「分子ロゼッタ・ストーン」が明かすマイクロバイオームとの対話(“Molecular Rosetta Stone” Reveals How our Microbiome Talks to Us)

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2024-03-11 カリフォルニア大学サンディエゴ校(UCSD)

カリフォルニア大学サンディエゴ校の研究者たちは、腸内細菌が体内で使う胆汁酸の数千もの新種を発見しました。これにより、腸内細菌の働きやそのメカニズムを理解するための語彙が大幅に広がりました。胆汁酸は肝臓で生成され、腸で消化を助ける役割を果たすだけでなく、免疫系や代謝機能を調節する重要な役割も担っています。これにより、腸内細菌が他の臓器に影響を与える仕組みが明らかになりました。

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過小評価されている胆汁酸修飾の多様性 The underappreciated diversity of bile acid modifications

Ipsita Mohanty,Helena Mannochio-Russo,Joshua V. Schweer,…,Mingxun Wang,Allegra T. Aron,Pieter C. Dorrestein,Show all authors
Cell  Published:March 11, 2024
DOI:https://doi.org/10.1016/j.cell.2024.02.019

Highlights

•Mining of public, untargeted LC-MS/MS data reveals a large diversity of bile acids

•This work created an MS/MS spectral library resource of modified bile acids

•Polyamine biosynthetic pathway-derived metabolites amidated to bile acids discovered

•American-to-Mediterranean diet transition altered levels of polyamine bile amidates

Summary

The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.

Graphical abstract

Figure thumbnail fx1

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