ABCA8 facilitates cholesterol efflux and modulates HDLc levels in humans and mice.

IntroductionWestern diet containing both saturated fat and cholesterol impairs cardio-metabolic health partly by modulating diversity and function of the microbiota. While diet containing only high fat has comparable effects, it is unclear how diets only enriched in cholesterol impact the microbiota. Therefore, we aimed to characterize the response of host and microbiota to a high cholesterol (HC) diet in mice susceptible to cardio-metabolic disease.MethodsLDLR knockout mice received either 1.25% HC or no cholesterol containing control diet (NC) for 12 weeks before characterizing host cholesterol metabolism and intestinal microbiota composition (next generation sequencing).ResultsHC diet substantially increased plasma (1.6-fold) and liver cholesterol levels (21-fold), biliary cholesterol secretion (4.5-fold) and fecal neutral sterol excretion (68-fold, each p < 0.001) but not fecal bile acid excretion. Interestingly, despite the profound changes in intestinal cholesterol homeostasis no differences in microbial composition between control and HC-fed mice were detected. In both groups the main phyla were Bacteroidetes (55%), Firmicutes (27%) and Verrucomicrobia (14%).ConclusionOur results demonstrate that in mice HC diet alone does not alter the microbiota composition despite inducing substantial adaptive changes in whole body cholesterol homeostasis. The impact of Western diet on intestinal microbiota thus appears to be mediated exclusively by its high fat content.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-017-0170-x) contains supplementary material, which is available to authorized users.