Modulatory effect of Cyclocarya paliurus flavonoids on the intestinal microbiota and liver clock genes of circadian rhythm disorder mice model

Abstract Host circadian rhythm and gut microbiota have a bidirectional relationship, indicating that prebiotics or prebiotic-like substance is a possible way to regulate circadian rhythm. The modulatory effect of Cyclocarya paliurus flavonoids (CPF) on the intestinal microbiota and liver clock genes of a circadian rhythm disorder mouse model was investigated in the present study. 16S rDNA sequencing analysis showed that CPF ameliorated the imbalanced intestinal microbial structure induced by circadian rhythm disorder. Compared with the constant darkness (CD) group, the ratio of the relative abundance of Firmicutes to Bacteroidetes was significantly decreased after the intervention of CPF for 4 weeks. In addition, CPF significantly alleviated the disrupted diurnal oscillation and phase shift of the specific intestinal microbes and liver clock genes induced by constant darkness. Moreover, metagenomics analysis of gut microbiota showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched the most differentially expressed genes (DEGs) after CPF administration includes xenobiotics biodegradation and metabolism, carbohydrate metabolism and cell motility. The results suggested that CPF may positively regulate the gut flora disturbed by host circadian rhythm disorder, including its composition, diurnal oscillation and function, as well as affect the expression of liver clock genes, thus improving the host micro-ecology and health.