TY - JOUR
T1 - Gut feelings about bacterial steroid-17,20-desmolase
AU - Ly, Lindsey K
AU - Doden, Heidi L
AU - Ridlon, Jason M
N1 - Funding Information:
We gratefully acknowledge Rafael C. Bernardi, Department of Physics at Auburn University, for support in rendering DesC and DesE crystal structure figures. This work was supported by grants from the National Institutes of Health (R01GM134423 and R03AI147127). The graphical abstract and Figs. 1, 2 and 4 were created using Biorender.com.
Funding Information:
We gratefully acknowledge Rafael C. Bernardi, Department of Physics at Auburn University, for support in rendering DesC and DesE crystal structure figures. This work was supported by grants from the National Institutes of Health ( R01GM134423 and R03AI147127 ). The graphical abstract and Figs. 1, 2 and 4 were created using Biorender.com .
Publisher Copyright:
© 2021 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4/5
Y1 - 2021/4/5
N2 - 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.
AB - 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.
KW - 11-Oxy-androgen
KW - Cortisol
KW - GALF
KW - Glucocorticoid
KW - Hydroxysteroid dehydrogenase
KW - Microbiome
KW - Steroid-17,20-desmolase
KW - Sterolbiome
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U2 - 10.1016/j.mce.2021.111174
DO - 10.1016/j.mce.2021.111174
M3 - Article
C2 - 33503463
SN - 0303-7207
VL - 525
SP - 111174
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 111174
ER -