title: 11β-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet.
abstract: The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) interconverts active glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme, 11β-HSD1, predominantly reactivates glucocorticoids in vivo and can also metabolise bile acids. 11β-HSD1-deficient mice show altered inflammatory responses and are protected against the adverse metabolic effects of a high-fat diet. However, the impact of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterise the gut microbiome of 11β-HSD1-deficient and C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat-enriched 'Western' diet. 11β-HSD1 deficiency significantly altered the composition of the gut microbiome, and did so in a diet-specific manner. On a Western diet, 11β-HSD1 deficiency increased the relative abundance of the family Bacteroidaceae, and on a chow diet, it altered relative abundance of the family Prevotellaceae Our results demonstrate that (i) genetic effects on host-microbiome interactions can depend upon diet and (ii) that alterations in the composition of the gut microbiome may contribute to the aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1 deficiency.
authors.affiliation: Computational Genomics Analysis and TrainingMedical Research Council-Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors.forename: Jethro S
authors.initials: JS
authors.lastname: Johnson
authors.affiliation: University/BHF Centre for Cardiovascular ScienceQueen's Medical Research Institute, Edinburgh, UK.
authors.forename: Monica N
authors.initials: MN
authors.lastname: Opiyo
authors.affiliation: Edinburgh GenomicsAshworth Laboratories, University of Edinburgh, Edinburgh, UK.
authors.forename: Marian
authors.initials: M
authors.lastname: Thomson
authors.affiliation: Edinburgh GenomicsAshworth Laboratories, University of Edinburgh, Edinburgh, UK.
authors.forename: Karim
authors.initials: K
authors.lastname: Gharbi
authors.affiliation: University/BHF Centre for Cardiovascular ScienceQueen's Medical Research Institute, Edinburgh, UK.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.affiliation: Computational Genomics Analysis and TrainingMedical Research Council-Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heger
authors.affiliation: University/BHF Centre for Cardiovascular ScienceQueen's Medical Research Institute, Edinburgh, UK karen.chapman@ed.ac.uk.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Chapman
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001438:Bacteroidaceae / Q000302:isolation & purification*; D002432:Cecum / Q000378:metabolism / Q000382:microbiology*; D003106:Colon / Q000378:metabolism / Q000382:microbiology*; D066273:Diet, Western; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1
keywords: 11β-HSD; diet; glucocorticoids; gut microbiome