Transplantation of Microbes for Treatment of Metabolic Syndrome & NAFLD

Summary

Non-alcoholic fatty liver disease (NAFLD) occurs when excess fat is deposited in the liver. Almost all patients also have obesity and insulin resistance (the inability of the body to effectively use insulin). Obesity and NAFLD are intricately intertwined and are increasing in incidence. While weight loss is the most effective therapy for NAFLD, the investigators' efforts are failing and in the next generation it will become the most common cause of liver failure in Canada. Recently, researchers have focused on the potential use of altering the composition of bacteria in the gut (microbiome) to alter absorption of energy from food, deposition of fat and resistance to insulin. This study will determine if transplantation of bacteria from the stool of a healthy volunteer into an individual with metabolic syndrome and NAFLD (i.e. fecal microbiota transplant/FMT) can alter insulin resistance and reduce the amount of fat deposited in the liver. FMT is being studied to treat several clinical conditions and is now standard of care for the treatment of refractory Clostridium difficile infection. Investigators are proposing a randomized controlled pilot study of FMT in 21 patients to determine the feasibility and to inform us of changes needed for a larger study.

Timeline

Start

2016-06

Primary completion

2018-04

Completion

2018-12

Publications

• Background Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieuwdorp M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012 Oct;143(4):913-6.e7. doi: 10.1053/j.gastro.2012.06.031. Epub 2012 Jun 20.
• Background van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.
• Background Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012 May;107(5):761-7. doi: 10.1038/ajg.2011.482. Epub 2012 Jan 31.
• Background Kunde S, Pham A, Bonczyk S, Crumb T, Duba M, Conrad H Jr, Cloney D, Kugathasan S. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr. 2013 Jun;56(6):597-601. doi: 10.1097/MPG.0b013e318292fa0d.
• Background Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr. 2014 Nov;168(11):1063-9. doi: 10.1001/jamapediatrics.2014.1539.
• Aghara H, Patel M, Chadha P, Parwani K, Chaturvedi R, Mandal P. Unraveling the Gut-Liver-Brain Axis: Microbiome, Inflammation, and Emerging Therapeutic Approaches. Mediators Inflamm. 2025 Jun 18;2025:6733477. doi: 10.1155/mi/6733477. eCollection 2025.
• Craven L, Rahman A, Nair Parvathy S, Beaton M, Silverman J, Qumosani K, Hramiak I, Hegele R, Joy T, Meddings J, Urquhart B, Harvie R, McKenzie C, Summers K, Reid G, Burton JP, Silverman M. Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial. Am J Gastroenterol. 2020 Jul;115(7):1055-1065. doi: 10.14309/ajg.0000000000000661.

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