Red yeast rice ameliorates high-fat diet-induced atherosclerosis in Apoe−/− mice in association with improved inflammation and altered gut microbiota composition

Dong, Yanhan; Cheng, Huimin; Liu, Ying; Xue, Meilan; Liang, Hui

doi:10.1039/c9fo00583h

Cited by 41 publications

(35 citation statements)

References 49 publications

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“…40,42,43 On the other hand, the relative abundance of Flavonifractor has a positive correlation with inflammation cytokines, like interleukin, cholesterol and LDL levels in plasma. 44,45 Flavonifractor may cleave the flavonoid C-ring and degenerate quercetin to increase oxidative stress and trigger inflammatory markers such as C5a, IL-6, IL-7, IL-8, IL-1β and IL-21. 46 Notably, by obstructing the insulin signal transduction, IL-6 can induce insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Phocea, Pseudoflavonifractor and Lactobacillus intestinalis: Three Potential Biomarkers of Gut Microbiota That Affect Progression and Complications of Obesity-Induced Type 2 Diabetes Mellitus

Wang¹,

Ouyang²,

Gao³

et al. 2020

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The purpose of this study was to explore the difference and association between intestinal microbiota and plasma metabolomics between type 2 diabetes mellitus (T2DM) and normal group and to identify potential microbiota biomarkers that contribute the most to the difference in metabolites. Methods: Six male ZDF model (fa/fa) rats were fed by a Purina #5008 Lab Diet (crude protein 23.5%, crude fat 6.5%) for 3 weeks and their age-matched 6 ZDF control (fa/+) rats were fed by normal rodent diet. Their stool and blood samples were collected at 12 weeks. To analyze the microbial populations in these samples, we used a 16S rRNA gene sequencing approach. Liquid chromatography-mass spectrometry (LC-MS) followed by multivariate statistical analysis was applied to the plasma metabolites profiling. Correlation analysis of them was calculated by Pearson statistical method. Results: Twelve potential biomarkers of intestinal microbial flora and 357 differential metabolites were found in ZDF fa/fa rats, among which there are three flora that contributed the most to the perturbation of metabolites, including genus Phocea, Pseudoflavonifractor and species Lactobacillus intestinalis. Conclusion: Our study demonstrates the alterations of the abundance and diversity of the intestinal microbiota and the perturbation of metabolites in ZDF rats (fa/fa). We found three potential biomarkers of intestinal microbiota that may lead to perturbation in plasma metabolites. This may prompt new pathogenesis of obesity-related T2DM, but we also need to study further about the causal relationship between intestinal microbe and T2DM, so as to find the target of T2DM treatment or preventive measures.

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Section: Discussionmentioning

confidence: 99%

Phocea, Pseudoflavonifractor and Lactobacillus intestinalis: Three Potential Biomarkers of Gut Microbiota That Affect Progression and Complications of Obesity-Induced Type 2 Diabetes Mellitus

Wang¹,

Ouyang²,

Gao³

et al. 2020

DMSO

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“…Pathological conditions may arise when the host’s metabolic, immune and inflammatory reactions are influenced by an imbalance in the gut microbiome (dysbiosis). Moreover, evidence suggests that the gut microbiota play a role in CVD (Dong et al ). Atherosclerosis is characterized by the development of chronic inflammation over decades, and lesion formation is promoted by the build‐up of cholesterol on artery walls (Abbott et al ).…”

