Role of Human Intestinal Microbiota on Success of Surgical Weight Loss Procedures

描述(申请人提供)：肥胖症在美国是一种日益严重的流行病。自1980年以来，成年人的肥胖率增加了75%以上，目前，超过一半的美国人口超重，近三分之一的成年人患有临床肥胖症。肥胖是身体调节能量摄入、消耗和储存方式改变的结果。最近，有研究表明，肠道微生物区系对能量提取有影响，从而导致肥胖。人类和小鼠的类杆菌比瘦小的人类和小鼠的类杆菌更少，而细菌的数量更多。此外，发酵菌和史密斯甲烷短杆菌(一种来自古生界的产甲烷菌)似乎通过共生作用影响能量的吸收。使用高通量分子方法，我们证实了肥胖和正常体重个体的微生物区系不同，并表明成功的减肥手术后患者的微生物区系是独特的。减肥手术是目前唯一可用的治疗病态肥胖的方法，它可以持续实现并保持实质性的体重减轻，降低肥胖相关并发症的发生率和严重性，并提高总体生活质量和生存能力。根据我们过去的工作，我们假设RYGB后肠道微生物区系发生的戏剧性变化可能在RYGB的成功和/或最终失败中发挥重要作用。这项拟议研究的主要目标是评估人体肠道微生物生态在减肥手术两种常见方法：Roux-en-Y胃分流术(RYGB)和腹腔镜可调胃带(LAGB)后对减肥成功或失败的作用。我们将：1)使用高通量测序来识别与特定的一组消费氢的微生物相互作用的发酵剂；2)使用定量聚合酶链式反应跟踪和量化腔内和粘膜消费氢微生物的存在；3)跟踪代谢产物并确定与能量提取相关的微生物的合成体和代谢功能；以及(4)通过数学建模使用生态学方法整合和解释结果。确定关键的同体营养伙伴关系应该揭示肥胖风险和减肥手术后成功减肥的有用标志。它们还应该导致基于微生物的治疗策略，以提高减肥手术和其他减肥方法的成功机会。 公共卫生相关性：该项目将调查生活在人体肠道中的微生物，以及它们如何影响两种减肥手术后减肥的成败。最终目标是找到有助于减肥手术后减肥的微生物。

DESCRIPTION (provided by applicant): Obesity is a growing epidemic in the United States. The prevalence of obesity in adults has increased by over 75% since 1980, and, presently, more than half of the United States population is overweight, with nearly 1 in 3 adults being clinically obese. Obesity arises as a consequence of alterations in how the body regulates energy intake, expenditure, and storage. Recently, it has been suggested that the gut microbiota has an effect in energy extraction, hence obesity. Humans and mice harbor fewer Bacteroidetes and more Firmicutes than those of their lean counterparts. Also, fermenters and Methanobrevibacter smithii (a methanogen from the Archaea domain) appear to act syntrophically to affect energy uptake. Using high- throughput molecular methods, we confirmed that the microbiota of obese and normal-weight individuals differ and showed that the microbiota in patients following successful bariatric surgery are unique. Bariatric surgery is currently the only available treatment for morbid obesity that consistently achieves and maintains substantial weight loss, decreases the incidence and severity of obesity-related co-morbidities, and improves overall quality of life and survival. Based on our past work, we hypothesize that the dramatic change in the intestinal microbiota that occurs following RYGB may play a significant role in the success and/or eventual failure of RYGB. The primary goal of the proposed research is to assess the role of the human- intestinal microbial ecology on success or failure to lose weight following two common methods of bariatric surgery: the Roux-en-Y gastric bypass (RYGB) and the laparoscopic adjustable gastric band (LAGB). We will: 1) Use high-throughput sequencing to identify fermenters that interact with a particular group of H2-consuming microorganisms; 2) Track and quantify the presence of luminal and mucosal H2-consuming microorganisms using quantitative PCR; 3) Track metabolic products and determine syntrophies and metabolic functions of the microorganisms associated with energy extraction; and (4) Integrate and interpret the results using an ecological approach through mathematical modeling. Identifying the key syntrophic partnerships should reveal useful markers of obesity risk and successful weight loss following bariatric surgery. They also should lead to microorganism-based therapeutic strategies to improve the chance of success of bariatric surgery and other weight- loss approaches. PUBLIC HEALTH RELEVANCE: This project will investigate microorganisms that live in the human intestines and how they affect success or failure of weight loss after two methods of bariatric surgery. The ultimate goal is to find microorganisms that help weight loss following bariatric surgery.