Mode of Action of Butyrate in the Human Colon
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 试验地点
- 2
- 主要终点
- Colonic permeability ex vivo in Ussing chambers
研究概览
简要总结
Butyrate has recently gained attention as an important microbial compound in human colon health. Several diseases, including Irritable Bowel Syndrome (IBS), have been linked with a loss of butyrate in the colon resulting in the hypothesis that butyrate is important for disease resistance. However, despite a plethora of preclinical evidence about butyrate's role in colon health, data from human studies are insufficient, largely due to the lack of available tools for colon-specific butyrate delivery and sampling. This project will elucidate butyrate's mode of action in the human colon and its implications for gut functioning in IBS and healthy participants by employing a unique in vivo human setting. Specifically, the regulatory capacity of butyrate on intestinal barrier function and the transcriptional host responses that are associated with an increase of butyrate in the colon will be determined. Moreover, butyrate's role as a signalling molecule for gut hormones and serotonin release will be studied.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •signed informed consent
- •Fulfilled Rome IV diagnostic criteria for IBS (for IBS participants)
排除标准
- •known gastrointestinal diseases
- •previous complicated gastrointestinal surgery (including e.g. appendectomy or cholecystectomy)
- •pregnancy or breast-feeding
- •use of antibiotics within the last 12 weeks before the colonoscopy procedure
- •regular consumption of probiotics within the last 4 weeks before the colonoscopy procedure
- •use of laxatives or anti-diarrhoeals within the last 4 weeks before the colonoscopy procedure
- •use of serotonin selective re-uptake inhibitors (SSRI) or serotonin nor-epinephrine re-uptake inhibitors (SNRI) with the last 12 weeks before the colonoscopy procedure
- •alcohol or drug abuse
- •latex allergy
- •any other clinically significant disease/condition which in the investigator's opinion could interfere with the results of the study.
结局指标
主要结局
Colonic permeability ex vivo in Ussing chambers
时间窗: Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution
Difference in the translocation of FITC-labeled dextran and horseradish peroxidase between the study arms before and after exposure to the butyrate bolus
次要结局
- Concentrations of blood peptide YY (PYY)(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Regulation of gene expression(Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution)
- Concentrations of blood gastric inhibitory polypeptide (GIP)(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Concentrations of blood insulin(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Concentrations of blood serotonin(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Butyrate uptake ex vivo in Ussing chambers(Mucosal biopsies collected pre- and 90 min post-administration of the butyrate solution)
- Concentrations of blood glucose(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Concentrations of blood metabolites in the gluconeogenic pathway(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Concentrations of blood glucagon like peptide-1 (GLP-1)(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Concentrations of blood glucagon like peptide-2 (GLP-2)(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Concentrations of blood glucagon(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Concentrations of blood leptin(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
- Concentrations of blood butyrate(Blood samples collected before (0 min) and at six timepoints after the butyrate solution administration (5, 15, 30, 45, 60 and 90 min).)
研究者
Robert Brummer
Professor
Örebro University, Sweden