Dietary α-cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E-deficient mice

Mol Nutr Food Res. 2017 Aug;61(8):10.1002/mnfr.201600804. doi: 10.1002/mnfr.201600804. Epub 2017 Feb 24.

Abstract

Scope: α-Cyclodextrin (α-CD), a cyclic polymer of glucose, has been shown to lower plasma cholesterol in animals and humans; however, its effect on atherosclerosis has not been previously described.

Methods and results: apoE-knockout mice were fed either low-fat diet (LFD; 5.2% fat, w/w), or Western high fat diet (21.2% fat) containing either no additions (WD), 1.5% α-CD (WDA); 1.5% β-CD (WDB); or 1.5% oligofructose-enriched inulin (WDI). Although plasma lipids were similar after 11 weeks on the WD vs. WDA diets, aortic atherosclerotic lesions were 65% less in mice on WDA compared to WD (P < 0.05), and similar to mice fed the LFD. No effect on atherosclerosis was observed for the other WD supplemented diets. By RNA-seq analysis of 16S rRNA, addition of α-CD to the WD resulted in significantly decreased cecal bacterial counts in genera Clostridium and Turicibacterium, and significantly increased Dehalobacteriaceae. At family level, Comamonadaceae significantly increased and Peptostreptococcaceae showed a negative trend. Several of these bacterial count changes correlated negatively with % atherosclerotic lesion and were associated with increased cecum weight and decreased plasma cholesterol levels.

Conclusion: Addition of α-CD to the diet of apoE-knockout mice decreases atherosclerosis and is associated with changes in the gut flora.

Keywords: Atherosclerosis; Cyclodextrin; Dietary fiber; Gut flora.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / pathology
  • Atherosclerosis / diet therapy*
  • Atherosclerosis / microbiology
  • Atherosclerosis / pathology
  • Body Weight / drug effects
  • Cecum / drug effects
  • Cecum / microbiology
  • Diet, Fat-Restricted
  • Diet, High-Fat / adverse effects
  • Dietary Supplements
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Intestinal Absorption
  • Lipids / blood*
  • Lipids / pharmacokinetics
  • Mice, Knockout, ApoE
  • alpha-Cyclodextrins / metabolism
  • alpha-Cyclodextrins / pharmacology*
  • beta-Cyclodextrins / metabolism
  • beta-Cyclodextrins / pharmacology

Substances

  • Lipids
  • alpha-Cyclodextrins
  • beta-Cyclodextrins
  • betadex
  • alpha-cyclodextrin