Diets Enriched in Sugar, Refined, or Whole Grain Differentially Influence Plasma Cholesterol Concentrations and Cholesterol Metabolism Pathways with Concurrent Changes in Bile Acid Profile and Gut Microbiota Composition in ApoE-/- Mice

This study aimed to compare the effects of diets enrichedin sugar,refined grain (RG), or whole grain (WG) on circulating cholesterolconcentrations and established and emerging mechanisms regulatingcholesterol metabolism. Forty-four male ApoE(-/-) mice aged8 weeks were randomly fed an isocaloric sugar-, RG-, or WG-enricheddiet for 12 weeks. Compared to WG-enriched diet, fasting plasma LDL-Cand HDL-C concentrations were higher and the mRNA expression of intestinalLXR-alpha was lower in sugar- and RG-enriched diets; plasma TC,non-HDL-C, TG and VLDL-C concentrations, and cecal concentrationsof lithocholic acid were higher and the mRNA expression of intestinalABCG5 was lower in sugar-enriched diet, and the mRNA expression ofhepatic IDOL and cecal concentrations of lithocholic and deoxycholicacids was higher in RG-enriched diet. The relative abundance of Akkermansia, Clostridia_UCG-014, Alistipes, and Alloprevotella, which werelower in sugar- and/or RG- than in WG-enriched diet, had inverse correlationswith fasting plasma cholesterol concentrations or cecal concentrationsof secondary bile acids and positive correlations with gene expressionsin intestinal cholesterol efflux. Conversely, the relative abundanceof Lactobacillus, Lachnoclostridium, Lachnospiraceae_NK4A136_group, Colidextribacter, and Helicobacter had reverse correlations. Bothsugar- and RG-enriched diets had unfavorable effects on cholesterolconcentrations; yet, their effects on the gene expressions of cholesterolefflux, uptake, bile acid synthesis, and bile acid concentrationswere distinctive and could be partially attributable to the concurrentchanges in gut microbiota.

Automated summary

This study compared the effects of diets enriched in sugar, refined grain (RG), or whole grain (WG) on cholesterol concentrations and related mechanisms. The results showed that sugar and RG diets increased plasma LDL-C and HDL-C concentrations, and decreased intestinal LXR-alpha gene expression compared to WG diet. Sugar diet increased plasma TC, non-HDL-C, TG, VLDL-C concentrations, and cecal lithocholic acid concentrations, and decreased intestinal ABCG5 gene expression; RG diet increased hepatic IDOL gene expression and cecal lithocholic and deoxycholic acid concentrations. The changes in gut microbiota were associated with cholesterol metabolism and bile acid concentrations.