Lipids constitute biological membranes and play a variety of roles as energy 49Gut microbiotaNon-targetedLipidomicsMetagenome profiles in antibiotic-treated conditions16S rRNAanalysisCorrelation analysis (lipidome vs. microbiome)sources, signaling molecules and their precursors. It is important to un-derstand at the molecular level the structural diversity of these lipid molecules and how they are recognized and utilized in vivo. Since abnormal lipid metabo-lism is an underlying factor in many diseases and lipids contain many bioactive molecules, this may lead to the discovery of new seeds for drug discovery and medical applications, such as early diagnosis and treatment.We established a non-targeted lipidomics platform packaged in MS-DIAL4 that derived a catalog of over 8,000 unique structures of 117 lipid class catego-ries. We created a comprehensive database of lipid structures with their mass spectrum properties, such as retention time, collision cross-section, and mass fragmentation pattern to correctly characterize lipids. This database has been published as a “lipidome atlas”.Host-microbiota interactions create a unique metabolic milieu that modu-lates intestinal environments. By combining non-targeted mass spectrometry with feature-based molecular spectrum networking technology, we revealed that lipids with complex structures are produced by the gut microbiota. Cor-rectly capturing such molecular groups, which have been overlooked by con-ventional targeted analysis, will lead to an understanding of the significance of bacterial species that correlate with various diseases such as cancer, obesity, and allergy. The method developed in this study is a technology that enables us to observe such changes in the bacterial flora as changes in the lipidome environ-ment from a bird’s eye view and is expected to contribute to the identification of functional metabolites that mediate host-bacteria interactions.Figure: Global profiling of gut microbiota-as-sociated lipid metabolites in antibiotic-treated miceWe conducted non-targeted lipidomics followed by feature-based molecular MS/MS spectral networking to characterize gut bacteria-dependent lipid subclasses in antibiotic-treated mice. Based on the integrated analy-sis of 985 lipid profiles and 16S rRNA sequence data providing 2,494 operational taxonomic units, we could successfully predict the bacterial species responsible for the production of a series of microbiota-associated lipids.Recent Major PublicationsOkahashi N, Ueda M, Yasuda S, Tsugawa H, Arita M. Global profiling of gut microbiota-associated lipid me-tabolites in antibiotic-treated mice by LC-MS/MS-based analyses. STAR Protoc 2, 100492 (2021)Hirata T, Yamamoto K, Ikeda K, Arita M. Functional lipidomics of vascular endothelial cells in response to laminar shear stress. FASEB J 35, e21301 (2021)Tsugawa H, Ikeda K, Takahashi M, Satoh A, Mori Y, Uchino H, Okahashi N, Yamada Y, Tada I, Bonini P, Higashi Y, Okazaki Y, Zhou Z, Zhu Z, Koelmel J, Cajka T, Fiehn O, Saito K, Arita M, Arita M. A lipidome atlas in MS-DIAL 4. Nat Biotechnol 38, 1159-1163 (2020)Invited presentationsArita M. “Advanced lipidomics technology and its appli-cation in biology” 5th RIKEN IMS-Stanford ISCBRM Joint Symposium (Online) November 2021Arita M. “Omega-3 fatty acid metabolism that controls inflammation and tissue homeostasis” World Congress of OMEGA3 Science and Technology (WCOST) (Online) November 2021Arita M. “Advanced non-targeted lipidomics and its application to vascular biology” 19th International Symposium on Atherosclerosis (ISA2021) (Kyoto, Japan) October 2021Arita M. “Advanced non-targeted lipidomics and its ap-plication in biology” The 5th JCS Council Forum on Basic Cardiovascular Research (Online) September 2021Arita M. “Biology of LipoQuality: Advanced lipidomics technology and its application in biology” 9th Inter-national Singapore Lipid Symposium (iSLS9) (Online) March 2021Laboratory for MetabolomicsTeam Leader: Makoto Arita
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