Investigation on Novel Route of Gut Microbiota Products for Bariatric Surgery to Improve Non-alcoholic Steatohepatitis and Development on Therapeutic Implications

  • STATUS
    Recruiting
  • End date
    Sep 1, 2024
  • participants needed
    140
  • sponsor
    National Taiwan University Hospital
Updated on 15 October 2022
diabetes
liver cancer
cancer
chronic disease
liver disease
microbiota
fatty liver
steatosis
fibrosis
bariatric surgery
steatohepatitis
Accepts healthy volunteers

Summary

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.

Description

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.

  1. 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.
  2. 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)

Details
Condition Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steatohepatitis, Bariatric Surgery
Treatment Bariatric Surgery
Clinical Study IdentifierNCT04501042
SponsorNational Taiwan University Hospital
Last Modified on15 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age >20,morbidly obese patients who will receive bariatric surgery

Exclusion Criteria

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
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