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胆汁酸作为艰难梭菌芽孢的萌发剂,是适应肠道的证据吗?

Bile acids as germinants for Clostridioides difficile spores, evidence of adaptation to the gut?

作者信息

Vinay Gianni, Seppen Jurgen, Setlow Peter, Brul Stanley

机构信息

Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.

Department of Molecular Biology and Biophysics, UConn Health, Farmington, CT 06030-3305, United States.

出版信息

FEMS Microbiol Rev. 2025 Jan 14;49. doi: 10.1093/femsre/fuaf005.

DOI:10.1093/femsre/fuaf005
PMID:39924167
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11878537/
Abstract

Bacterial spores formed upon metabolic stress have minimal metabolic activity and can remain dormant for years. Nevertheless, they can sense the environment and germinate quickly upon exposure to various germinants. Germinated spores can then outgrow into vegetative cells. Germination of spores of some anaerobes, especially Clostridioides difficile, is triggered by cholic acid and taurocholic acid. Elevated levels of these bile acids are thought to correlate with a perturbed gut microbiome, which cannot efficiently convert primary bile acids into secondary bile acids. That bile acids are germination-triggers suggests these bacteria have a life cycle taking place partially in the mammalian digestive tract where bile acids are plentiful; notably bile acids can be made by all vertebrates. Thus, spores survive in the environment until taken up by a host where they encounter an environment suitable for germination and then proliferate in the largely anaerobic large intestine; some ultimately sporulate there, regenerating environmentally resistant spores in the C. difficile life cycle. This review summarizes current literature on the effects of bile acids and their metabolites on spore germination in the gut and evidence that adaptation to bile acids as germinants is a consequence of a life cycle both inside and outside the digestive tract.

摘要

在代谢应激下形成的细菌孢子代谢活性极低,可保持休眠数年。然而,它们能够感知环境,并在接触各种萌发剂后迅速萌发。萌发后的孢子随后可生长为营养细胞。某些厌氧菌,特别是艰难梭菌的孢子萌发,是由胆酸和牛磺胆酸触发的。这些胆汁酸水平的升高被认为与肠道微生物群紊乱有关,肠道微生物群无法有效地将初级胆汁酸转化为次级胆汁酸。胆汁酸作为萌发触发因素表明,这些细菌的生命周期部分发生在胆汁酸丰富的哺乳动物消化道中;值得注意的是,所有脊椎动物都能产生胆汁酸。因此,孢子在环境中存活,直到被宿主摄取,在那里它们遇到适合萌发的环境,然后在基本厌氧的大肠中增殖;有些最终在那里形成孢子,在艰难梭菌的生命周期中重新产生对环境有抗性的孢子。本综述总结了当前关于胆汁酸及其代谢产物对肠道孢子萌发影响的文献,以及适应胆汁酸作为萌发剂是消化道内外生命周期结果的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/457b2d5470bb/fuaf005fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/52c445587e56/fuaf005fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/5b77b1fc5163/fuaf005fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/e401635d734d/fuaf005fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/bb32ff89263b/fuaf005fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/457b2d5470bb/fuaf005fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/52c445587e56/fuaf005fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/5b77b1fc5163/fuaf005fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/e401635d734d/fuaf005fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/bb32ff89263b/fuaf005fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90cd/11878537/457b2d5470bb/fuaf005fig5.jpg

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Bile acids as germinants for Clostridioides difficile spores, evidence of adaptation to the gut?胆汁酸作为艰难梭菌芽孢的萌发剂,是适应肠道的证据吗?
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本文引用的文献

1
The Impact of YabG Mutations on Clostridioides difficile Spore Germination and Processing of Spore Substrates.YabG 突变对艰难梭菌孢子萌发和孢子基质加工的影响。
Mol Microbiol. 2024 Oct;122(4):534-548. doi: 10.1111/mmi.15316. Epub 2024 Sep 11.
2
The small acid-soluble proteins of Clostridioides difficile regulate sporulation in a SpoIVB2-dependent manner.艰难梭菌的小酸性可溶性蛋白以 SpoIVB2 依赖的方式调节孢子形成。
PLoS Pathog. 2024 Aug 30;20(8):e1012507. doi: 10.1371/journal.ppat.1012507. eCollection 2024 Aug.
3
Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.
健康与疾病中的胆汁酸代谢及信号传导:分子机制与治疗靶点
Signal Transduct Target Ther. 2024 Apr 26;9(1):97. doi: 10.1038/s41392-024-01811-6.
4
A sporulation signature protease is required for assembly of the spore surface layers, germination and host colonization in Clostridioides difficile.一种孢子形成特征蛋白酶是艰难梭菌孢子表面层组装、发芽和宿主定植所必需的。
PLoS Pathog. 2023 Nov 13;19(11):e1011741. doi: 10.1371/journal.ppat.1011741. eCollection 2023 Nov.
5
Clostridioides difficile Infection in Children: Recent Updates on Epidemiology, Diagnosis, Therapy.儿童艰难梭菌感染:流行病学、诊断、治疗的最新进展。
Pediatrics. 2023 Sep 1;152(3). doi: 10.1542/peds.2023-062307.
6
Single-spore germination analyses reveal that calcium released during germination functions in a feedforward loop.单孢子萌发分析表明,萌发过程中释放的钙在正反馈回路中发挥作用。
mSphere. 2023 Aug 24;8(4):e0000523. doi: 10.1128/msphere.00005-23. Epub 2023 Jun 20.
7
Bacterial spore germination receptors are nutrient-gated ion channels.细菌孢子发芽受体是营养门控离子通道。
Science. 2023 Apr 28;380(6643):387-391. doi: 10.1126/science.adg9829. Epub 2023 Apr 27.
8
Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut.胆汁盐水解酶塑造了胆汁酸图谱,并限制了艰难梭菌在小鼠肠道中的生长。
Nat Microbiol. 2023 Apr;8(4):611-628. doi: 10.1038/s41564-023-01337-7. Epub 2023 Mar 13.
9
Coprophagy in moose: A first observation.驼鹿的食粪行为:首次观察
Ecol Evol. 2023 Jan 19;13(1):e9757. doi: 10.1002/ece3.9757. eCollection 2023 Jan.
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Spore-Forming () in Wastewater Treatment Plants in Western Australia.西澳大利亚州污水处理厂中的孢子形成()。
Microbiol Spectr. 2023 Feb 14;11(1):e0358222. doi: 10.1128/spectrum.03582-22. Epub 2022 Dec 8.