Ripened Pu-Erh Tea Improved the Enterohepatic Circulation in a Circadian Rhythm Disorder Mice Model

Glucolipid metabolism, nitrogen metabolism, and inflammation are closely related to circadian rhythm disorder (CRD). Ripened Pu-erh tea (RPT) shows significant antidyslipidemic, antihyperurecemic, and anti-inflammatory effects. However, it is unclear whether healthy population are affected by CRD and whether long-term consumption of RPT can alleviate it. To investigate this problem, healthy mice were pretreated with RPT (0.25%, w/v) for 60 days and then subjected to CRD for 40 days. Our results indicated that healthy mice showed obesity, and the intestinal and liver inflammation increased after CRD, which were associated with the development of a metabolic disorder syndrome. RPT effectively reversed this trend by increasing the production and excretion rates of bile acid. RPT reshaped the disorder of gut microbiota caused by CRD and promoted the change of archaeal intestinal types from Firmicutes-dominant type to Bacteroidota-dominant type. In addition, by repairing the intestinal barrier function, RPT inhibited the infiltration of harmful microorganisms or metabolites through enterohepatic circulation, thus reducing the risk of chronic liver inflammation. In conclusion, RPT may reduce the risk of CRD-induced obesity in mice by increasing bile acid metabolism. The change of bile acid pool contributes to the reshaping of gut microflora, thus reducing intestinal inflammation and oxidative stress induced by CRD. Therefore, we speculated that the weakening of CRD damage caused by RPT is due to the improvement of bile acid-mediated enterohepatic circulation. It was found that 0.25% RPT (a human equivalent dose of 7 g/60 kg/day) has potential for regulating CRD.