NCT01856465|Unknown
Intestinal Microbiota and NAFLD Pre and Post Bariatric Surgery
Role of Intestinal Microbiota in Non-alcoholic Fatty Liver Disease Pre and Post bAriatric Surgery
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Role of Intestinal Microbiota in Non-alcoholic Fatty Liver Disease Pre and Post bAriatric Surgery
Sponsor study identifier
observational
120
1 country
1
Study Start
June 2013
Actual (reported)Primary Completion
June 30, 2022
Actual (reported)Study Completion
August 30, 2023
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
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.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
August 30, 2023
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
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Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
May 14, 2013
Actual (reported)May 17, 2013
Actual (reported)June 2013
Actual (reported)June 30, 2022
Actual (reported)August 30, 2023
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
Firmicutes/Bacteroides ratio in feces
16S rRNA sequencing will be performed on the Ion Torrent platform
Baseline, 6, 12 months
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
Morbid obese patient who undergo Bariatric surgery with NAFLD (NASH or SS) status
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.
University Health Network
Toronto, Ontario, M5G 2C4, Canada
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.
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.
Liver biopsy and stool samples
Johane Allard, MD. FRCPC
University Health Network, Toronto
First Submitted
May 14, 2013
First Posted
May 17, 2013
Study Start
June 2013
Actual (reported)Primary Completion
June 30, 2022
Actual (reported)Fatty Liver Patient Registry
Contact the study team to confirm eligibility.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Study Completion
August 30, 2023
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
Last Updated
November 2, 2022
Record last verified: 2022-11
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