Apple polyphenol extract modulates bile acid metabolism and gut microbiota by regulating the circadian rhythms in daytime-restricted high fat diet feeding C57BL/6 male mice

The homeostasis of circadian clock linked to bile acid (BA) metabolism and gut microbiota has profound benefits in maintaining the health status of the host. The aim of this study was to investigate the prevention and regulation of apple polyphenol extract (APE) on BA metabolism and gut microbiota by means of modulation of circadian rhythms in mice. Eighty male C57BL/6 mice were randomized into four groups: 24-hour ad libitum standard chow group (AC), ad libitum HFD group (AF), restricted 12 h daytime HFD feeding group (DF), and daytime HFD feeding with APE treatment group (DP). Five weeks later, the mice were sacrificed at 6 h intervals over a 24 h period. The results showed that APE decreased body weight and induced daily rhythms of Cry1 and Ror alpha in the suprachiasmatic nucleus (SCN) and Clock, Cry1 and Cry2 in the ileum in daytime HFD mice. APE significantly increased the expression of hepatic FXR at ZT0 and BSEP at ZT12 and inhibited the expression of ileac FXR at ZT12, reduced levels of fecal TBAs, secondary BAs, and unconjugated BAs at ZT0. Meanwhile, APE regulated the diversity and composition of the gut microbiota, and increased the abundance of probiotics. Therefore, our work revealed that APE as a clock-regulating natural compound could modulate BA metabolism and gut microbiota and protect against circadian disruption in a clock-dependent manner.