Pectin Penta-Oligogalacturonide Suppresses Intestinal Bile Acids Absorption and Downregulates the FXR-FGF15 Axis in High-Cholesterol Fed Mice

Haw pectin penta-oligogalacturonide (HPPS), purified from the hydrolysates of haw pectin, has important role in decreasing hepatic cholesterol accumulation and promoting bile acids (BA) excretion in the feces of mice fed a high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on BA reabsorption in ileum and biosynthesis in liver of mice. Results showed that HPPS increased fecal BA output by approximately 110%, but decreased ileal BA and the total BA pool size by approximately 47 and 36%, respectively, compared to HCD. Studies of molecular mechanism revealed that HPPS significantly decreased the mRNA and protein levels of farnesoid X receptor (FXR) in the small intestine of mice and inactivated the fibroblast growth factor 15 (FXR-FGF15) axis, which increased the mRNA and protein levels of CYP7A1 by approximately 204 and 104%, respectively, compared to HCD. Interestingly, the mRNA and protein levels of apical sodium-dependent bile acid transporter (ASBT) in the small intestine were approximately 128 and 73% higher in HPPS-fed mice than those in HCD-fed mice, respectively. However, no significant difference was detected for ASBT expression between HCD group and BA sequestrant cholestyramine group. These findings indicate that HPPS can suppress intestinal BA reabsorption and promoting hepatic BA biosynthesis. We speculated that HPPS could be ASBT competitive inhibitor rather than BA sequestrant in inhibiting BA reabsorption in ileum and improving cholesterol metabolism.