Statin therapy is associated with lower prevalence of gut microbiota dysbiosis
Journal article, 2020
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.
Author
Sara Vieira-Silva
KU Leuven
Gwen Falony
KU Leuven
Eugeni Belda
Pierre and Marie Curie University (UPMC)
Trine Nielsen
University of Copenhagen
Judith Aron-Wisnewsky
Pierre and Marie Curie University (UPMC)
Rima Chakaroun
Leipzig University
Sofia K. Forslund
The Max Delbrück Center for Molecular Medicine
Karen Assmann
Pierre and Marie Curie University (UPMC)
Mireia Vallès-Colomer
KU Leuven
Thi Thuy Duyen Nguyen
KU Leuven
Sebastian Proost
KU Leuven
Edi Prifti
Pierre and Marie Curie University (UPMC)
Valentina Tremaroli
Wallenberg Lab.
Nicolas Pons
University Paris-Saclay
Emmanuelle Le Chatelier
University Paris-Saclay
Fabrizio Andreelli
Pierre and Marie Curie University (UPMC)
Jean-Phillippe Bastard
Assistance publique – Hôpitaux de Paris (AP-HP)
Luis P. Coelho
European Molecular Biology Laboratory
Nathalie Galleron
University Paris-Saclay
Tue H. Hansen
University of Copenhagen
Jean-Sébastien Hulot
Assistance publique – Hôpitaux de Paris (AP-HP)
Christian Lewinter
University of Copenhagen
Helle K. Pedersen
University of Copenhagen
Benoit Quinquis
University Paris-Saclay
Christine Rouault
Pierre and Marie Curie University (UPMC)
Hugo Roume
University Paris-Saclay
Joe-Elie Salem
Assistance publique – Hôpitaux de Paris (AP-HP)
Nadja B. Søndertoft
University of Copenhagen
Sothea Touch
Pierre and Marie Curie University (UPMC)
Renato Alves
European Molecular Biology Laboratory
Chloe Amouyal
Pierre and Marie Curie University (UPMC)
Ehm Astrid Andersson Galijatovic
University of Copenhagen
Olivier Barthelemy
Assistance publique – Hôpitaux de Paris (AP-HP)
Jean-Paul Batisse
Assistance publique – Hôpitaux de Paris (AP-HP)
Magalie Berland
University Paris-Saclay
Randa Bittar
Assistance publique – Hôpitaux de Paris (AP-HP)
Hervé Blottière
University Paris-Saclay
Frederic Bosquet
Assistance publique – Hôpitaux de Paris (AP-HP)
Rachid Boubrit
Assistance publique – Hôpitaux de Paris (AP-HP)
Olivier Bourron
Assistance publique – Hôpitaux de Paris (AP-HP)
Mickael Camus
University Paris-Saclay
Dominique Cassuto
Assistance publique – Hôpitaux de Paris (AP-HP)
Cecile Ciangura
Assistance publique – Hôpitaux de Paris (AP-HP)
Jean-Philippe Collet
Assistance publique – Hôpitaux de Paris (AP-HP)
Maria-Carlota Dao
Pierre and Marie Curie University (UPMC)
Jean Debedat
Pierre and Marie Curie University (UPMC)
Morad Djebbar
Assistance publique – Hôpitaux de Paris (AP-HP)
Angélique Doré
University Paris-Saclay
Line Engelbrechtsen
University of Copenhagen
Soraya Fellahi
Assistance publique – Hôpitaux de Paris (AP-HP)
Sebastien Fromentin
University Paris-Saclay
Philippe Giral
Assistance publique – Hôpitaux de Paris (AP-HP)
Marianne Graine
Integromics Unit
Agnes Hartemann
Assistance publique – Hôpitaux de Paris (AP-HP)
Bolette Hartmann
University of Copenhagen
Gerard Helft
Assistance publique – Hôpitaux de Paris (AP-HP)
Serge Hercberg
U1153 INSERM
Malene Hornbak
University of Copenhagen
Richard Isnard
Assistance publique – Hôpitaux de Paris (AP-HP)
Sophie Jaqueminet
Assistance publique – Hôpitaux de Paris (AP-HP)
Niklas Rye Jørgensen
University of Copenhagen
Hanna Julienne
University Paris-Saclay
Johanne Justesen
University of Copenhagen
Judith Kammer
Leipzig University
Mathieu Kerneis
Assistance publique – Hôpitaux de Paris (AP-HP)
Jean Khemis
Assistance publique – Hôpitaux de Paris (AP-HP)
Nikolaj Krarup
University of Copenhagen
Michael Kuhn
European Molecular Biology Laboratory
Aurélie Lampuré
Pierre and Marie Curie University (UPMC)
Véronique Lejard
University Paris-Saclay
Florence Levenez
University Paris-Saclay
Lea Lucas-Martini
Assistance publique – Hôpitaux de Paris (AP-HP)
Robin Massey
University Paris-Saclay
Nicolas Maziers
University Paris-Saclay
Jonathan Medina-Stamminger
Assistance publique – Hôpitaux de Paris (AP-HP)
Lucas Moitinho-Silva
European Molecular Biology Laboratory
Gilles Montalescot
Assistance publique – Hôpitaux de Paris (AP-HP)
Sandrine Moutel
Assistance publique – Hôpitaux de Paris (AP-HP)
Laetitia Pasero Le Pavin
University Paris-Saclay
Christine Poitou-Bernert
Pierre and Marie Curie University (UPMC)
Francoise Pousset
Assistance publique – Hôpitaux de Paris (AP-HP)
Laurence Pouzoulet
Assistance publique – Hôpitaux de Paris (AP-HP)
Sebastian Schmidt
European Molecular Biology Laboratory
Johanne Silvain
Assistance publique – Hôpitaux de Paris (AP-HP)
Mathilde Svendstrup
University of Copenhagen
Timothy Swartz
Pierre and Marie Curie University (UPMC)
Thierry Vanduyvenboden
University Paris-Saclay
Camille Vatier
Assistance publique – Hôpitaux de Paris (AP-HP)
Eric Verger
Pierre and Marie Curie University (UPMC)
Stefanie Walther
Leipzig University
Marc-Emmanuel Dumas
Imperial College London
Stanislav Dusko Ehrlich
University Paris-Saclay
Pilar Galan
U1153 INSERM
Jens P. Gøtze
University of Copenhagen
Torben Hansen
University of Copenhagen
Jens Juul Holst
University of Copenhagen
Lars Køber
University of Copenhagen
Ivica Letunic
Biobyte Solutions
Jens B Nielsen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Jean-Michel Oppert
Assistance publique – Hôpitaux de Paris (AP-HP)
M. Stumvoll
Leipzig University
H. Vestergaard
University of Copenhagen
Jean-Daniel Zucker
Pierre and Marie Curie University (UPMC)
Peer Bork
European Molecular Biology Laboratory
O. B. Pedersen
University of Copenhagen
Fredrik Bäckhed
University of Copenhagen
K. Clement
Pierre and Marie Curie University (UPMC)
Jeroen Raes
KU Leuven
Nature
0028-0836 (ISSN) 1476-4687 (eISSN)
Vol. 581 7808 310-315Subject Categories
Bioinformatics and Systems Biology
DOI
10.1038/s41586-020-2269-x
PubMed
32433607