Gut Microbiome Associates With Lipid-Lowering Effect of Rosuvastatin in Vivo

Abstract

Background: Statin has been widely used to treat hyperlipidemia because of its high potency in decreasing cholesterol levels. The present study aimed to examine the lipid-lowering effect of rosuvastatin and the composition, diversity and species abundance of gut microbiome in association with rosuvastatin efficacy. Trial registration: ChiCTR-ORC-17013212 at the First Affiliated Hospital of Dalian Medical University, November 2, 2017.Results: Totally 64 patients with hyperlipidemia were treated with 10 mg/day of rosuvastatin for 4–8 weeks. Blood lipid indicators triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL-C) were measured before and after the treatment. Stool samples were collected right after the treatment. Following total DNA extraction and PCR amplification of 16S rRNA gene, Illumina sequencing was performed for gut microbiome identification, classification and characterization. All the patients showed a significant blood lipid reduction after the treatment. The patients were grouped according to parallel manner design. Group I had 33 patients whose blood lipid levels dropped to the normal levels from week 4, with 58.5% reduction in LDL-C and 26.6% reduction in TC. Group II had 31 patients whose blood lipid levels were still above the normal levels after 8 weeks therapy, but with 41.9% reduction in LDL-C and 31.2% reduction in TC. Based on Operational Taxonomic Unit data, Alpha-diversity by Shannon Index was different between the two groups, and beta-diversity by Principle Component Analysis exhibited separated patterns of the two groups. The differences were also observed in the relative-abundance at phylum, family, and genus levels of the two groups. Linear discriminate analysis illustrated that the abundance of 29 taxa was higher in group I, while the abundance of other 13 taxa was higher in group II. Phyla Firmicutes and Fusobacteria had negative correlation to LDL-C level, but Cyanobacteria and Lentisphaerae had a positive correlation to LDL-C level. Moreover, gender and age were also found somehow correlated to microbial community composition.Conclusion: Rosuvastatin therapy had different blood lipid-lowering effect on hyperlipidemia. The gut microbiota exhibited variation in community composition, diversity and taxa in association to rosuvastatin hypolipidemic effect. These results indicate that modulation of gut microflora, especially the negative/positive correlated species might strengthen statin efficacy in statin-inadequate patients.

Rosuvastatin alters the genetic composition of the human gut microbiome

“…Little is known about the direct effect of statins on the human gut microbiota, except for associations with overall bacterial composition in a population-based study 12 , and some differences between patients with and without normalization of blood lipid levels 26 . Herein, rosuvastatin treatment was associated with a trend towards increasing gut microbial richness, as reported in studies of atorvastatin-treated rats 5 , while studies in mice have been unable to detect changes in fecal microbial diversity after rosuvastatin treatment 27,28 .…”

Eggshell membrane powder lowers plasma triglyceride and liver total cholesterol by modulating gut microbiota and accelerating lipid metabolism in high‐fat diet‐fed mice

“…Our analysis at the phylum level found that ESM supplementation reduced Firmicutes, but increased Bacteroidetes and Cyanobacteria abundance. It has been reported that the phylum Firmicutes is negatively correlated with LDL‐cholesterol (Liu et al, 2018). Additionally, increased Bacteroidetes abundance has been implicated in the reduction of TG levels (Caspi et al, 2016), while increased Cyanobacteria abundance has been observed during prebiotic treatment (Everard et al, 2014).…”

“…In addition, the occurrence of certain bacterial species during dietary intervention, such as Lactobacillus spp., positively affects insulin sensitivity and reduces plasma cholesterol levels in obese mice (Park et al, 2017). A recent study involving hyperlipidaemia patients receiving rosuvastatin treatment showed that the hypolipidemic effect was associated with a variation in gut microbiota composition (Liu et al, 2018).…”

An in vitro evaluation of the effects of different statins on the structure and function of human gut bacterial community

“…The patient's statin-sensitive responses are linked to the gut microbiota, and the gut microbiota may guide the statin dosage adjustments [54]. There are indeed several reports showing that statins influence the diversity of the human gut microbiota [18,[55][56][57]. In addition, although the research on the antibacterial activity of FLU has been scarce and more studies are needed [58], it seems that its antifungal activity may be higher than that of other statins [59].…”