TY - JOUR
T1 - Allogenic Fecal Microbiota Transplantation in Patients with Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability
T2 - A Randomized Control Trial
AU - Craven, Laura
AU - Rahman, Adam
AU - Nair Parvathy, Seema
AU - Beaton, Melanie
AU - Silverman, Justin
AU - Qumosani, Karim
AU - Hramiak, Irene
AU - Hegele, Rob
AU - Joy, Tisha
AU - Meddings, Jon
AU - Urquhart, Brad
AU - Harvie, Ruth
AU - McKenzie, Charles
AU - Summers, Kelly
AU - Reid, Gregor
AU - Burton, Jeremy P.
AU - Silverman, Michael
N1 - Funding Information:
We would like to thank Academic Medical Organization of Southwestern Ontario (AMOSO) Innovation Fund for the support for this work; Ms. Brenda Done and Ms. Kelly Muhsin for support in screening donors; Prof. Yves Bureau, Department of Biostatistics for carrying out the statistical analysis; Mr. Kim P. Lee, Research Assistant, University of Calgary, for HPLC analysis of the urine samples; Dr. Subrata Chakrabarti for reviewing NAFLD biopsies. We would also like to thank the FMT donors and patients; Ms. Shannon Seney, Laboratory Manager, Lawson Research Institute; Mr. David Reese, MRI Technologist, Robarts Research Institute; Ms. Mala Ramu from Centre for Clinical Investigations and Therapeutics (CCIT); Dr. Susana Pearl for editing.
Funding Information:
Guarantor of article: Michael Silverman, MD. Specific author contributions: L.C.: Study design, Microbiome analysis, drafting the manuscript. A.R.: Study design, performance of FMT’s. S.N.P.: Study design, FMT preparation, and donor screening. M.B.: Study design, patient assessment, and review of the manuscript. J.S.: Microbiome analysis and review of the manuscript. K.Q.: Patient assessment and review of the manuscript. I.H.: Study design and review of the manuscript. R.H.: Study design and review of the manuscript. T.J.: Study design and review of manuscript. J.M.: Study design, review of manuscript, and performance of permeability assays. B.U.: Study design and review of the manuscript. R.H.: Study design, and analysis of the Food Questionnaire results. C.M.: Study design, review of the manuscript, and analysis of the PDFF data. K.S.: Study design and review of the manuscript. G.R.: Study design and review of the manuscript. J.P.B.: Study design, review of the manuscript, and microbiome analysis. M.S.: Study design and supervision and manuscript writing. Financial support: This study was funded by AMOSO. This work was conducted independently of AMOSO. Potential competing interests: None to declare. Clinical Trials Number: NCT02496390.
Publisher Copyright:
© 2020 by The American College of Gastroenterology.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
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U2 - 10.14309/ajg.0000000000000661
DO - 10.14309/ajg.0000000000000661
M3 - Article
C2 - 32427675
AN - SCOPUS:85087471680
VL - 115
SP - 1055
EP - 1065
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
SN - 0002-9270
IS - 7
ER -