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Abstract
The gut microbiome contributes to the variation of blood lipid levels, and secondary bile acids are associated with the effect of statins. Yet, our knowledge of how statins, one of our most common drug groups, affect the human microbiome is scarce. We aimed to characterize the effect of rosuvastatin on gut microbiome composition and inferred genetic content in stool samples from a randomized controlled trial (n = 66). No taxa were significantly altered by rosuvastatin during the study. However, rosuvastatin-treated participants showed a reduction in the collective genetic potential to transport and metabolize precursors of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO, p < 0.01), and an increase of related metabolites betaine and γ-butyrobetaine in plasma (p < 0.01). Exploratory analyses in the rosuvastatin group showed that participants with the least favorable treatment response (defined as < median change in high-density/low-density lipoprotein (HDL/LDL) ratio) showed a marked increase in TMAO-levels compared to those with a more favorable response (p < 0.05). Our data suggest that while rosuvastatin has a limited effect on gut microbiome composition, it could exert broader collective effects on the microbiome relevant to their function, providing a rationale for further studies of the influence of statins on the gut microbiome.
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1 Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
2 Oslo University Hospital Rikshospitalet, Department of Cardiology, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
3 Oslo University Hospital, Rikshospitalet, Department of Radiology, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
4 Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
5 Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
6 Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
7 Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway (GRID:grid.10919.30) (ISNI:0000000122595234)
8 University of Bergen, Department of Clinical Science, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443)
9 University of Bergen, Department of Clinical Science, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443); Haukeland University Hospital, Department of Heart Disease, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393)
10 Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Ullevål, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
11 Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Oslo University Hospital Rikshospitalet, Department of Cardiology, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)
12 Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Section of Gastroenterology, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485)