Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega.

Steroid hormones like bile acids and glucocorticoids are vital for signaling in vertebrates. Their activity is influenced by structural modifications. Host and microbial enzymes called hydroxysteroid dehydrogenases (HSDHs) can alter these structures. These enzymes can convert hydroxyl groups to keto groups and vice versa. This process affects the biological activity and physical properties of steroids. Some microbial HSDHs can epimerize steroids from α-hydroxy to β-hydroxy forms. Others can convert β-hydroxy to ω-hydroxy configurations, as seen with ω-muricholic acid. These transformations may change how steroids interact with host receptors. Despite progress, the full role of microbial HSDHs remains unclear.

This review aims to clarify how microbial HSDHs affect steroid metabolism. Specifically, it focuses on bile acids and glucocorticoids. The goal is to highlight the biotransformation processes performed by gut microbiota. These enzymes may influence disease mechanisms and receptor activation. Understanding these transformations could reveal new therapeutic strategies. The study also seeks to identify gaps in current knowledge about microbial HSDHs. By examining their role in steroid pool modulation, it may guide future research directions. This work provides a framework for exploring microbial contributions to steroid signaling.

The authors conducted a literature review focusing on microbial HSDHs and their effects on steroid hormones. They analyzed studies on bile acid and glucocorticoid metabolism. The review synthesized findings from multiple disciplines including microbiology and endocrinology. The approach emphasized biotransformation pathways involving hydroxyl and keto group conversions. The analysis included structural changes like α- to β-hydroxy epimerization. The study also considered ω-muricholic acid transformations. The authors evaluated how these changes affect steroid activity and toxicity. The review structure allowed for a comprehensive overview of current knowledge.

Microbial HSDHs can reversibly convert hydroxyl groups to keto groups in steroids. These enzymes can epimerize steroids from α-hydroxy to β-hydroxy configurations. Some HSDHs convert β-hydroxy to ω-hydroxy forms, as in ω-muricholic acid. These transformations alter the physicochemical properties of steroids. The resulting products may act as activators or inhibitors of host receptors. These changes can influence solubility in fecal water and modulate toxicity. Microbial HSDHs are linked to diseases like colorectal cancer and prostate cancer. These findings suggest potential therapeutic applications for microbial HSDHs.

The authors suggest microbial HSDHs may modulate steroid pools in the host. These enzymes could influence disease mechanisms by altering steroid activity. The review highlights the need for further study on microbial HSDHs. The authors propose these enzymes may serve as druggable targets in the future. The findings indicate microbial HSDHs can affect receptor interactions and toxicity. The study emphasizes the importance of understanding biotransformation pathways. The authors suggest these enzymes could be therapeutic tools for modulating steroid signaling. These conclusions are based on current literature and suggest future research directions.