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

Chenhao Li; Martin Stražar; Ahmed M.T. Mohamed; Julian A. Pacheco; Rebecca L. Walker; Tina Lebar; Shijie Zhao; Julia Lockart; Andrea Dame; Kumar Thurimella; Sarah Jeanfavre; Eric M. Brown; Qi Yan Ang; Brittany Berdy; Dallis Sergio; Rachele Invernizzi; Antonio Tinoco; Gleb Pishchany; Ramachandran S. Vasan; Emily Balskus; Curtis Huttenhower; Hera Vlamakis; Clary Clish; Stanley Y. Shaw; Damian R. Plichta; Ramnik J. Xavier

doi:10.1016/j.cell.2024.03.014

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

Chenhao Li, Martin Stražar, Ahmed M.T. Mohamed, Julian A. Pacheco, Rebecca L. Walker, Tina Lebar, Shijie Zhao, Julia Lockart, Andrea Dame, Kumar Thurimella, Sarah Jeanfavre, Eric M. Brown, Qi Yan Ang, Brittany Berdy, Dallis Sergio, Rachele Invernizzi, Antonio Tinoco, Gleb Pishchany, Ramachandran S. Vasan, Emily BalskusCurtis Huttenhower, Hera Vlamakis, Clary Clish, Stanley Y. Shaw, Damian R. Plichta, Ramnik J. Xavier

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1834-1852.e19
Journal	Cell
Volume	187
Issue number	8
DOIs	https://doi.org/10.1016/j.cell.2024.03.014
State	Published - Apr 11 2024
Externally published	Yes

Keywords

Cardiovascular disease
Cholesterol
Metabolome
Microbiome
Oscillibacter

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2024.03.014

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Li, C., Stražar, M., Mohamed, A. M. T., Pacheco, J. A., Walker, R. L., Lebar, T., Zhao, S., Lockart, J., Dame, A., Thurimella, K., Jeanfavre, S., Brown, E. M., Ang, Q. Y., Berdy, B., Sergio, D., Invernizzi, R., Tinoco, A., Pishchany, G., Vasan, R. S., ... Xavier, R. J. (2024). Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria. Cell, 187(8), 1834-1852.e19. https://doi.org/10.1016/j.cell.2024.03.014

Li, C, Stražar, M, Mohamed, AMT, Pacheco, JA, Walker, RL, Lebar, T, Zhao, S, Lockart, J, Dame, A, Thurimella, K, Jeanfavre, S, Brown, EM, Ang, QY, Berdy, B, Sergio, D, Invernizzi, R, Tinoco, A, Pishchany, G, Vasan, RS, Balskus, E, Huttenhower, C, Vlamakis, H, Clish, C, Shaw, SY, Plichta, DR & Xavier, RJ 2024, 'Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria', Cell, vol. 187, no. 8, pp. 1834-1852.e19. https://doi.org/10.1016/j.cell.2024.03.014

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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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AU - Walker, Rebecca L.

AU - Lebar, Tina

AU - Zhao, Shijie

AU - Lockart, Julia

AU - Dame, Andrea

AU - Thurimella, Kumar

AU - Jeanfavre, Sarah

AU - Brown, Eric M.

AU - Ang, Qi Yan

AU - Berdy, Brittany

AU - Sergio, Dallis

AU - Invernizzi, Rachele

AU - Tinoco, Antonio

AU - Pishchany, Gleb

AU - Vasan, Ramachandran S.

AU - Balskus, Emily

AU - Huttenhower, Curtis

AU - Vlamakis, Hera

AU - Clish, Clary

AU - Shaw, Stanley Y.

AU - Plichta, Damian R.

AU - Xavier, Ramnik J.

PY - 2024/4/11

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N2 - 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.

AB - 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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KW - Cholesterol

KW - Metabolome

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

Abstract

Keywords

ASJC Scopus subject areas

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