title: Characterization of the gut microbiota in leptin deficient obese mice - Correlation to inflammatory and diabetic parameters.
abstract: Gut microbiota have been implicated as a relevant factor in the development of type 2 diabetes mellitus (T2DM), and its diversity might be a cause of variation in animal models of T2DM. In this study, we aimed to characterise the gut microbiota of a T2DM mouse model with a long term vision of being able to target the gut microbiota to reduce the number of animals used in experiments. Male B6.V-Lep(ob)/J mice were characterized according to a number of characteristics related to T2DM, inflammation and gut microbiota. All findings were thereafter correlated to one another in a linear regression model. The total gut microbiota profile correlated to glycated haemoglobin, and high proportions of Prevotellaceae and Lachnospiraceae correlated to impaired or improved glucose intolerance, respectively. In addition, Akkermansia muciniphila disappeared with age as glucose intolerance worsened. A high proportion of regulatory T cells correlated to the gut microbiota and improved glucose tolerance. Furthermore, high levels of IL-10, IL-12 and TNF-α correlated to impaired glucose tolerance, blood glucose or glycated haemoglobin. The findings indicate that gut microbiota may contribute to variation in various disease read-outs in the B6.V-Lep(ob)/J model and considering them in both quality assurance and data evaluation for the B6.V-Lep(ob)/J model may have a reducing impact on the inter-individual variation.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 18, DK-1870 Frederiksberg C, Denmark. Electronic address: mell@sund.ku.dk.
authors.forename: M
authors.initials: M
authors.lastname: Ellekilde
authors.affiliation: Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Krych
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 18, DK-1870 Frederiksberg C, Denmark.
authors.forename: C H F
authors.initials: CH
authors.lastname: Hansen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 18, DK-1870 Frederiksberg C, Denmark; Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg, Denmark; Centre for Applied Laboratory Animal Research, Scanbur A/S, Silovej 16-18, DK-2690 Karlslunde, Denmark.
authors.forename: M R
authors.initials: MR
authors.lastname: Hufeldt
authors.affiliation: Novo Nordisk, Department of Diabetes and Obesity Pharmacology, Novo Nordisk Park, DK-2760 Måløv, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Dahl
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, 1307 Copenhagen K, Denmark.
authors.forename: L H
authors.initials: LH
authors.lastname: Hansen
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, 1307 Copenhagen K, Denmark.
authors.forename: S J
authors.initials: SJ
authors.lastname: Sørensen
authors.affiliation: Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg, Denmark.
authors.forename: F K
authors.initials: FK
authors.lastname: Vogensen
authors.affiliation: Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg, Denmark.
authors.forename: D S
authors.initials: DS
authors.lastname: Nielsen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 18, DK-1870 Frederiksberg C, Denmark.
authors.forename: A K
authors.initials: AK
authors.lastname: Hansen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000382:microbiology*; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology*; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000276:immunology / Q000382:microbiology*; D007328:Insulin / Q000097:blood; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D064307:Microbiota / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D004269:DNA, Bacterial; D007328:Insulin; D012336:RNA, Ribosomal, 16S
keywords: Glucose intolerance; Gut microbiota; Inflammation; Obesity; Type 2 diabetes