• The colonic expression of the Cyp2c55 gene is strongly regulated by the intestinal microbiota and inflammatory conditions.
• Metabolites of bile acids induce Cyp2c55 expression via activation of the nuclear receptor PXR, as demonstrated in mouse colonoids.
• In an inflammatory bowel disease (IBD) mouse model, Cyp2c55 expression was significantly downregulated, suggesting a role in maintaining intestinal homeostasis.

The intestinal microbiota plays a vital role in digestion, immunity, metabolism, and overall host health through a mutualistic relationship. However, the molecular mechanisms underlying this complex interaction remain incompletely understood. In this study, we focused on identifying genes whose expression is regulated by the intestinal microbiota, with particular attention to Cyp2c55, which is highly expressed in the mouse colon.

Transcriptomic analysis revealed that Cyp2c55 expression was markedly reduced in both germ-free and antibiotic-treated mice, indicating strong dependence on the presence of intestinal bacteria. Additionally, inflammatory conditions induced by dextran sulfate sodium (DSS) also suppressed Cyp2c55 expression, suggesting that both the microbiota and inflammation modulate its regulation.

Analysis of bile acid (BA) profiles showed a positive correlation between Cyp2c55 expression and levels of deconjugated and secondary bile acids. Experiments using mouse colonoids demonstrated that Cyp2c55 expression is upregulated by a PXR agonist and downregulated by inflammatory cytokines.

This study provides novel insights into the gene regulatory mechanisms influenced by the microbiota via bile acid signaling and highlights the potential role of Cyp2c55 in maintaining intestinal homeostasis. These findings may contribute to the development of new strategies for the prevention and treatment of intestinal disorders. Future research will focus on elucidating the precise physiological functions of Cyp2c55 and its relevance to human health.

• Journal: The FASEB Journal
• Title: The expression of intestinal Cyp2c55 is regulated by the microbiota and inflammation
• Authors: JAdrian Hilman, Tetsu Sato, Bambang Dwi Wijatniko, So Fujimura, Katsushi Nakamura, Hiroto Miura, Ken Iwatsuki, Ryo Inoue, Takuya Suzuki
• DOI: 10.1096/fj.202401807R.