Investigation on Novel Route of Gut Microbiota Products for Bariatric Surgery to Improve Non-alcoholic Steatohepatitis and Development on Therapeutic Implications
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Change of NAFLD severity score (histology) from baseline to the 6th month
研究概览
简要总结
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Non-alcoholic steatohepatitis (NASH) is an aggressive form of NAFLD with remarkable inflammatory features which may cause advanced fibrosis and liver cancer. So far there is no FDA-approved drug for treating NASH. A 10% weight loss by life style modification is a standard recommendation to treat NASH which achieves only 10-20% success rate in clinical practice. Thus, the development of therapeutics to prevent and treat NASH is certainly an unmet need. For now, the mechanism of how simple steatosis progresses to NASH remains unclear and accumulating evidences suggest the role of gut microbiota may be essential. Studies have also noted the bariatric surgery effectively improve diabetes and NASH with significant alterations in the composition and function of gut microbiome. In this study, the investigators aim to investigate the role of gut microbiota in the pathophysiology of NASH by comparing NAFLD severity, gut microbiome, metabolomics, immune profiles among patients before and after the bariatric surgery. With these efforts, the investigators wish to decipher the mechanism of how bariatric surgery may improve NASH through changing the gut microbiota and find out microbe-associated molecular signatures between NASH and NAFLD through this study.
详细描述
The investigators anticipate to recruit 140 morbidly obese patients who will receive bariatric surgery including 100 patients receiving sleeve gastrectomy (SG) and 40 receiving gastric bypass surgery (GB). Liver biopsy will be performed during the operation to confirm the histological scores of NAFLD severity. The investigators expect to have 50% NASH and 50% NAFL patients from these morbidly obese patients based on previous domestic data. (i.e. 50 patients receiving SG to have NASH and 50 patients receiving SG to have NAFL; 20 patients receiving GB to have NASH and 20 patients receiving GB to have NAFL.) In this study, the investigators have two study objectives which are as follows.
- The first objective is to discover potential mechanisms among gut-liver axis for preventing or promoting NAFL to NASH by comparing (1) fecal microbiome composition and metabolomics, (2) peripheral blood biochemistry, metabolomics, immune cell phenotypes, and cytokines (3) portal vein biochemistry, metabolomics, immune cell phenotypes, and cytokines (4) Liver metabolomics and RNA-seq (5) gut permeability test (lactulose/mannitol challenge) (6) host genetic susceptibility for NAFLD (PNPLA3 and TM6SF2) between the tissue-proved NASH and NAFL patients in this study with a cross-sectional comparison.
- The second objective is to longitudinally investigate the potential mechanisms of bariatric surgery for improving NASH via a gut-microbiota dependent pathway. Clinical and experimental data before (baseline) and after (1st, 3rd, 6th months) bariatric surgery will be collected which include (1) non-invasive evaluation of NAFLD severity (Fibroscan, MRI-PDFF (proton density fat fraction) and MRE), (2) blood biochemistry, metabolomics, immune cell phenotypes, and cytokines (3) fecal microbiome and metabolomics (4) gut permeability test (5) liver biopsy histology (if available)
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age >20，morbidly obese patients who will receive bariatric surgery.
排除标准
- •Average daily alcohol intake >20 grams,
- •Hepatitis B carriers, Hepatitis C carriers,
- •people with liver disease caused by other causes
- •liver cirrhosis,
- •diseases related to abnormal blood coagulation,
- •inflammatory bowel disease,
- •routine use of steroids or immunity Inhibitors and other immunomodulatory drugs
- •ursodeoxycholic and other drugs that affect bile acid metabolism
- •those who have used antibiotics or probiotics within one month
结局指标
主要结局
Change of NAFLD severity score (histology) from baseline to the 6th month
时间窗: Baseline and 6 months after bariatric surgery
Liver biopsy will be performed before and after surgery (if available) to acquire histology evaluation
Change of NAFLD severity measured by Fibroscan from baseline to the 6th month
时间窗: Baseline and 6 months after bariatric surgery
Fibroscan (CAP and kPa)
Change of NAFLD severity measured by MRI proton density fat fraction from baseline to the
时间窗: Baseline and 6 months after bariatric surgery
MRI proton density fat fraction (%)
Change of NAFLD severity measured by magnetic resonance elastography from baseline to the
时间窗: Baseline and 6 months after bariatric surgery
magnetic resonance elastography (kPa)
次要结局
- Change of gut microbiome profiles(Baseline, 1st month, 3rd month and 6th month after surgery)
- Change of gene expression profiles of liver tissue(Baseline and 6 months after bariatric surgery (if available))
- Change of metabolomic profiles of liver tissue(Baseline and 6 months after bariatric surgery (if available))
- Change of body fluid metabolomic profiles(Baseline, 1st month, 3rd month and 6th month after surgery)
- Change of Immune profiles(Baseline, 1st month, 3rd month and 6th month after surgery)
- Change of gut permeability test(Baseline and 6 months after bariatric surgery)