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

• Published in: The FASEB journal Vol. 38; no. 20; pp. e70117 - n/a
• Main Authors: Hilman, Adrian, Sato, Tetsu, Wijatniko, Bambang Dwi, Fujimura, So, Nakamura, Katsushi, Miura, Hiroto, Iwatsuki, Ken, Inoue, Ryo, Suzuki, Takuya
• Format: Journal Article
• Language: English
• Published: United States 31.10.2024
• Subjects: Animals; bile acid; Bile Acids and Salts - metabolism; Colitis - chemically induced; Colitis - metabolism; Colitis - microbiology; Colon - metabolism; Colon - microbiology; Cyp2c55; Dextran Sulfate; Gastrointestinal Microbiome - physiology; Inflammation - metabolism; Inflammation - microbiology; intestinal inflammation; intestinal microbiota; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Male; Mice; Mice, Inbred C57BL; Pregnane X Receptor - genetics; Pregnane X Receptor - metabolism; intestinal microbiota; intestinal inflammation; Cyp2c55; bile acid
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.202401807R

Although the mutualistic relationship between the intestinal microbiota and the human host is crucial for maintaining health, the underlying mechanisms of this relationship remain unclear. In the present study, aiming to elucidate the regulatory mechanisms governing the Cyp2c55 expression, which is predominantly observed in colonic tissues, germ‐free, antibiotic‐administered and colitic mice, as well as mouse colonoids, were used as experimental models. RNA sequencing showed comparable decreases in the colonic Cyp2c55 expression in germ‐free and antibiotic‐administered mice, when compared with that in specific pathogen‐free mice. Furthermore, administration of dextran sulfate sodium decreased the Cyp2c55 expression in colitic mice. For these mice, a Pearson correlation analysis also showed a positive correlation between the Cyp2c55 expression and unconjugated bile acids (BAs), including chenodeoxycholic, muricholic, deoxycholic, lithocholic, and ursodeoxycholic acids, as well as taurine (T)‐conjugated secondary BAs, including deoxycholic acid. Moreover, bacterial genera, such as Muribaculaceae and unclassified Lachnospiraceae, also exhibited a positive correlation with these BAs. While administration of an agonist of the pregnane X receptor (PXR) increased the Cyp2c55 expression in mouse colonoids, inflammatory cytokines decreased it. In conclusion, Cyp2c55 was highly expressed in the colonic epithelial cells of mice in a microbiota‐dependent manner. The underlying mechanism seemed to involve a BA‐mediated PXR activation. In addition, the colonic expression of Cyp2c55 was regulated by the inflammatory response. Although the physiological function of Cyp2c55 remains largely unidentified, our findings suggested that Cyp2c55 may play a role in the mutualistic interaction between the intestinal microbiota and the intestinal homeostasis. Cyp2c55 is highly expressed in the colonic epithelial cells of mice in a microbiota‐dependent manner. The underlying mechanism seems to involve a BA‐mediated PXR activation. Furthermore, the colonic expression of Cyp2c55 is also subject to regulation by the inflammatory response. While the physiological function of Cyp2c55 remains largely unidentified, our findings suggested that Cyp2c55 may play a role in the mutualistic interaction between the intestinal microbiota and the intestinal homeostasis.