title: Effect of prebiotic intake on gut microbiota, intestinal permeability and glycemic control in children with type 1 diabetes: study protocol for a randomized controlled trial.
abstract: The gut microbiome is increasingly recognized as a contributor to disease states. Patients with type 1 diabetes (DM1) have distinct gut microbiota in comparison to non-diabetic individuals, and it has been linked to changes in intestinal permeability, inflammation and insulin resistance. Prebiotics are non-digestible carbohydrates that alter gut microbiota and could potentially improve glycemic control in children with DM1. This pilot study aims to determine the feasibility of a 12-week dietary intervention with prebiotics in children with DM1.
  
  
  
  This pilot study is a single-centre, randomized, double-blind, placebo-controlled trial in children aged 8 to 17 years with DM1 for at least one year. Participants will be randomized to receive either placebo (maltodextrin 3.3 g orally/day) or prebiotics (oligofructose-enriched inulin 8 g orally/day; Synergy1, Beneo, Mannheim, Germany). Measures to be assessed at baseline, 3 months and 6 months include: anthropometric measures, insulin doses/regimens, frequency of diabetic ketoacidosis, frequency of severe hypoglycemia, average number of episodes of hypoglycemia per week, serum C-peptide, HbA1c, serum inflammatory markers (IL-6, IFN-gamma, TNF-alpha, and IL-10), GLP-1 and GLP-2, intestinal permeability using urine assessment after ingestion of lactulose, mannitol and 3-O-methylglucose, and stool sample collection for gut microbiota profiling.
  
  
  
  This is a novel pilot study designed to test feasibility for a fully powered study. We hypothesize that consumption of prebiotics will alter gut microbiota and intestinal permeability, leading to improved glycemic control. Prebiotics are a potentially novel, inexpensive, low-risk treatment addition for DM1 that may improve glycemic control by changes in gut microbiota, gut permeability and inflammation.
  
  
  
  ClinicalTrials.gov: NCT02442544 . Registered on 10 March 2015.
authors.affiliation: Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, T3B 6A8, Canada.
authors.forename: Josephine
authors.initials: J
authors.lastname: Ho
authors.affiliation: Faculty of Kinesiology, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Raylene A
authors.initials: RA
authors.lastname: Reimer
authors.affiliation: Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, T3B 6A8, Canada.
authors.forename: Manpreet
authors.initials: M
authors.lastname: Doulla
authors.affiliation: Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, T3B 6A8, Canada. carol.huang@ahs.ca.
authors.forename: Carol
authors.initials: C
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000416:Alberta; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D002985:Clinical Protocols; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D007444:Inulin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000009:adverse effects; D010539:Permeability; D010865:Pilot Projects; D056692:Prebiotics / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D009844:Oligosaccharides; D056692:Prebiotics; C120489:oligofructose; D007444:Inulin
keywords: Child; Gut microbiota; Intestinal permeability; Prebiotics; Type 1 diabetes