢健康然而，纵向患者研究检查了手术前后的肠道微生物群， 它们与心脏代谢结果有关的代谢物很少。现有的研究局限于小 样本量XVXDOO\ Q，非前瞻性设计，未评价微生物功能性或活性（例如， 通过多组学），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 微生物群与估计的10年ASCVD风险相关，这反映了 根据ACC/AHA指南，代谢手术广泛用于临床实践。此外，没有任何研究 包括非裔美国人（AAs），这是一个心脏代谢疾病发病率高的人群。 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 患者和应用多组学来鉴定微生物特征（例如，种属、途径和代谢物） 与估计的10年ASCVD风险和/或A1 C、血压和血脂改善相关。 在一项初步研究中，我们招募了20名患者（包括AA），收集了纵向粪便/血液样本， 调查，并发现手术后微生物组和微生物代谢物的显着变化，证明 进行建议的全面研究的可行性和能力。具体来说，我们将招募并跟踪200名 患者在术前、术后3个月和1年访视时采集生物标本并进行调查。 我们将评估手术前后肠道微生物组以及代谢物的粪便和循环水平的变化， 尤其是微生物衍生的代谢产物，以及术前和术后3个月的前瞻性相关性 微生物组和代谢物与术后1年ASCVD风险和代谢结局的关系。我们还将 探索饮食和药物的潜在影响，重点是纤维摄入和二甲双胍的使用。 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。 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 识别和治疗患者以改善心脏代谢健康的方法。我们的团队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，宏基因组学和代谢组学 队列，以及作为患者、护理提供者和/或研究人员的代谢手术经验，以及 因此，是唯一的定位，以完成拟议的研究。