The Effect of PPI Therapy on Weight, Gut Microbiome, and Expression of GPR41 and GPR43
试验速览
- 阶段
- 不适用
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Gut microbiota
研究概览
简要总结
The investigators long-term goal is to understand how PPIs influence energy balance in both obese and normal-weight individuals. The overall goal of this study is to determine whether PPI use causes detrimental changes in the composition and functional properties of the gut microbiome, and whether any such effects are mediated by altered responses of human fatty acid receptors (e.g., GPR41/43).
详细描述
Research Plan:
Patients without gastrointestinal symptoms scheduled for a screening or surveillance colonoscopy (for colorectal cancer) at the UCH endoscopy lab will be screened for the study based on the inclusion and exclusion criteria. Eligible patients who consent to the study will have height, weight, and demographic information measured and recorded. They will complete a weight/diet history questionnaire. Patients will undergo the screening/surveillance colonoscopy per routine clinical care. Residual stool is standardly aspirated through the colonoscope to ensure full visualization of the mucosa to enhance polyp detection. We will take stool aspirates from three separate locations: sigmoid colon, cecum, and terminal ileum. Evidence suggests that a bowel preparation (prior to colonoscopy) does not significantly change the composition of the intestinal microbiota for the majority of subjects. We will also take four small, pinch biopsies at each of these three sites. Stool aspirates and biopsy specimens will be snap-frozen in liquid N2 and frozen at -80C until required for their assays.
We will enroll a total of 48 subjects divided equally between four groups: OB/PPI, OB/non-PPI, NW/PPI, and NW/non-PPI. Approximately 40-50 patients per week meeting the above inclusion/exclusion criteria undergo a screening/surveillance colonoscopy at UCH, making recruitment of 2-3 patients/week over 6-9 months realistic to reach targeted enrollment.
Aim 1: To examine the effects of PPI use on the gut microbiota in the colon and terminal ileum of normal-weight (NW) and obese (OB) patients. Intestinal microbiomes will be profiled by 16S rRNA sequencing to identify PPI-associated alterations in gut biodiversity.
Separate sterile specimen collection containers will be used for the stool aspirates and mucosal biopsies from the sigmoid colon, cecum, and terminal ileum. High-throughput DNA sequencing for microbiome analysis will be used.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •asymptomatic (no complaints of abdominal pain, diarrhea, blood in stools, constipation, etc.)
- •age 40-59 years
- •PPI users (Use of a PPI for ≥ 4 days/week for the preceding 8 weeks) or non-users of acid suppressing medications (no use of a PPI or H2B for the previous 8 weeks)
- •BMI that is either normal-weight (BMI of 18.5-<25 kg/m2) or Class I/ II obese (BMI of 30-<40 kg/m2).
排除标准
- •probiotic or antibiotic use within 3 months of the colonoscopy
- •inflammatory bowel disease
- •personal history of colon cancer
- •resection of any portion of the gastrointestinal tract (including appendectomy and cholecystectomy)
- •Significant motility disorders of the GI tract (e.g., gastroparesis, colonic inertia)
- •Use of immunosuppressive medications within the past 6 months
- •pregnancy/lactation
- •HIV or other immune deficiencies
结局指标
主要结局
Gut microbiota
时间窗: Within 3 months of colonoscopy
The primary aim of this study is to examine the effect of PPI therapy on the gut microbiota in the colon and terminal ileum of normal weight and obese patients.
次要结局
- Gut bacterial RNA dedicated to the fermentation cycle(within 3 month of colonoscopy.)