The expression of intestinal Cyp2c55 is regulated by the microbiota and inflammation

Although the mutualistic relationship between the intestinal microbiota and thehuman host is crucial for maintaining health, the underlying mechanisms of thisrelationship remain unclear. In the present study, aiming to elucidate the regu-latory mechanisms governing the Cyp2c55 expression, which is predominantlyobserved in colonic tissues, germ-free, antibiotic-administered and colitic mice,as well as mouse colonoids, were used as experimental models. RNA sequencingshowed comparable decreases in the colonic Cyp2c55 expression in germ-freeand antibiotic-administered mice, when compared with that in specific pathogen-free mice. Furthermore, administration of dextran sulfate sodium decreasedthe Cyp2c55 expression in colitic mice. For these mice, a Pearson correlationanalysis also showed a positive correlation between the Cyp2c55 expression andunconjugated bile acids (BAs), including chenodeoxycholic, muricholic, deoxy-cholic, lithocholic, and ursodeoxycholic acids, as well as taurine (T)-conjugatedsecondary BAs, including deoxycholic acid. Moreover, bacterial genera, such asMuribaculaceae and unclassified Lachnospiraceae, also exhibited a positive cor-relation with these BAs. While administration of an agonist of the pregnane Xreceptor (PXR) increased the Cyp2c55 expression in mouse colonoids, inflam-matory cytokines decreased it. In conclusion, Cyp2c55 was highly expressedin the colonic epithelial cells of mice in a microbiota-dependent manner.