Allogenic Fecal Microbiota Transplantation in Patients with Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial

Authors

Laura Craven, The University of Western Ontario
Adam Rahman, Lawson Health Research Institute
Seema Nair Parvathy, St. Joseph's Health Care London
Melanie Beaton, Lawson Health Research Institute
Justin Silverman, Duke University
Karim Qumosani, Lawson Health Research Institute
Irene Hramiak, Lawson Health Research Institute
Rob Hegele, Lawson Health Research Institute
Tisha Joy, Lawson Health Research Institute
Jon Meddings, University of Calgary
Brad Urquhart, Lawson Health Research Institute
Ruth Harvie, Canadian Centre for Human Microbiome and Probiotics
Charles McKenzie, Lawson Health Research Institute
Kelly Summers, The University of Western Ontario
Gregor Reid, The University of Western Ontario
Jeremy P. Burton, The University of Western Ontario
Michael Silverman, The University of Western Ontario

Document Type

Article

Publication Date

7-1-2020

Journal

American Journal of Gastroenterology

Volume

115

Issue

7

First Page

1055

Last Page

1065

URL with Digital Object Identifier

10.14309/ajg.0000000000000661

Abstract

INTRODUCTION:Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.METHODS:Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.RESULTS:There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.DISCUSSION:FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.