Abstract 15581: Absence of Intestinal Microbiota Increases Beta-cyclodextrin Stimulated Reverse Cholesterol Transport
Background: Atherosclerotic cardiovascular disease (CVD) represents the highest cause of mortality worldwide. Currently drug treatment with statins is the main stay of therapy to prevent heart attacks and stroke. However, despite the vast use of statins, the incidence of CVD events decreased at best by only 30%. Therefore, additional therapeutic strategies are warranted. Dietary intervention appears hereby particularly attractive, since it is easy and increases adherence to the treatment.
Aim: The aim of the present study was to characterize the impact of dietary ß-cyclodextrin (ßCD, 10%), a cyclic oligosaccharide, on sterol metabolism and reverse cholesterol transport (RCT) in conventional as well as germ-free mice. Germ-free mice were included to establish whether fermentation products of ßCD by the intestinal microbiota contribute to the biological effects of this non-digestible carbohydrate.
Method and Results: In conventional ßCD-fed C57BL/6 wild-type mice plasma cholesterol levels decreased significantly (-40%, p < 0.05), while fecal neutral sterol excretion increased (3-fold, p < 0.01) and fecal bile acid excretion was unchanged. Hepatic cholesterol levels and biliary cholesterol secretion were unaltered. Changes in cholesterol metabolism translated into increased macrophage-to-feces RCT in ßCD-administered mice (1.5-fold, p < 0.05). In germ-free C57BL/6 mice ßCD similarly lowered plasma cholesterol (-40%, p < 0.05). However, fecal neutral sterol excretion (7.5-fold, p < 0.01), bile acid excretion (2-fold, p < 0.05) and RCT (2.5-fold, p < 0.01) showed an even more substantial increase on the ßCD diet than in conventional mice upon ßCD feeding.
Conclusion: In summary, this study demonstrates that ßCD lowers plasma cholesterol levels and increases fecal cholesterol excretion from a RCT-relevant pool independent of bacterial metabolism in the intestine. The metabolic effects of dietary ßCD are expected to translate into cardiovascular health benefits.
Author Disclosures: R.H. Mistry: None. H.J. Verkade: None. U.J. Tietge: None.
- © 2016 by American Heart Association, Inc.