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感染使宿主为微生物群增强的病原体抗性做好准备。

Infection trains the host for microbiota-enhanced resistance to pathogens.

机构信息

Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Postdoctoral Research Associate Training Program, National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Cell. 2021 Feb 4;184(3):615-627.e17. doi: 10.1016/j.cell.2020.12.011. Epub 2021 Jan 15.

Abstract

The microbiota shields the host against infections in a process known as colonization resistance. How infections themselves shape this fundamental process remains largely unknown. Here, we show that gut microbiota from previously infected hosts display enhanced resistance to infection. This long-term functional remodeling is associated with altered bile acid metabolism leading to the expansion of taxa that utilize the sulfonic acid taurine. Notably, supplying exogenous taurine alone is sufficient to induce this alteration in microbiota function and enhance resistance. Mechanistically, taurine potentiates the microbiota's production of sulfide, an inhibitor of cellular respiration, which is key to host invasion by numerous pathogens. As such, pharmaceutical sequestration of sulfide perturbs the microbiota's composition and promotes pathogen invasion. Together, this work reveals a process by which the host, triggered by infection, can deploy taurine as a nutrient to nourish and train the microbiota, promoting its resistance to subsequent infection.

摘要

肠道微生物群通过定植抵抗过程保护宿主免受感染。然而,感染本身如何塑造这一基本过程在很大程度上仍是未知的。在这里,我们表明,先前感染过的宿主的肠道微生物群显示出对感染的增强抵抗力。这种长期的功能重塑与胆汁酸代谢的改变有关,导致利用磺酸牛磺酸的分类群扩张。值得注意的是,单独提供外源性牛磺酸就足以诱导这种微生物群功能的改变并增强抵抗力。从机制上讲,牛磺酸增强了微生物群产生硫化物的能力,硫化物是细胞呼吸的抑制剂,这是许多病原体入侵宿主的关键。因此,药物对硫化物的螯合会扰乱微生物群的组成并促进病原体的入侵。总之,这项工作揭示了一种宿主被感染触发的过程,宿主可以将牛磺酸作为一种营养物质来滋养和训练微生物群,从而提高其对后续感染的抵抗力。

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本文引用的文献

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Defining trained immunity and its role in health and disease.定义训练免疫及其在健康和疾病中的作用。
Nat Rev Immunol. 2020 Jun;20(6):375-388. doi: 10.1038/s41577-020-0285-6. Epub 2020 Mar 4.
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Genome Biol. 2019 Nov 28;20(1):257. doi: 10.1186/s13059-019-1891-0.
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Metabolism the Difficile Way: The Key to the Success of the Pathogen .艰难梭菌的代谢方式:病原体成功的关键
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