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Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Sara Vieira-Silva 1 Gwen Falony 1 Eugeni Belda 2 Trine Nielsen 3 Judith Aron-Wisnewsky 2, 4 Rima Chakaroun 5 Sofia Forslund 6, 7, 8, 9 Karen Assmann 2 Mireia Valles-Colomer 1, 10 Thi Thuy Duyen Nguyen 1 Sebastian Proost 1 Edi Prifti 2, 11, 12 Valentina Tremaroli 13 Nicolas Pons 14 Emmanuelle Le Chatelier 14 Fabrizio Andreelli 2, 15 Jean-Phillippe Bastard 16, 17 Luis Pedro Coelho 7, 18 Nathalie Galleron 14 Tue H. Hansen 3 Jean-Sébastien Hulot 4, 19, 20 Christian Lewinter 21 Helle Pedersen 3 Benoit Quinquis 14 Christine Rouault 2 Hugo Roume 14 Joe-Elie Salem 20 Nadja Søndertoft 3 Sothea Touch 2 Metacardis Consortium Marc-Emmanuel Dumas 22, 23 Stanislav Dusko Ehrlich 14 Pilar Galan 24 Jens Gøtze 21 Torben Hansen 3 Jens Holst 3 Lars Køber 21 Ivica Letunic 25 Jens Nielsen 26 Jean-Michel Oppert 27 Michael Stumvoll 5 Henrik Vestergaard 3 Jean-Daniel Zucker 2, 11, 12 Peer Bork 28, 29, 30 Oluf Pedersen 3 Fredrik Bäckhed 3, 31 Karine Clément 2, 27 Jeroen Raes 1, 10
24 CRESS - U1153 - Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle
Université Sorbonne Paris Nord, CRESS (U1153 / UMR_A_1125 / UMR_S_1153) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité
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.
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https://hal.inrae.fr/hal-02964351
Contributor : Emmanuelle Le Chatelier <>
Submitted on : Monday, October 12, 2020 - 1:18:25 PM
Last modification on : Thursday, June 3, 2021 - 3:23:56 AM

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Sara Vieira-Silva, Gwen Falony, Eugeni Belda, Trine Nielsen, Judith Aron-Wisnewsky, et al.. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature, Nature Publishing Group, 2020, 581 (7808), pp.310-315. ⟨10.1038/s41586-020-2269-x⟩. ⟨hal-02964351⟩

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