title: Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol.
abstract: BACKGROUND
  Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD.
  
  
  METHODS
  In a double blind, placebo controlled, parallel group study, adults (BMI ≥25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks (n = 30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated.
  
  
  CONCLUSIONS
  There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted.
  
  
  BACKGROUND
  ClinicalTrials.gov (NCT02568605) Registered 30 September 2015.
authors.affiliation: Faculty of Kinesiology, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada. jlambert@ucalgary.ca.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Lambert
authors.affiliation: Health and Physical Education, Mount Royal University, 4825 Mount Royal Gate SW, Calgary, AB, T3E 6K6, Canada. jparnell@mtroyal.ca.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Parnell
authors.affiliation: Snyder Institute for Chronic Diseases, Health Research and Innovation Center, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. b.eksteen@ucalgary.ca.|Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. b.eksteen@ucalgary.ca.
authors.forename: Bertus
authors.initials: B
authors.lastname: Eksteen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. mkothand@ucalgary.ca.
authors.forename: Maitreyi
authors.initials: M
authors.lastname: Raman
authors.affiliation: Faculty of Kinesiology, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada. mrbomhof@ucalgary.ca.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Bomhof
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. kprioux@ucalgary.ca.|Department of Microbiology and Infectious Diseases, University of Calgary, 1863 Health Sciences Centre, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. kprioux@ucalgary.ca.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Rioux
authors.affiliation: Division of Gastroenterology, Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, 7-142 Katz Group-Rexall Centre, University of Alberta, Edmonton, AB, T6G 2C2, Canada. karen.madsen@ualberta.ca.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Madsen
authors.affiliation: Faculty of Kinesiology, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada. reimer@ucalgary.ca.|Department of Biochemistry & Molecular Biology, Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. reimer@ucalgary.ca.
authors.forename: Raylene A
authors.initials: RA
authors.lastname: Reimer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002985:Clinical Protocols; D019587:Dietary Supplements / Q000382:microbiology; D004311:Double-Blind Method; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D050155:Lipogenesis; D008099:Liver / Q000382:microbiology; D008103:Liver Cirrhosis / Q000209:etiology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000382:microbiology / Q000628:therapy*; D056692:Prebiotics / Q000008:administration & dosage*; D015431:Weight Loss; D055815:Young Adult
chemical_list: D056692:Prebiotics