11β-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to western diet

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 influence of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterize 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 aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1-deficiency.