Section: Introductionmentioning

confidence: 99%

Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites

et al. 2019

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Aims Epidemiological studies have correlated cardiovascular disease and atherosclerosis with lifestyle factors such as sedentary behaviour and a high‐calorie diet. Recent studies of pathogenesis have highlighted the significance of the intestinal microbiota and chronic inflammation with respect to both the onset and development of atherosclerosis. This study examined the hypothesis that the oral administration of quercetin to low‐density lipoprotein receptor‐null (Ldlr−/−) mice would improve gut health by altering the gut microbiota and controlling the levels of atherogenic lipid metabolites and proinflammatory mediators in the intestine and serum. Methods and Results Mice were maintained on a high‐fat diet with or without oral quercetin administration for 12 weeks. Quercetin treatment suppressed body weight gains and reduced the extent of atherosclerotic lesions in the aortic sinus. Reduced malondialdehyde and increased interleukin 6 levels further indicated the protective effect of quercetin against immune/inflammatory responses and oxidative stress. Furthermore, quercetin led to decreased intestinal levels of cholesterol, lysophosphatidic acids and atherogenic lysophosphatidylcholine (LPC 18:1) and an increased level of coprostanol. A phylum‐level microbial analysis revealed that quercetin treatment reduced the abundance of Verrocomicrobia and increased microbiome diversity and the abundances of Actinobacteria, Cyanobacteria and Firmicutes. A Spearman analysis revealed negative correlations of Actinobacteria with intestinal and plasma LPC 18:1 and caecal cholesterol levels and of Firmicutes and Cyanobacteria with the plasma LPC 18:1 level. Conclusions This study demonstrated the ability of quercetin treatment to reduce lipid levels, as well as the areas of atherosclerotic lesions and sizes of plaques. This treatment also altered the composition of the gut microbiota and decreased the levels of atherogenic lipid metabolites. Significance and Impact of the Study Oral quercetin treatment may represent a new approach to mitigating the onset and development of atherosclerosis.

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“…At the level of phylum, more than 90% of the microbial populations in each group consisted of Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria when compared to the given percentage of the relative abundance ( Figures 6A, C ). Compared with the NC group (55.95 ± 13.15%), the HFD group (82.78 ± 4.13%) exhibited a markedly increased abundance of Firmicutes (p < 0.05), which often enhanced the risk of AS and obesity ( Rom et al., 2017 ; Dong et al., 2019 ; Ozato et al., 2019 ). After AOB treatment, the abundance of Firmicutes showed a decreasing trend (63.84 ± 15.10%).…”

Section: Resultsmentioning

confidence: 96%

Alisma orientalis Beverage Treats Atherosclerosis by Regulating Gut Microbiota in ApoE-/- Mice

Zhu

Zhai

et al. 2020

Front. Pharmacol.

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Background: Alisma orientalis beverage (AOB) is a Chinese traditional medicine formulated with a diversity of medicinal plants and used for treating metabolic syndrome and atherosclerosis (AS) since time ago. Given the current limited biological research on AOB, the mechanism by which AOB treats AS is unknown. This study investigats the role of AOB-induced gut microbiota regulation in the expansion of AS. Methods: We established an AS model in male apolipoprotein E-deficient (ApoE −/−) mice that are fed with a high-fat diet (HFD), treated with numerous interventions, and evaluated the inflammatory cytokines and serum biochemical indices. The root of the aorta was stained with oil red O, and the proportion of the lesion area was quantified. Trimethylamine N-oxide (TMAO) and trimethylamine (TMA) levels in serum were evaluated through liquid chromatography with mass spectrometry. Flavin−containing monooxygenase 3 (FMO3) liver protein expression was assessed by Western blotting. 16S rDNA sequencing technique was adopted to establish the changes in the microbiota structure. Results: After 8 weeks of HFD feeding, an inflammatory cytokine, and AS development expression were significantly decreased in mice treated with AOB; the same parameters in the mice treated with the antibiotics cocktail did not change. In the gut microbiota study, mice treated with AOB had a markedly different gut microbiota than the HFD-fed mice. Additionally, AOB also decreased serum TMAO and hepatic FMO3 expression. Conclusion: The antiatherosclerotic effects of AOB were found associated with changes in the content of gut microbiota and a reduction in TMAO, a gut microbiota metabolite, suggesting that AOB has potential therapeutic value in the treatment of AS.

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Red yeast rice ameliorates high-fat diet-induced atherosclerosis in Apoe^−/− mice in association with improved inflammation and altered gut microbiota composition

Abstract: Red yeast rice could significantly protect against atherosclerosis, which were possibly associated with the alterations in the gut microbiota composition.

Cited by 41 publications

References 49 publications

<p><em>Phocea</em>, <em>Pseudoflavonifractor</em> and <em>Lactobacillus intestinalis</em>: Three Potential Biomarkers of Gut Microbiota That Affect Progression and Complications of Obesity-Induced Type 2 Diabetes Mellitus</p>

<p><em>Phocea</em>, <em>Pseudoflavonifractor</em> and <em>Lactobacillus intestinalis</em>: Three Potential Biomarkers of Gut Microbiota That Affect Progression and Complications of Obesity-Induced Type 2 Diabetes Mellitus</p>

Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites

Alisma orientalis Beverage Treats Atherosclerosis by Regulating Gut Microbiota in ApoE-/- Mice

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