Nature:全面分析菌群对宿主代谢组的影响,发现新型结合型胆汁酸
创作:mildbreeze 审核:mildbreeze 03月01日
  • 对比无菌和有菌小鼠29个器官的代谢组,发现菌群影响了所有器官(尤其是肠道)的化学特征,主要促进分解代谢;
  • 鉴定出小肠中的3种由菌群产生的氨基酸结合型胆酸(Phe-chol,Tyr-chol,Leu-chol),其中氨基酸通过酰胺键连接至胆盐主链,是菌群胆汁酸代谢的新机制;
  • 这些新型结合型胆汁酸也存在于人类中,在炎症性肠病和囊性纤维化患者中富集;
  • 这些胆汁酸可激活人细胞的FXR受体,给小鼠灌胃后可减少肝脏胆汁酸合成的FXR靶基因表达。
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mildbreeze
在宿主与微生物的共生系统中,菌群产生的大量生物活性分子,对宿主生理具有不可忽视的影响。Nature最新发表的一项研究,用质谱信息学和数据可视化方法,系统性分析了菌群对小鼠代谢组的影响,意外地发现了一类新型的氨基酸结合型胆汁酸,代表了菌群的第5种胆汁酸代谢机制。研究者通过使用Mass Spectrometry Search Tool分析了上千个公开的数据集,确认了这些胆汁酸也存在于人类中,并且在炎症性肠病和囊性纤维化患者中更常见。细胞和小鼠试验表明,这些胆汁酸可能通过作用于FXR通路影响宿主生理。该研究为用代谢组学方法研究菌群-宿主互作带来新启示。
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Nature [IF:43.07]

Global chemical effects of the microbiome include new bile-acid conjugations

微生物组的全局性化学效应包括新型胆汁酸结合物

10.1038/s41586-020-2047-9

02-26, Article

Abstract & Authors:展开

Abstract:收起
A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease1,2,3,4,5,6,7,8,9. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units10), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches11,12,13 to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry14. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis.

First Authors:
Robert A Quinn

Correspondence Authors:
Pieter C Dorrestein

All Authors:
Robert A Quinn,Alexey V Melnik,Alison Vrbanac,Ting Fu,Kathryn A Patras,Mitchell P Christy,Zsolt Bodai,Pedro Belda-Ferre,Anupriya Tripathi,Lawton K Chung,Michael Downes,Ryan D Welch,Melissa Quinn,Greg Humphrey,Morgan Panitchpakdi,Kelly C Weldon,Alexander Aksenov,Ricardo da Silva,Julian Avila-Pacheco,Clary Clish,Sena Bae,Himel Mallick,Eric A Franzosa,Jason Lloyd-Price,Robert Bussell,Taren Thron,Andrew T Nelson,Mingxun Wang,Eric Leszczynski,Fernando Vargas,Julia M Gauglitz,Michael J Meehan,Emily Gentry,Timothy D Arthur,Alexis C Komor,Orit Poulsen,Brigid S Boland,John T Chang,William J Sandborn,Meerana Lim,Neha Garg,Julie C Lumeng,Ramnik J Xavier,Barbara I Kazmierczak,Ruchi Jain,Marie Egan,Kyung E Rhee,David Ferguson,Manuela Raffatellu,Hera Vlamakis,Gabriel G Haddad,Dionicio Siegel,Curtis Huttenhower,Sarkis K Mazmanian,Ronald M Evans,Victor Nizet,Rob Knight,Pieter C Dorrestein

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ScienceDaily新闻网站

How resident microbes restructure body chemistry

2020-02-26

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Nature Chemical Biology期刊

A gut reaction

2020-03-20

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