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Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Author

Listed:
  • Sara Vieira-Silva

    (Rega Institute, KU Leuven
    Center for Microbiology, VIB)

  • Gwen Falony

    (Rega Institute, KU Leuven
    Center for Microbiology, VIB)

  • Eugeni Belda

    (INSERM, Sorbonne Université
    Integromics Unit)

  • Trine Nielsen

    (University of Copenhagen)

  • Judith Aron-Wisnewsky

    (INSERM, Sorbonne Université
    Pitie-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris)

  • Rima Chakaroun

    (University of Leipzig Medical Center)

  • Sofia K. Forslund

    (Charité-Universitätsmedizin and Max-Delbrück Center
    European Molecular Biology Laboratory
    Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC)
    Partner Site Berlin)

  • Karen Assmann

    (INSERM, Sorbonne Université)

  • Mireia Valles-Colomer

    (Rega Institute, KU Leuven
    Center for Microbiology, VIB)

  • Thi Thuy Duyen Nguyen

    (Rega Institute, KU Leuven
    Center for Microbiology, VIB)

  • Sebastian Proost

    (Rega Institute, KU Leuven
    Center for Microbiology, VIB)

  • Edi Prifti

    (INSERM, Sorbonne Université
    Integromics Unit
    Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, UMMISCO, Sorbonne Université, IRD)

  • Valentina Tremaroli

    (University of Gothenburg)

  • Nicolas Pons

    (Université Paris-Saclay, INRAE, Metagenopolis)

  • Emmanuelle Chatelier

    (Université Paris-Saclay, INRAE, Metagenopolis)

  • Fabrizio Andreelli

    (INSERM, Sorbonne Université
    Pitie-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris)

  • Jean-Phillippe Bastard

    (UF Biomarqueurs Inflammatoires et Métaboliques, Biochemistry and Hormonology Department, Tenon Hospital, Assistance Publique Hôpitaux de Paris
    Centre de Recherche Saint-Antoine, Sorbonne Université-INSERM UMR-S 938, IHU ICAN)

  • Luis Pedro Coelho

    (European Molecular Biology Laboratory
    Fudan University)

  • Nathalie Galleron

    (Université Paris-Saclay, INRAE, Metagenopolis)

  • Tue H. Hansen

    (University of Copenhagen)

  • Jean-Sébastien Hulot

    (NICO Cardio-oncology Program, CIC-1421, Department of Pharmacology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, INSERM, Sorbonne Université
    Université de Paris, PARCC, INSERM
    CIC1418 and DMU CARTE, Assistance Publique–Hôpitaux de Paris, Hôpital Européen Georges-Pompidou)

  • Christian Lewinter

    (Rigshospitalet, University of Copenhagen)

  • Helle K. Pedersen

    (University of Copenhagen)

  • Benoit Quinquis

    (Université Paris-Saclay, INRAE, Metagenopolis)

  • Christine Rouault

    (INSERM, Sorbonne Université)

  • Hugo Roume

    (Université Paris-Saclay, INRAE, Metagenopolis)

  • Joe-Elie Salem

    (NICO Cardio-oncology Program, CIC-1421, Department of Pharmacology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, INSERM, Sorbonne Université)

  • Nadja B. Søndertoft

    (University of Copenhagen)

  • Sothea Touch

    (INSERM, Sorbonne Université)

  • Marc-Emmanuel Dumas

    (Imperial College London
    Imperial College London)

  • Stanislav Dusko Ehrlich

    (Université Paris-Saclay, INRAE, Metagenopolis)

  • Pilar Galan

    (Sorbonne Paris Cité Epidemiology and Statistics Research Centre (CRESS), U1153 INSERM, U1125, INRA, CNAM, University of Paris, Nutritional Epidemiology Research Team (EREN))

  • Jens P. Gøtze

    (Rigshospitalet, University of Copenhagen)

  • Torben Hansen

    (University of Copenhagen)

  • Jens J. Holst

    (University of Copenhagen)

  • Lars Køber

    (Rigshospitalet, University of Copenhagen)

  • Ivica Letunic

    (Biobyte Solutions)

  • Jens Nielsen

    (Chalmers University of Technology)

  • Jean-Michel Oppert

    (Pitie-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris)

  • Michael Stumvoll

    (University of Leipzig Medical Center
    Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig)

  • Henrik Vestergaard

    (University of Copenhagen)

  • Jean-Daniel Zucker

    (INSERM, Sorbonne Université
    Integromics Unit
    Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, UMMISCO, Sorbonne Université, IRD)

  • Peer Bork

    (European Molecular Biology Laboratory
    University of Heidelberg and European Molecular Biology Laboratory
    Biocenter, University of Würzburg)

  • Oluf Pedersen

    (University of Copenhagen)

  • Fredrik Bäckhed

    (University of Copenhagen
    University of Gothenburg)

  • Karine Clément

    (INSERM, Sorbonne Université
    Pitie-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris)

  • Jeroen Raes

    (Rega Institute, KU Leuven
    Center for Microbiology, VIB)

Abstract

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

Suggested Citation

  • Sara Vieira-Silva & Gwen Falony & Eugeni Belda & Trine Nielsen & Judith Aron-Wisnewsky & Rima Chakaroun & Sofia K. Forslund & Karen Assmann & Mireia Valles-Colomer & Thi Thuy Duyen Nguyen & Sebastian , 2020. "Statin therapy is associated with lower prevalence of gut microbiota dysbiosis," Nature, Nature, vol. 581(7808), pages 310-315, May.
  • Handle: RePEc:nat:nature:v:581:y:2020:i:7808:d:10.1038_s41586-020-2269-x
    DOI: 10.1038/s41586-020-2269-x
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    Cited by:

    1. Yadid M. Algavi & Elhanan Borenstein, 2023. "A data-driven approach for predicting the impact of drugs on the human microbiome," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Doris Vandeputte & Lindsey Commer & Raul Y. Tito & Gunter Kathagen & João Sabino & Séverine Vermeire & Karoline Faust & Jeroen Raes, 2021. "Temporal variability in quantitative human gut microbiome profiles and implications for clinical research," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Julien Tap & Franck Lejzerowicz & Aurélie Cotillard & Matthieu Pichaud & Daniel McDonald & Se Jin Song & Rob Knight & Patrick Veiga & Muriel Derrien, 2023. "Global branches and local states of the human gut microbiome define associations with environmental and intrinsic factors," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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