Effect of atorvastatin on the gut microbiota of high fat diet-induced hypercholesterolemic rats

Khan, Tariq Jamal; Ahmed, Youssri; Zamzami, Mazin A.; Mohamed, Saleh A.; Khan, Imran; Baothman, Othman A.; Mehanna, Mohamed G.; Yasir, Muhammad

doi:10.1038/s41598-017-19013-2

Cited by 97 publications

(92 citation statements)

References 52 publications

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“…The genus Helicobacter, a potential producer of intracellular reactive oxygen species and MDA, induces gastric inflammation and gastrointestinal infection [37,38]. Moreover, an elevated abundance of Clostridium and SMB53 due to an HFD was in agreement with a previous report [39].…”

Section: Discussionsupporting

confidence: 90%

Astaxanthin n-Octanoic Acid Diester Ameliorates Insulin Resistance and Modulates Gut Microbiota in High-Fat and High-Sucrose Diet-Fed Mice

Gao

Yang

Chin

et al. 2020

IJMS

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Astaxanthin n-octanoic acid diester (AOD) is a type of astaxanthin connecting medium-chain fatty acids with a more stable structure. In this study, we examined the role of AOD in ameliorating insulin resistance (IR) induced by a high-fat and high-sucrose diet (HFD) as well as its effect on modulating gut microbiota in mice, with free astaxanthin (AST) as a comparison. Four groups of male C57BL/6J mice (6 weeks old; n = 10 per group) were fed with a normal control diet (NC), HFD orally administered with AOD, AST (50 mg/kg body weight), or vehicle for 8 weeks. AOD improved glucose tolerance, IR, systematic and intestinal inflammation, and intestinal integrity better than AST. Further, both AOD and AST modulated gut microbiota. A significantly higher abundance of Bacteroides and Coprococcus was found in AOD than in AST, and the predicted pathway of carbohydrate metabolism was significantly impacted by AOD. Overall, AOD may play a role in alleviating IR and inflammation with the modulating effect on microbiota in HFD-fed mice. Our findings could facilitate the development of AOD as a bioactive nutraceutical and more stable alternative to AST.

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Section: Discussionsupporting

confidence: 90%

Astaxanthin n-Octanoic Acid Diester Ameliorates Insulin Resistance and Modulates Gut Microbiota in High-Fat and High-Sucrose Diet-Fed Mice

Gao

Yang

Chin

et al. 2020

IJMS

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“…Ruminococcus is a genus reversed uniquely by ATO and its reversion by ATO was also reported in a previous study. 15 Lower levels of Ruminococcus are associated with higher levels of CRP and IL-6. However, another study found that the abundance of Rumicoccus gnavus was higher in ACDV patients compared with controls.…”

Section: Discussionmentioning

confidence: 98%

“…The dose of administration of ATO and strains were determined by referring to previous studies and was verified by preliminary experiments. 6,15…”

Section: Methodsmentioning

confidence: 99%

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Probiotic strains improve high-fat diet-induced hypercholesterolemia through modulating gut microbiota in ways different from atorvastatin

Liu

Chen

et al. 2019

Preprint

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Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Probiotics is one of the most popular dietary supplements for hypercholesterolemia, but there are questions as to whether there are differences between probiotics and cholesterol-lowering drugs as like atorvastatin (ATO) both in effectiveness and the underlying mechanisms. In this study, the hypocholesterolemia effects of 4 probiotic strains were investigated and compared with ATO, focusing on their impacts on gut microbiota. Hypercholesterolemia model was established via high-fat diet (HFD) in golden hamsters after which ATO and the 4 probiotics were orally administered individually for 8 weeks. All probiotics were effective, but less than ATO, both on body weight, serum parameters (TG, TC, LDL, INS, HbA1c) and expression of inflammatory factors (TNF-α, IL-1β, CRP), with strain JQII-5 most significant. Besides, these effects were associated with restoration of the microbiota dysbiosis induced by HFD. It was worth noting that ATO and probiotics induced different shifts of gut microbiota in both structure and key phylotypes. Most interestingly, Allobaculum, a HFD-suppressed genus, reported to be involved in alleviating oxidative stress, was enriched by all tested probiotic strains, but not by ATO. Furthermore, Prevotella, also a HFD-suppressed genus, was uniquely reversed by JQII-5. Importantly, most of the alerted genus and reversed genus was found to be correlated to inflammatory state and serum lipid level. Compared with ATO, probiotic strains were less effective on body weight, hypercholesterolemia, and inflammation. However, probiotics exert additional favorable effects on gut microbiota, making them excellent potential complements to cholesterol-lowering drugs like ATO.

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“…The interactions between exercise and vitamin D status with statin use warrant further study. Increased research is also needed into the gut microbiome, as it has recently been shown to be significantly perturbed by statins [278,279] and might module statin response [280]. Much has been done; much work remains.…”

Section: Discussionmentioning

confidence: 99%

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Turner

Pirmohamed

2019

JCM

146

126

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Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, a small subset of patients experience statin-related myotoxicity (SRM). SRM is heterogeneous in presentation; phenotypes include the relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing SRM in clinical practice can be challenging, particularly for mild SRM that is frequently due to alternative aetiologies and the nocebo effect. Nevertheless, SRM can directly harm patients and lead to statin discontinuation/non-adherence, which increases the risk of cardiovascular events. Several factors increase systemic statin exposure and predispose to SRM, including advanced age, concomitant medications, and the nonsynonymous variant, rs4149056, in SLCO1B1, which encodes the hepatic sinusoidal transporter, OATP1B1. Increased exposure of skeletal muscle to statins increases the risk of mitochondrial dysfunction, calcium signalling disruption, reduced prenylation, atrogin-1 mediated atrophy and pro-apoptotic signalling. Rare variants in several metabolic myopathy genes including CACNA1S, CPT2, LPIN1, PYGM and RYR1 increase myopathy/rhabdomyolysis risk following statin exposure. The immune system is implicated in both conventional statin intolerance/myotoxicity via LILRB5 rs12975366, and a strong association exists between HLA-DRB1*11:01 and anti-HMGCR positive myopathy. Epigenetic factors (miR-499-5p, miR-145) have also been implicated in statin myotoxicity. SRM remains a challenge to the safe and effective use of statins, although consensus strategies to manage SRM have been proposed. Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight.

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Effect of atorvastatin on the gut microbiota of high fat diet-induced hypercholesterolemic rats

Cited by 97 publications

References 52 publications

Astaxanthin n-Octanoic Acid Diester Ameliorates Insulin Resistance and Modulates Gut Microbiota in High-Fat and High-Sucrose Diet-Fed Mice

Astaxanthin n-Octanoic Acid Diester Ameliorates Insulin Resistance and Modulates Gut Microbiota in High-Fat and High-Sucrose Diet-Fed Mice

Probiotic strains improve high-fat diet-induced hypercholesterolemia through modulating gut microbiota in ways different from atorvastatin

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

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