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

描述（由申请人提供）：肥胖在美国是一种日益严重的流行病。自1980年以来，成年人肥胖症的患病率增加了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临床肥胖。肥胖是由于身体调节能量摄入、消耗和储存的方式发生改变而引起的。最近，有人提出肠道微生物群对能量提取有影响，因此肥胖。人类和小鼠比他们的瘦同伴携带更少的拟杆菌门和更多的厚壁菌门。此外，发酵菌和史氏甲烷短杆菌（一种产甲烷菌）似乎以互养方式影响能量吸收。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群不同，并表明成功减肥手术后患者的微生物群是独特的。减肥手术是目前唯一可用的病态肥胖治疗方法，可持续实现并维持显著的体重减轻，降低肥胖相关合并症的发生率和严重程度，并改善整体生活质量和生存率。基于我们过去的工作，我们假设在RYGB之后发生的肠道微生物群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。拟议研究的主要目标是评估人类肠道微生物生态学在减肥手术的两种常见方法成功或失败后的作用：Roux-en-Y胃旁路术（RYGB）和腹腔镜可调节胃束带（LAGB）。我们将：1）使用高通量测序来鉴定与特定组的H2消耗微生物相互作用的发酵器; 2）使用定量PCR来追踪和定量腔和粘膜H2消耗微生物的存在; 3）追踪代谢产物并确定与能量提取相关的微生物的合成营养体和代谢功能;（4）运用生态学的方法，通过数学模型对结果进行整合和解释。确定关键的互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物。他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。

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.