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Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria.
Li, Chenhao; Strazar, Martin; Mohamed, Ahmed M T; Pacheco, Julian A; Walker, Rebecca L; Lebar, Tina; Zhao, Shijie; Lockart, Julia; Dame, Andrea; Thurimella, Kumar; Jeanfavre, Sarah; Brown, Eric M; Ang, Qi Yan; Berdy, Brittany; Sergio, Dallis; Invernizzi, Rachele; Tinoco, Antonio; Pishchany, Gleb; Vasan, Ramachandran S; Balskus, Emily; Huttenhower, Curtis; Vlamakis, Hera; Clish, Clary; Shaw, Stanley Y; Plichta, Damian R; Xavier, Ramnik J.
Affiliation
  • 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.
  • Strazar 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.
Cell ; 187(8): 1834-1852.e19, 2024 Apr 11.
Article in En | MEDLINE | ID: mdl-38569543
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Health context: 3_ND Database: MEDLINE Main subject: Bacteria / Cardiovascular Diseases / Cholesterol / Gastrointestinal Microbiome Limits: Humans Language: En Journal: Cell Year: 2024 Document type: Article
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Full text: 1 Collection: 01-internacional Health context: 3_ND Database: MEDLINE Main subject: Bacteria / Cardiovascular Diseases / Cholesterol / Gastrointestinal Microbiome Limits: Humans Language: En Journal: Cell Year: 2024 Document type: Article