Gut feelings about bacterial steroid-17,20-desmolase.

Gut feelings about bacterial steroid-17,20-desmolase.
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DOI:
10.1016/j.mce.2021.111174
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发表时间:
2021-04-05
影响因子:
4.1
通讯作者:
Ridlon JM
Ridlon JM
中科院分区:
医学2区
文献类型:
--
作者:
Ly LK;Doden HL;Ridlon JM

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技术的进步才刚刚开始揭示宿主与其常驻微生物群之间的复杂相互作用,这些微生物群已经共同进化了几个世纪。在这篇综述中,我们提出了令人信服的证据,表明宿主相关的微生物组参与了11β-羟基雄烯二酮的产生,导致了有效的11-氧雄激素的形成。微生物类固醇-17,20-碳链裂解酶(英语:Microbial steroid-17,20-desmolase)裂解糖皮质激素(GC)的侧链,包括皮质醇(及其衍生物可的松、5α-二氢皮质醇和(别洛)-3 α,5α-四氢皮质醇),但不包括3α−5β-四氢皮质醇)和药物(泼尼松和地塞米松)。除了侧链裂解,我们还讨论了肠道微生物组转化无数类固醇的强大潜力,反映了宿主的大部分代谢。我们还探讨了被忽视的作用,肠道类固醇生成和外排泵作为一个潜在的途径GC运输到肠道。最后,我们提出了微生物类固醇-17,20-碳链酶功能的几个健康影响,包括异常盐皮质激素,GC和雄激素受体信号在结肠细胞,免疫细胞和前列腺细胞,这可能会加剧疾病状态。
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.
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