Abstract 9700: Totum-070 Reduces Hypercholesterolemia in Western Diet Fed Mice and Increases Cholesterol Fecal Excretion

Lowering blood cholesterol level reduces the incidence of cardiovascular diseases. Totum-070 (T070) is a polyphenol-rich active substance composed by the association of 5 plant extracts. We tested the effect of supplementation of T070 in dyslipidemic mice and characterized the mechanisms of action. C57Bl/6 mice were fed with either a normal diet (ND) or a western diet (WD) for 6 weeks. Mice fed WD were split in different groups (vehicle, T070 1g/kg and T070 3g/kg) depending on the treatment received daily by gavage (n=14 per group). Compared to WD-fed mice, the concentration of total cholesterol was decreased after 3 weeks of supplementation by -9% (p<0.05) and -12.7% (p<0.01) with 1 g/kg T070 and 3 g/kg T070, respectively. At the end of the study, total cholesterol was reduced by -7.3% (n.s) and -11% (p<0.01) with 1 g/kg and 3 g/kg T070 compared to WD-fed mice. Mice receiving 1g/kg T070 exhibited similar body weight gain than mice from the WD group. On the contrary, WD-fed mice receiving 3 g/kg T070 had reduced body weight gain by 29.5% compared to WD-fed mice (p<0.01). The supplementation of T070 reduced hepatic steatosis in a dose-dependent manner with a 17.4% drop at 1 g/kg T070 (p<0.05) and a 40% reduction at 3g/kg T070 (p<0.0001) compared to WD-fed mice. Hepatic and intestinal gene expression were altered by WD feeding compared to ND, while supplementation with T070 tended to restore normal levels of expression on several genes implicated in lipid and lipoprotein metabolism. Fecal neutral sterols were quantified in feces collected at the end of the study. Sterol quantity was increased by 16% in feces from the 3g/kg T070 group compared to the WD group. Furthermore, a significant 13% increase in feces production was observed in mice supplemented with T070 3 g/kg compared to the mice fed with WD alone (p<0.01). Fresh feces were harvested of the mice and composition of microbiota was assessed by 16S rDNA sequencing. WD induced a decrease in richness (Chao) and diversity (Shannon) indexes, compared to ND. T070 supplementation was able to partially restore diversity index, compared to WD. In conclusion, T070 supplementation is a promising strategy to prevent hypercholesterolemia though increased of fecal cholesterol excretion and amelioration of gut microbial imbalance.