微生物群落使长链至短链脂肪酸衍生的N-酰基脂质多样化。

The microbiome diversifies long- to short-chain fatty acid-derived N-acyl lipids.

作者信息

Mannochio-Russo Helena, Charron-Lamoureux Vincent, van Faassen Martijn, Lamichhane Santosh, Gonçalves Nunes Wilhan D, Deleray Victoria, Ayala Adriana V, Tanaka Yuichiro, Patan Abubaker, Vittali Kyle, Rajkumar Prajit, El Abiead Yasin, Zhao Haoqi Nina, Gomes Paulo Wender Portal, Mohanty Ipsita, Lee Carlynda, Sund Aidan, Sharma Meera, Liu Yuanhao, Pattynama David, Walker Gregory T, Norton Grant J, Khatib Lora, Andalibi Mohammadsobhan S, Wang Crystal X, Ellis Ronald J, Moore David J, Iudicello Jennifer E, Franklin Donald, Letendre Scott, Chin Loryn, Walker Corinn, Renwick Simone, Zemlin Jasmine, Meehan Michael J, Song Xinyang, Kasper Dennis, Burcham Zachary, Kim Jane J, Kadakia Sejal, Raffatellu Manuela, Bode Lars, Chu Hiutung, Zengler Karsten, Wang Mingxun, Siegel Dionicio, Knight Rob, Dorrestein Pieter C

机构信息

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.

出版信息

Cell. 2025 Jun 9. doi: 10.1016/j.cell.2025.05.015.

DOI:10.1016/j.cell.2025.05.015

PMID:40499541

Abstract

N-Acyl lipids are important mediators of several biological processes including immune function and stress response. To enhance the detection of N-acyl lipids with untargeted mass spectrometry-based metabolomics, we created a reference spectral library retrieving N-acyl lipid patterns from 2,700 public datasets, identifying 851 N-acyl lipids that were detected 356,542 times. 777 are not documented in lipid structural databases, with 18% of these derived from short-chain fatty acids and found in the digestive tract and other organs. Their levels varied with diet and microbial colonization and in people living with diabetes. We used the library to link microbial N-acyl lipids, including histamine and polyamine conjugates, to HIV status and cognitive impairment. This resource will enhance the annotation of these compounds in future studies to further the understanding of their roles in health and disease and to highlight the value of large-scale untargeted metabolomics data for metabolite discovery.

摘要

N-酰基脂质是包括免疫功能和应激反应在内的多种生物过程的重要介质。为了通过基于非靶向质谱的代谢组学增强对N-酰基脂质的检测，我们创建了一个参考光谱库，从2700个公共数据集中检索N-酰基脂质模式，鉴定出851种N-酰基脂质，这些脂质被检测到356542次。脂质结构数据库中未记录其中777种，其中18%来源于短链脂肪酸，存在于消化道和其他器官中。它们的水平随饮食、微生物定植以及糖尿病患者的情况而变化。我们使用该库将包括组胺和多胺缀合物在内的微生物N-酰基脂质与HIV状态和认知障碍联系起来。这一资源将在未来研究中加强对这些化合物的注释，以进一步了解它们在健康和疾病中的作用，并突出大规模非靶向代谢组学数据在代谢物发现中的价值。