Statin therapy is associated with lower prevalence of gut microbiota dysbiosis.

Autor: Vieira-Silva S; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.; Center for Microbiology, VIB, Leuven, Belgium., Falony G; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.; Center for Microbiology, VIB, Leuven, Belgium., Belda E; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France.; Institute of Cardiometabolism and Nutrition, Integromics Unit, Paris, France., Nielsen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Aron-Wisnewsky J; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France.; Nutrition Department, Pitie-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris, France., Chakaroun R; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany., Forslund SK; Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück Center, Berlin, Germany.; Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.; Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany., Assmann K; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France., Valles-Colomer M; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.; Center for Microbiology, VIB, Leuven, Belgium., Nguyen TTD; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.; Center for Microbiology, VIB, Leuven, Belgium., Proost S; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.; Center for Microbiology, VIB, Leuven, Belgium., Prifti E; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France.; Institute of Cardiometabolism and Nutrition, Integromics Unit, Paris, France.; Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, UMMISCO, Sorbonne Université, IRD, Bondy, France., Tremaroli V; Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Pons N; Université Paris-Saclay, INRAE, Metagenopolis, Jouy en Josas, France., Le Chatelier E; Université Paris-Saclay, INRAE, Metagenopolis, Jouy en Josas, France., Andreelli F; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France.; Diabetes Department, Pitie-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris, France., Bastard JP; UF Biomarqueurs Inflammatoires et Métaboliques, Biochemistry and Hormonology Department, Tenon Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.; Centre de Recherche Saint-Antoine, Sorbonne Université-INSERM UMR-S 938, IHU ICAN, Paris, France., Coelho LP; Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China., Galleron N; Université Paris-Saclay, INRAE, Metagenopolis, Jouy en Josas, France., Hansen TH; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hulot JS; NICO Cardio-oncology Program, CIC-1421, Department of Pharmacology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, INSERM, Sorbonne Université, Paris, France.; Université de Paris, PARCC, INSERM, Paris, France.; CIC1418 and DMU CARTE, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Paris, France., Lewinter C; Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Pedersen HK; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Quinquis B; Université Paris-Saclay, INRAE, Metagenopolis, Jouy en Josas, France., Rouault C; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France., Roume H; Université Paris-Saclay, INRAE, Metagenopolis, Jouy en Josas, France., Salem JE; NICO Cardio-oncology Program, CIC-1421, Department of Pharmacology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, INSERM, Sorbonne Université, Paris, France., Søndertoft NB; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Touch S; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France., Dumas ME; Computational and Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.; Genomic and Environmental Medicine, National Heart & Lung Institute, Faculty of Medicine, Imperial College London, London, UK., Ehrlich SD; Université Paris-Saclay, INRAE, Metagenopolis, Jouy en Josas, France., Galan P; Sorbonne Paris Cité Epidemiology and Statistics Research Centre (CRESS), U1153 INSERM, U1125, INRA, CNAM, University of Paris, Nutritional Epidemiology Research Team (EREN), Bobigny, France., Gøtze JP; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Holst JJ; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Køber L; Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Letunic I; Biobyte Solutions, Heidelberg, Germany., Nielsen J; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden., Oppert JM; Nutrition Department, Pitie-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris, France., Stumvoll M; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Leipzig, Germany., Vestergaard H; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Zucker JD; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France.; Institute of Cardiometabolism and Nutrition, Integromics Unit, Paris, France.; Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, UMMISCO, Sorbonne Université, IRD, Bondy, France., Bork P; Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany.; Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany., Pedersen O; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Bäckhed F; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Clément K; Nutrition and Obesities: Systemic Approaches Research Unit (NutriOmics), INSERM, Sorbonne Université, Paris, France. karine.clement@inserm.fr.; Nutrition Department, Pitie-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. karine.clement@inserm.fr., Raes J; Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium. jeroen.raes@kuleuven.be.; Center for Microbiology, VIB, Leuven, Belgium. jeroen.raes@kuleuven.be.
Jazyk: angličtina
Zdroj: Nature [Nature] 2020 May; Vol. 581 (7808), pp. 310-315. Date of Electronic Publication: 2020 May 06.
DOI: 10.1038/s41586-020-2269-x
Abstrakt: 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 humans 1,2 . Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities 1,2 , and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease 2 . Reported changes in stool consistency 3 and inflammation status 4 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.
Databáze: MEDLINE
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