Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria.

Autor:	Li C; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Stražar M; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Mohamed AMT; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Pacheco JA; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Walker RL; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Lebar T; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA., Zhao S; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Lockart J; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Dame A; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Thurimella K; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Jeanfavre S; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Brown EM; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Ang QY; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Berdy B; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Sergio D; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Invernizzi R; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Tinoco A; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA., Pishchany G; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Vasan RS; Boston University and NHLBI's Framingham Heart Study, Framingham, MA, USA; Sections of Preventive Medicine and Epidemiology and Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; University of Texas School of Public Health, San Antonio, TX, USA., Balskus E; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA., Huttenhower C; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard T.H. Chan School of Public Health, Boston, MA, USA., Vlamakis H; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Clish C; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Shaw SY; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Plichta DR; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Xavier RJ; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Apr 11; Vol. 187 (8), pp. 1834-1852.e19. Date of Electronic Publication: 2024 Apr 02.
DOI:	10.1016/j.cell.2024.03.014
Abstrakt:	Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health. Competing Interests: Declaration of interests R.J.X. is a member of the Scientific Advisory Boards at Nestlé and Magnet Biomedicine, a founder of Jnana and Celsius Therapeutics, and a board member of MoonLake Immunotherapeutics. A provisional patent application describing potential treatments for CVD using the isolates and related compositions described in this study has been filed. The authors listed on that application are R.J.X., C.L., M.S., A.M.T.M, and D.R.P. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu