Gut feelings about bacterial steroid-17,20-desmolase

Lindsey K Ly, Heidi L Doden, Jason M Ridlon

Research output: Contribution to journalArticlepeer-review

Abstract

Advances in technology are only beginning to reveal the complex interactions between hosts and their resident microbiota that have co-evolved over centuries. In this review, we present compelling evidence that implicates the host-associated microbiome in the generation of 11β-hydroxyandrostenedione, leading to the formation of potent 11-oxy-androgens. Microbial steroid-17,20-desmolase cleaves the side-chain of glucocorticoids (GC), including cortisol (and its derivatives of cortisone, 5α-dihydrocortisol, and also (allo)- 3α, 5α-tetrahydrocortisol, but not 3α-5β-tetrahydrocortisol) and drugs (prednisone and dexamethasone). In addition to side-chain cleavage, we discuss the gut microbiome's robust potential to transform a myriad of steroids, mirroring much of the host's metabolism. We also explore the overlooked role of intestinal steroidogenesis and efflux pumps as a potential route for GC transport into the gut. Lastly, we propose several health implications from microbial steroid-17,20-desmolase function, including aberrant mineralocorticoid, GC, and androgen receptor signaling in colonocytes, immune cells, and prostate cells, which may exacerbate disease states.

Original languageEnglish (US)
Article number111174
Pages (from-to)111174
JournalMolecular and Cellular Endocrinology
Volume525
Early online dateJan 24 2021
DOIs
StatePublished - Apr 5 2021

Keywords

  • 11-Oxy-androgen
  • Cortisol
  • GALF
  • Glucocorticoid
  • Hydroxysteroid dehydrogenase
  • Microbiome
  • Steroid-17,20-desmolase
  • Sterolbiome

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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