TY - JOUR

T1 - Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

AU - Vieira-Silva, Sara

AU - Falony, Gwen

AU - Belda, Eugeni

AU - Nielsen, Trine

AU - Aron-Wisnewsky, Judith

AU - Chakaroun, Rima

AU - Forslund, Sofia K

AU - Assmann, Karen

AU - Valles-Colomer, Mireia

AU - Nguyen, Thi Thuy Duyen

AU - Proost, Sebastian

AU - Prifti, Edi

AU - Tremaroli, Valentina

AU - Pons, Nicolas

AU - Le Chatelier, Emmanuelle

AU - Andreelli, Fabrizio

AU - Bastard, Jean-Phillippe

AU - Coelho, Luis Pedro

AU - Galleron, Nathalie

AU - Hansen, Tue H

AU - Hulot, Jean-Sébastien

AU - Lewinter, Christian

AU - Pedersen, Helle K

AU - Quinquis, Benoit

AU - Rouault, Christine

AU - Roume, Hugo

AU - Salem, Joe-Elie

AU - Søndertoft, Nadja B

AU - Touch, Sothea

AU - Dumas, Marc-Emmanuel

AU - Ehrlich, Stanislav Dusko

AU - Galan, Pilar

AU - Gøtze, Jens P

AU - Hansen, Torben

AU - Holst, Jens J

AU - Køber, Lars

AU - Letunic, Ivica

AU - Nielsen, Jens

AU - Oppert, Jean-Michel

AU - Stumvoll, Michael

AU - Vestergaard, Henrik

AU - Zucker, Jean-Daniel

AU - Bork, Peer

AU - Pedersen, Oluf

AU - Bäckhed, Fredrik

AU - Clément, Karine

AU - Raes, Jeroen

AU - MetaCardis Consortium

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Bacteroides/isolation & purification

KW - Cohort Studies

KW - Cross-Sectional Studies

KW - Dysbiosis/epidemiology

KW - Faecalibacterium/isolation & purification

KW - Feces/microbiology

KW - Female

KW - Gastrointestinal Microbiome/drug effects

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage

KW - Inflammatory Bowel Diseases/microbiology

KW - Male

KW - Obesity/microbiology

KW - Prevalence

U2 - 10.1038/s41586-020-2269-x

DO - 10.1038/s41586-020-2269-x

M3 - Journal article

C2 - 32433607

VL - 581

SP - 310

EP - 315

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7808

ER -