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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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5874287 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Gut Microbiome Associates With Lipid-Lowering Effect of Rosuvastatin <i>in Vivo</i>.

Liu Yinhui Y Song Xiaobo X Zhou Huimin H Zhou Xue X Xia Yunlong Y Dong Xin X Zhong Wei W Tang Shaoying S Wang Lili L Wen Shu S Xiao Jing J Tang Li L

Frontiers in microbiology 20180322

<b>Background:</b> 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.<h4>Trial registration</h4>ChiCTR-ORC-17013212 at the First Affiliated Hospital of Dalian Medical University, November 2, 2017. <b>Results:</b> Totally 64 patients with hyperlip ...[more]

PMID: 29623075

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Project description:Background - Prepregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, during pregnancy the impact of overweight on immune cell gene expression and its association with maternal and infant outcomes is not well explored. Methods – Blood samples were collected from healthy normal weight (NW, BMI 18.5-24.9) or overweight (OW, BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. Results - Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2’FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. Conclusions – These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Further, deciphering the complex association of PBMC’s gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.

Project description:BackgroundRosuvastatin is a lipid-lowering agent widely prescribed in people living with HIV, which is actively transported into the liver, making it a potential victim of drug-drug interactions with antiretroviral agents.ObjectivesThe aims of this study were to characterise the pharmacokinetic profile of rosuvastatin and to describe the relationship between rosuvastatin concentrations and non-high-density lipoprotein (HDL)-cholesterol levels in people living with HIV.MethodsA population pharmacokinetic model (NONMEM) was developed to quantify the influence of demographics, clinical characteristics and comedications on rosuvastatin pharmacokinetics. This model was combined with an indirect effect model to describe non-HDL-cholesterol measurements.ResultsA two-compartment model with sequential zero- and first-order absorption best fitted the 154 rosuvastatin concentrations provided by 65 people living with HIV. None of the tested covariates significantly influenced rosuvastatin pharmacokinetics. A total of 403 non-HDL cholesterol values were available for pharmacokinetic-pharmacodynamic modelling. Baseline non-HDL cholesterol decreased by 14% and increased by 12% with etravirine and antiretroviral drugs with a known impact on the lipid profile (i.e. protease inhibitors, efavirenz, cobicistat), respectively. The baseline value was surprisingly 43% lower in people living with HIV aged 80 years compared with those aged 40 years. Simulations based on the covariate-free model predicted that, under standard rosuvastatin dosages of 5 mg and 20 mg once daily, 31% and 64% of people living with HIV would achieve non-HDL-cholesterol targets, respectively.ConclusionsThe high between-subject variability that characterises both rosuvastatin pharmacokinetic and pharmacodynamic profiles remained unexplained after the inclusion of usual covariates. Considering its limited potential for drug-drug interactions with antiretroviral agents and its potent lipid-lowering effect, rosuvastatin prescription appears safe and effective in people living with HIV with hypercholesterolaemia.Clinical trial registration noNCT03515772.

Project description:The association between gut microbiome and chronic metabolic disease including polycystic ovary syndrome (PCOS), is well documented, however, the relationship between the gut microbiota and serum metabolites remains unknown. In this study, untargeted metabolomics together with a 16S rRNA gene sequencing tool was used to detect small molecule serum metabolites and the gut microbiome. We identified 15 differential metabolites between PCOS patients and the healthy control. Lysophosphatidylcholine (LPC) (18:2, 20:3, 18:1, P-16:0, 17:0, 15:0, 18:3, 20:4), phosphatidylcholine(PC), ganglioside GA2 (d18:1/16:0) and 1-linoleoylglycerophosphocholine were increased in the PCOS group, and the concentrations of phosphoniodidous acid, bilirubin, nicotinate beta-D-ribonucleotide and citric acid were decreased in the PCOS group, suggesting a lipid metabolism and energy metabolism disorder in the PCOS patients. The diversity of gut microbiota in PCOS group was lower than that in healthy controls. Escherichia/Shigella, Alistipes and an unnamed strain 0319_6G20 belonging to Proteobacteria were important distinguishing genera (LDA > 3.5) in PCOS. Prevotella_9 was positively correlated with phosphoniodidous acid, nicotinate beta-D-ribonucleotide and citric acid concentrations, and negatively correlated with the concentration of LPC (20:3) and 1-linoleoylglycerophosphocholine; Roseburia was negatively correlated with LPC concentration (20:4), while the characteristic genus 0319_6G20 of PCOS was positively correlated with LPC concentration (20:3) (COR > 0.45). SF-36 in the PCOS group was significantly lower than that in the healthy control (HC) group, which was associated with the presence of Escherichia-Shigella and Alistipes. Our finding demonstrated the correlation between the gut microbiota and serum metabolites in PCOS, and therefore characteristic gut microbiota and metabolites may play an important role in the insulin resistance and the mood changes of PCOS patients.

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

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Gut Microbiome Associates With Lipid-Lowering Effect of Rosuvastatin <i>in Vivo</i>.

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