The Microbiology of Bariatric Surgery
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 2
- 主要终点
- Fecal microbial analysis
研究概览
简要总结
Obesity and its associated diseases are increasing worldwide. However, the mechanisms behind the development of obesity is not fully understood. There is evidence that intestinal bacteria may play a role in the development and perpetuation of obesity through regulation of energy and fat storage.
Bariatric surgery is currently the most effective modality for treating severe obesity with evidence to support long-term sustained weight loss and improvement in obesity-related comorbidities. The two most commonly performed bariatric surgical procedures are the Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). RYGB leads to greater weight loss than SG and improved diabetes control in patients following surgery. Despite the success of RYGB and SG in inducing weight loss and improving comorbidities, the underlying mechanisms leading to clinical improvement following these operations is not completely understood. Multiple factors are thought to play a role including reduced caloric intake, decreased nutrient absorption, increased satiety, release of hormones and shifts in bile acid metabolism.
Recent evidence has suggested that the gut bacteria mediates a number of the beneficial effects of bariatric surgery. Small studies have demonstrated changes in the composition and diversity of the gut microbiota after RYGB and SG in humans. One study also confirmed long-term microbial changes for RYGB. However, comparative trials have been small (less than 15 participants per treatment group) and important differences between specific bacterial populations have not been well elucidated. Furthermore, no human study has examined the differences in bacterial composition following RYGB and SG in relation to their metabolic consequences.
The aim of this study is to investigate and compare the metabolic and microbial changes that occur with RYGB, SG, and dietary controls. Specifically, the investigators aim to use a systems biology approach utilizing powerful analytic techniques including metagenomics, metabolomics, and multiplex immune profiling to define the combined microbial, metabolic and immunologic changes that occur after bariatric surgery.
详细描述
HYPOTHESIS The investigators hypothesize that intestinal microbial dysbiosis and a decrease in diversity contributes to the development and perpetuation of obesity. The effect of dysbiosis is multifactorial and includes a decrease in intestinal barrier function and resultant local and systemic inflammation that incites the metabolic syndrome. The altered intestinal physiology following RYGB and SG will lead to identifiable changes in specific microbial populations and an increase in diversity. Specific beneficial microbial changes will subsequently result in weight loss, reduced inflammation, and a normalized metabolic profile.
METHODS Study population: Patients will be recruited from the Edmonton Adult Specialty Bariatric Clinic at the Royal Alexandra hospital.
Sample size: Each cohort of RYGB, SG and non-surgical dietary controls will have 30 patients (total n = 90). Previous studies have included 15 or less participants per arm.
Sample size calculation: Sample size calculation was designed to ensure the study would adequately capture microbial changes induced by surgery. In prior literature, an important short-chain fatty acid-producing bacterial species' (F. prausnitzii) relative abundance was lower in a post-RYGB group compared to non-operative controls (0.031 v. 0.053 σ 0.024). With an alpha of 0.05 and a Beta of 0.90, this would require 26 subjects per arm. Including a dropout rate of 10%, this increases to 30 subjects per arm.
Study design: For the intervention arm, subjects will be enrolled at the time they are scheduled for surgery. Fecal, urine, and blood samples will be collected in clinic 2-6 weeks prior to surgery. In the post-operative period, fecal collection will take place at scheduled three- and nine- month clinic visits. All pre-operative samples will be collected prior to subjects initiating a 2-4 week pre-operative liquid designed to reduce hepatomegaly and ease in the technical surgical aspects of the procedure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •30 severely obese controls: BMI > 35 kg/m2
- •30 severely obese patients scheduled for sleeve gastrectomy
- •30 severely obese patients scheduled for Roux-en-Y gastric bypass
- •Cohorts will be BMI matched
排除标准
- •Antibiotic, liraglutide, or methotrexate usage within two months preceding enrollment
- •Meal replacement use within one month
- •Previous bowel resection
- •Inflammatory bowel disease
- •Previous bariatric surgery
结局指标
主要结局
Fecal microbial analysis
时间窗: 9 month post intervention
The microbial community composition of fecal samples will be assessed using 16S rRNA gene analyses
次要结局
- Serum metabolomics(9 month post intervention)
- Urine metabolomics(9 month post intervention)
- Serum Inflammatory cytokines and chemokines(9 month post intervention)
- Tissue Inflammatory cytokines and chemokines(same day of surgery)
研究者
Daniel Birch
MSc, MD, FRCSC, FACS, CAMIS Medical Director, Professor of Surgery
University of Alberta