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
(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, 4)
,
Jean-Phillippe Bastard
(15, 16)
,
Luis Pedro Coelho
(7, 17)
,
Nathalie Galleron
(14)
,
Tue H. Hansen
(3)
,
Jean-Sébastien Hulot
(4, 18, 19)
,
Christian Lewinter
(20)
,
Helle Pedersen
(3)
,
Benoit Quinquis
(14)
,
Christine Rouault
(2)
,
Hugo Roume
(14)
,
Joe-Elie Salem
(19)
,
Nadja Søndertoft
(3)
,
Sothea Touch
(2)
,
Metacardis Consortium
,
Marc-Emmanuel Dumas
(21, 22)
,
Stanislav Dusko Ehrlich
(14)
,
Pilar Galan
(23)
,
Jens Gøtze
(20)
,
Torben Hansen
(3)
,
Jens Holst
(3)
,
Lars Køber
(20)
,
Ivica Letunic
(24)
,
Jens Nielsen
(25)
,
Jean-Michel Oppert
(4)
,
Michael Stumvoll
(5)
,
Henrik Vestergaard
(3)
,
Jean-Daniel Zucker
(2, 11, 12)
,
Peer Bork
(26, 27, 28)
,
Oluf Pedersen
(3)
,
Fredrik Bäckhed
(3, 29)
,
Karine Clément
(2, 4)
,
Jeroen Raes
(10)
1
Rega Institute for Medical Research [Leuven]
2 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
3 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
4 CHU Pitié-Salpêtrière [AP-HP]
5 University Hospital Leipzig = Universitätsklinikum Leipzig
6 Charité - UniversitätsMedizin = Berlin University Medicine
7 EMBL - European Molecular Biology Laboratory [Heidelberg]
8 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
9 DZHK - German Center for Cardiovascular Research
10 VIB-KU Leuven Center for Microbiology [Leuven, Belgium]
11 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
12 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
13 GU - Göteborgs Universitet = University of Gothenburg
14 MGP (US 1367) - MetaGenoPolis
15 CHU Tenon [AP-HP]
16 CRSA - Centre de Recherche Saint-Antoine
17 Fudan University [Shanghai]
18 CIC 1418 - CIC - HEGP
19 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
20 Rigshospitalet [Copenhagen]
21 NHLI - National Heart and Lung Institute [London]
22 Imperial College London
23 EREN [CRESS - U1153 / UMR_A 1125] - Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle
24 Biobyte Solution
25 Chalmers University of Technology [Göteborg]
26 EMBL - European Molecular Biology Laboratory
27 University of Heidelberg, Medical Faculty
28 JMU - Julius-Maximilians-Universität Würzburg = University of Würzburg
29 Sahlgrenska Academy at University of Gothenburg [Göteborg]
2 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
3 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
4 CHU Pitié-Salpêtrière [AP-HP]
5 University Hospital Leipzig = Universitätsklinikum Leipzig
6 Charité - UniversitätsMedizin = Berlin University Medicine
7 EMBL - European Molecular Biology Laboratory [Heidelberg]
8 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
9 DZHK - German Center for Cardiovascular Research
10 VIB-KU Leuven Center for Microbiology [Leuven, Belgium]
11 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
12 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
13 GU - Göteborgs Universitet = University of Gothenburg
14 MGP (US 1367) - MetaGenoPolis
15 CHU Tenon [AP-HP]
16 CRSA - Centre de Recherche Saint-Antoine
17 Fudan University [Shanghai]
18 CIC 1418 - CIC - HEGP
19 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
20 Rigshospitalet [Copenhagen]
21 NHLI - National Heart and Lung Institute [London]
22 Imperial College London
23 EREN [CRESS - U1153 / UMR_A 1125] - Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle
24 Biobyte Solution
25 Chalmers University of Technology [Göteborg]
26 EMBL - European Molecular Biology Laboratory
27 University of Heidelberg, Medical Faculty
28 JMU - Julius-Maximilians-Universität Würzburg = University of Würzburg
29 Sahlgrenska Academy at University of Gothenburg [Göteborg]
Sara Vieira-Silva
- Fonction : co premier-auteur
- PersonId : 775753
- ORCID : 0000-0002-4616-7602
Trine Nielsen
- Fonction : Auteur
- PersonId : 770024
- ORCID : 0000-0002-2066-7895
Sebastian Proost
- Fonction : Auteur
- PersonId : 784270
- ORCID : 0000-0002-6792-9442
Edi Prifti
- Fonction : Auteur
- PersonId : 1151183
- IdHAL : edi-prifti
- ORCID : 0000-0001-8861-1305
- IdRef : 155572822
Emmanuelle Le Chatelier
- Fonction : Auteur
- PersonId : 737756
- IdHAL : emmanuelle-le-chatelier
- ORCID : 0000-0002-2724-0536
Jean-Sébastien Hulot
- Fonction : Auteur
- PersonId : 759557
- ORCID : 0000-0001-5463-6117
- IdRef : 058500391
Joe-Elie Salem
- Fonction : Auteur
- PersonId : 777251
- IdHAL : joe-elie-salem
- ORCID : 0000-0002-0331-3307
- IdRef : 160947227
Nadja Søndertoft
- Fonction : Auteur
- PersonId : 802925
- ORCID : 0000-0001-6350-8117
Sothea Touch
- Fonction : Auteur
- PersonId : 783728
- ORCID : 0000-0002-1271-9704
Metacardis Consortium
- Fonction : Auteur
Marc-Emmanuel Dumas
- Fonction : Auteur
- PersonId : 750569
- IdHAL : marc-emmanuel-dumas
- ORCID : 0000-0001-9523-7024
Stanislav Dusko Ehrlich
- Fonction : Auteur
- PersonId : 1068832
- ORCID : 0000-0002-7563-4046
Pilar Galan
- Fonction : Auteur
- PersonId : 998753
Torben Hansen
- Fonction : Auteur
- PersonId : 758676
- ORCID : 0000-0001-8748-3831
Lars Køber
- Fonction : Auteur
- PersonId : 783646
- ORCID : 0000-0002-6635-1466
Jens Nielsen
- Fonction : Auteur
- PersonId : 758788
- ORCID : 0000-0002-9955-6003
Jean-Michel Oppert
- Fonction : Auteur
- PersonId : 763562
- ORCID : 0000-0003-0324-4820
- IdRef : 071407146
Henrik Vestergaard
- Fonction : Auteur
- PersonId : 782555
- ORCID : 0000-0003-3090-269X
Jean-Daniel Zucker
- Fonction : Auteur
- PersonId : 9387
- IdHAL : jean-daniel-zucker
- ORCID : 0000-0002-5597-7922
- IdRef : 070019495
Oluf Pedersen
- Fonction : Auteur
- PersonId : 802926
- ORCID : 0000-0002-3321-3972
Karine Clément
- Fonction : co dernier-auteur
- PersonId : 756892
- ORCID : 0000-0002-2489-3355
- IdRef : 07341512X
Résumé
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.
Domaines
Sciences du Vivant [q-bio]| Origine | Fichiers produits par l'(les) auteur(s) |
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