Intestinal Microbiota and NAFLD Pre and Post Bariatric Surgery

NCT01856465 | Unknown

• 1 other identifier: 13-6115-A
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) includes benign hepatic simple steatosis (SS) and steatohepatitis (NASH), which is characterised by inflammation leading to fibrosis and cirrhosis. NAFLD is the hepatic manifestation of the metabolic syndrome, and the prevalence is 74-98% in morbidly obese individuals undergoing bariatric surgery. Although steatosis improves post bariatric surgery, hepatic inflammation and fibrosis do not consistently improve. Alterations of the human gut flora (intestinal microbiota; IM) may play a role. One mechanism linking IM to obesity, insulin resistance (IR), and NAFLD is through translocation of bacterial lipopolisaccharide (LPS=endotoxin) into the blood stream (=endotoxemia), causing chronic inflammation. Morbidly obese subjects have different IM compared to lean controls, and the IM structure is significantly altered after bariatric surgery, probably due to a combination of anatomic changes, diet, and weight loss. For example, the ratio of Firmicutes/Bacteroidetes may be lower in obese subjects compared to lean controls and lower numbers of Faecalibacterium prausnitzii were reported in some obese subjects before bariatric surgery, which increased 3 months post-surgery. This is of interest since, in animal studies, low abundance of F. prausnitzii, a butyrate producing bacterium, is associated with increased intestinal permeability, endotoxemia, and inflammation. To our knowledge, only two studies are available describing IM in patients pre and post bariatric surgery, and no data have been published on the relationship between IM and NAFLD in these patients.

Conditions

Morbid Obesity; Non-alcoholic Fatty Liver Disease

Keywords

Bariatric surgery; NAFLD; Steatohepatitis; Simple Steatosis; Intestinal Microbiota

Outcome Measures

Primary Outcomes (1)

• Firmicutes/Bacteroides ratio in feces

  16S rRNA sequencing will be performed on the Ion Torrent platform

  Baseline, 6, 12 months

Secondary Outcomes (4)

• Overall microbiota composition, amount of selected groups of microorganisms and concentration of Short Chain Fatty Acid (SCFA) in stool sample

  8 months

• The amount of endotoxin, TNF-alfa and IL-6 in plasma/serum

  8 months

• The change in inflammation, fibrosis, steatosis in liver histology

  12 months

• NAFLD activity score

  baseline, 12 months

Study Arms (1)

Bariatric surgery of morbid obese

Morbid obese patient who undergo Bariatric surgery with NAFLD (NASH or SS) status

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

NAFLD is the hepatic manifestation of the metabolic syndrome, and the prevalence is 74-98% in morbidly obese individuals. The aim of this study is to examine the role of intestinal microbiota (IM) in non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Alterations of the human gut flora (intestinal microbiota) will be determined before and after surgery in realtion with the change of liver histology.

You may qualify if:

• BMI\>40 kg/m2 or BMI\>35-40 kg/m2 with severe weight loss comorbidities
• Male or female, equal or over 18 years of age
• Alcohol consumption is leass than 20 g/d

You may not qualify if:

• No diagnosis of NAFLD
• Having liver disease of other etiology
• Having advance liver disease
• Having abnormal coagulation or other reason contraindicating a Liver Biopsy
• On medication known to precipitate steatohepatitis 6 months prior to entry
• On regular intake of non-steroidal anti-inflammatory drugs, prebiotics, probiotics and antibiotics, ursodeoxycholic or any experimental drug in the 3 months prior to study entry
• Having type-1 diabetes, chronic gastrointestinal diseases, previous gastrointestinal surgery modifying the anatomy (prior to bariatric surgery)
• Smoking
• Pregnancy or Breastfeeding

Sponsors & Collaborators

• Johane Allard: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (12)

• Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, McGilvray ID, Allard JP. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013 Jul;58(1):120-7. doi: 10.1002/hep.26319. Epub 2013 May 14.

  PMID: 23401313 BACKGROUND

• Musso G, Gambino R, Cassader M. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Prog Lipid Res. 2009 Jan;48(1):1-26. doi: 10.1016/j.plipres.2008.08.001. Epub 2008 Sep 9.

  PMID: 18824034 BACKGROUND

• Bellentani S, Scaglioni F, Marino M, Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig Dis. 2010;28(1):155-61. doi: 10.1159/000282080. Epub 2010 May 7.

  PMID: 20460905 BACKGROUND

• Mathurin P, Hollebecque A, Arnalsteen L, Buob D, Leteurtre E, Caiazzo R, Pigeyre M, Verkindt H, Dharancy S, Louvet A, Romon M, Pattou F. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology. 2009 Aug;137(2):532-40. doi: 10.1053/j.gastro.2009.04.052. Epub 2009 May 4.

  PMID: 19409898 BACKGROUND

• Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2557-62. doi: 10.1073/pnas.94.6.2557.

  PMID: 9122234 BACKGROUND

• da Silva VR, Moreira EA, Wilhelm-Filho D, de Miranda JX, Beninca JP, Vigil SV, Moratelli AM, Garlet TR, de Souza Meirelles MS, Vannucchi H, Frode TS. Proinflammatory and oxidative stress markers in patients submitted to Roux-en-Y gastric bypass after 1 year of follow-up. Eur J Clin Nutr. 2012 Aug;66(8):891-9. doi: 10.1038/ejcn.2012.17. Epub 2012 Feb 22.

  PMID: 22353926 BACKGROUND

• Musso G, Gambino R, Cassader M. Emerging molecular targets for the treatment of nonalcoholic fatty liver disease. Annu Rev Med. 2010;61:375-92. doi: 10.1146/annurev.med.60.101107.134820.

  PMID: 20059344 BACKGROUND

• Frazier TH, DiBaise JK, McClain CJ. Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury. JPEN J Parenter Enteral Nutr. 2011 Sep;35(5 Suppl):14S-20S. doi: 10.1177/0148607111413772. Epub 2011 Aug 1.

  PMID: 21807932 BACKGROUND

• Spencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology. 2011 Mar;140(3):976-86. doi: 10.1053/j.gastro.2010.11.049. Epub 2010 Dec 1.

  PMID: 21129376 BACKGROUND

• Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3. doi: 10.1038/4441022a.

  PMID: 17183309 BACKGROUND

• Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31. doi: 10.1038/nature05414.

  PMID: 17183312 BACKGROUND

• Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007 Feb;73(4):1073-8. doi: 10.1128/AEM.02340-06. Epub 2006 Dec 22.

  PMID: 17189447 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Liver biopsy and stool samples

MeSH Terms

Conditions

Obesity, Morbid; Non-alcoholic Fatty Liver Disease; Fatty Liver

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases

Study Officials

• Johane Allard, MD. FRCPC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Gastroenterologist

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 17, 2013
• Study Start: June 1, 2013
• Primary Completion: June 30, 2022
• Study Completion: August 30, 2023
• Last Updated: November 2, 2022

Record last verified: 2022-11

Locations

CA (1)