title: Host-microbiome interactions in human type 2 diabetes following prebiotic fibre (galacto-oligosaccharide) intake.
abstract: Aberrant microbiota composition and function have been linked to several pathologies, including type 2 diabetes. In animal models, prebiotics induce favourable changes in the intestinal microbiota, intestinal permeability (IP) and endotoxaemia, which are linked to concurrent improvement in glucose tolerance. This is the first study to investigate the link between IP, glucose tolerance and intestinal bacteria in human type 2 diabetes. In all, twenty-nine men with well-controlled type 2 diabetes were randomised to a prebiotic (galacto-oligosaccharide mixture) or placebo (maltodextrin) supplement (5·5 g/d for 12 weeks). Intestinal microbial community structure, IP, endotoxaemia, inflammatory markers and glucose tolerance were assessed at baseline and post intervention. IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin-modified intravenous glucose tolerance test. Intestinal microbial community analysis was performed by high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR. Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo; however, changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels (r -0·90, P=0·042 for both) following prebiotic intake. The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding. We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role. The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes.
authors.affiliation: 1Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
authors.forename: Camilla
authors.initials: C
authors.lastname: Pedersen
authors.affiliation: 2Medical Physics - Nuclear Medicine,Royal Surrey County Hospital, Guildford GU2 7XX,UK.
authors.forename: Edith
authors.initials: E
authors.lastname: Gallagher
authors.affiliation: 2Medical Physics - Nuclear Medicine,Royal Surrey County Hospital, Guildford GU2 7XX,UK.
authors.forename: Felicity
authors.initials: F
authors.lastname: Horton
authors.affiliation: 3Animal and Plant Health Agency,Addlestone KT15 3NB,UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: 4School of Engineering,University of Glasgow, Glasgow G12 8LT,UK.
authors.forename: Umer Z
authors.initials: UZ
authors.lastname: Ijaz
authors.affiliation: 1Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
authors.forename: Huihai
authors.initials: H
authors.lastname: Wu
authors.affiliation: 1Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
authors.forename: Etana
authors.initials: E
authors.lastname: Jaiyeola
authors.affiliation: 1Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
authors.forename: Onyinye
authors.initials: O
authors.lastname: Diribe
authors.affiliation: 5Louvain Drug Research Institute,Catholic University of Louvain, Brussels B-1200,Belgium.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Duparc
authors.affiliation: 5Louvain Drug Research Institute,Catholic University of Louvain, Brussels B-1200,Belgium.
authors.forename: Patrice D
authors.identifier: http://orcid.org/0000-0003-2040-2448
authors.initials: PD
authors.lastname: Cani
authors.affiliation: 6Department of Food and Nutritional Sciences,University of Reading, Reading RG6 6AP,UK.
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gibson
authors.affiliation: 2Medical Physics - Nuclear Medicine,Royal Surrey County Hospital, Guildford GU2 7XX,UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Hinton
authors.affiliation: 1Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.affiliation: 1Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
authors.forename: Roberto
authors.initials: R
authors.lastname: La Ragione
authors.affiliation: 1Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
authors.forename: M Denise
authors.initials: MD
authors.lastname: Robertson
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D004311:Double-Blind Method; D064806:Dysbiosis / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism / Q000382:microbiology; D019446:Endotoxemia / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D005500:Follow-Up Studies; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008131:London; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D056692:Prebiotics; D014312:Trisaccharides / Q000627:therapeutic use*; D045854:Veillonellaceae / Q000187:drug effects / Q000254:growth & development / Q000276:immunology / Q000502:physiology
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D056692:Prebiotics; D014312:Trisaccharides; C072242:4'-galactooligosaccharide; D008687:Metformin
keywords:  GOS galacto-oligosaccharide;  IP intestinal permeability;  LPS lipopolysaccharide;  T2D type 2 diabetes;  qPCR quantitative real-time PCR; Diabetes; Endotoxaemia; Gut microbiota; Intestinal permeability; Prebiotic supplements