dc.contributor.author
Zimmermann, Friederike
dc.contributor.author
Roessler, Johann
dc.contributor.author
Schmidt, David
dc.contributor.author
Jasina, Andrzej
dc.contributor.author
Schumann, Paul
dc.contributor.author
Gast, Martina
dc.contributor.author
Poller, Wolfgang
dc.contributor.author
Leistner, David
dc.contributor.author
Giral, Hector
dc.contributor.author
Kränkel, Nicolle
dc.contributor.author
Kratzer, Adelheid
dc.contributor.author
Schuchardt, Sven
dc.contributor.author
Heimesaat, Markus M.
dc.contributor.author
Landmesser, Ulf
dc.contributor.author
Haghikia, Arash
dc.date.accessioned
2020-07-09T07:30:37Z
dc.date.available
2020-07-09T07:30:37Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/27425
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-27181
dc.description.abstract
Background and aims:
The mechanisms of interindividual variation of lipid regulation by statins, such as the low-density lipoprotein cholesterol (LDL) lowering effects, are not fully understood yet. Here, we used a gut microbiota depleted mouse model to investigate the relation between the gut microbiota and the regulatory property of atorvastatin on blood lipids.
Methods:
Mice (C57BL/6) with intact gut microbiota or antibiotic induced abiotic mice (ABS) were put on standard chow diet (SCD) or high fat diet (HFD) for six weeks. Atorvastatin (10 mg/kg body weight/day) or a control vehicle were applied per gavage for the last four weeks of dietary treatment. Blood lipids including total cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and sphingolipids were measured to probe microbiota-dependent effects of atorvastatin. The expression of genes involved in hepatic and intestinal cholesterol metabolism was analyzed with qRT-PCR. The alteration of the microbiota profile was examined using 16S rRNA qPCR in mice with intact gut microbiota.
Results:
HFD feeding significantly increased total blood cholesterol and LDL levels, as compared to SCD in both mice with intact and depleted gut microbiota. The cholesterol lowering effect of atorvastatin was significantly attenuated in mice with depleted gut microbiota. Moreover, we observed a global shift in the abundance of several sphingolipids upon atorvastatin treatment which was absent in gut microbiota depleted mice. The regulatory effect of atorvastatin on the expression of distinct hepatic and intestinal cholesterol-regulating genes, including Ldlr, Srebp2 and Npc1l1 was altered upon depletion of gut microbiota. In response to HFD feeding, the relative abundance of the bacterial phyla Bacteroidetes decreased, while the abundance of Firmicutes increased. The altered ratio between Firmicutes to Bacteroidetes was partly reversed in HFD fed mice treated with atorvastatin.
Conclusions:
Our findings support a regulatory impact of atorvastatin on the gut microbial profile and, in turn, demonstrate a crucial role of the gut microbiome for atorvastatin-related effects on blood lipids. These results provide novel insights into potential microbiota-dependent mechanisms of lipid regulation by statins, which may account for variable response to statin treatment.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
gut microbiome
en
dc.subject
atorvastatin
en
dc.subject
cholesterol metabolism
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Impact of the Gut Microbiota on Atorvastatin Mediated Effects on Blood Lipids
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1596
dcterms.bibliographicCitation.doi
10.3390/jcm9051596
dcterms.bibliographicCitation.journaltitle
Journal of Clinical Medicine
dcterms.bibliographicCitation.originalpublishername
MDPI AG
dcterms.bibliographicCitation.volume
9
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
32466086
dcterms.isPartOf.eissn
2077-0383