The microbiome diversifies long-to short-chain fatty acid-derived N-acyl lipids
: Mannochio-Russo, Helena; Charron-Lamoureux, Vincent; van Faassen, Martijn; Lamichhane, Santosh; Nunes, Wilhan D. Goncalves; 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 Jr, 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.
Publisher: CELL PRESS
: CAMBRIDGE
: 2025
: Cell
: CELL
: CELL
: 188
: 15
: 4154
: 4169.e19
: 16
: 0092-8674
: 1097-4172
DOI: https://doi.org/10.1016/j.cell.2025.05.015
: https://doi.org/10.1016/j.cell.2025.05.015
: https://research.utu.fi/converis/portal/detail/Publication/499461279
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.
:
We thank the NIH (NIDDK) for supporting the development of tools for structure elucidation (R01DK136117) and the Collaborative Microbial Metabolite Center (U24DK133658), and the HIV Neurobehavioral Research Center (HNRC) is supported by center award P30MH062512 from NIMH. This work was further supported by BBSRC-NSF award 2152526. Research reported in this publication was supported in part by the National Center for Complementary and Integrative Health of the NIH under award number F32AT011475 to N.E.A. and by the Maternal and Pediatric Precision in Therapeutics project (P50HD106463). X.S. was supported by the National Key R&D Program of China (2022YFA0807300 and 2023YFA1800200), NSF of China (32270945), and STCSM (22ZR1468700 and 22140902400). S.L. was supported by Research Council of Finland funding (no. 363417). J.J.K. was supported by the NIH CTSA grant UL1TR001442 and the UCSD Microbiome Seed Grant. M.R. was supported by the NIH grant R37AI126277. G.T.W. was supported by the NIH training grant T32AI007036. G.J.N. was supported by the NIH fellowship F31AI186410. We also thank Dr. Jessica L. Metcalf for supervision of the human cadaver decomposition study and Dr. Robert Heaton for the participation in the development of the clinical cohort of HIV infection.
