Supplementation with Natto and Red Yeast Rice Alters Gene Expressions in Cholesterol Metabolism Pathways in ApoE-/- Mice with Concurrent Changes in Gut Microbiota

We aimed to examine the effect of natto and red yeast rice (NR) supplementation on lipid and lipoprotein profiles, gene expressions of cholesterol metabolism, and the composition of gut microbiota in ApoE(-/-) mice. Forty-one male ApoE(-/-) mice aged 7-8 wks old were randomly fed a control diet (CD), CD + NR (oral gavage at 0.3 g/kg BW/day), high-fat and high-cholesterol diet (HFD), or HFD + NR for 12 wks. Fasting blood samples, liver and intestine tissues and fecal samples were collected at week 12. Biochemical parameters, gene expressions in cholesterol metabolism and gut microbiota composition and diversity were measured using standard methods. NR supplementation had no significant effect on lipid and lipoprotein profiles. Compared with the HFD group, HFD + NR resulted in higher mRNA expressions of HMGCR and CYP7A1 (both P-NR < 0.05) and ABCA1 (P-diet*NR = 0.0134, P-NR = 0.0407), lower mRNA expression of PCSK9 (P-diet*NR = 0.0002), lower fasting glucose concentrations (P-diet*NR = 0.0011), and lower relative abundance of genera Bacteroides and Lactococcus (both P-NR < 0.01) and Coriobacteriaceae_UCG-002 (P-diet*NR = 0.0007). The relative abundance of Lactococcus was inversely correlated with HMGCR and CYP7A1, and the relative abundance of Coriobacteriaceae_UCG-002 was positively correlated with PCSK9 and inversely correlated with ABCA1 (all P < 0.05). These findings suggest that NR supplementation may regulate gene expressions in cholesterol metabolism via changes in the gut microbiota in HFD-fed ApoE(-/-) mice.

Automated summary

This study investigated the effects of natto and red yeast rice (NR) supplementation on lipid and lipoprotein profiles, gene expressions of cholesterol metabolism, and gut microbiota composition in ApoE(-/-) mice. The results showed that NR supplementation had no significant impact on lipid and lipoprotein profiles, but HFD + NR group exhibited increased mRNA expressions of HMGCR, CYP7A1, and ABCA1, decreased mRNA expression of PCSK9, lowered fasting glucose concentrations, and decreased abundance of genera Bacteroides and Lactococcus as well as Coriobacteriaceae_UCG-002. These findings suggest that NR supplementation may affect cholesterol metabolism gene expressions through changes in gut microbiota.