Document Details
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Document Type |
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Thesis |
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Document Title |
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COMPARISON BETWEEN DYSBIOSIS IN GUT MICROBIOTA OF DYSLIPIDEMIC PATIENTS AND RATS, AND THE IMPACT OF ANTI –LIPIDEMIC DRUGS مقارنة بين ميكروبات القناة الهضمية في مرضى خلل تمثيل الدهون والجرذان وتأثير العقاقير المضادة لزيادة الدهون |
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Subject |
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Faculty of Sciences |
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Document Language |
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Arabic |
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Abstract |
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Hypercholesterolemia is known as one of the important risk factors for the development of cardiovascular diseases (CVD). The composition of gut microbiota (GM) influences cholesterol and lipid metabolism, but the effect of GM in the context of hypercholesterolemia and treatment with atorvastatin (a cholesterol-lowering drug) is unknown. The species composition of the GM is emerging as a key factor in the development of metabolic disorders. The aim of this study was to investigate the alteration in GM due to hypercholesterolemia and with atorvastatin administration, a commonly prescribed HMG-CoA reductase inhibitor. This study was divided into two studies, i.e., i) Animal study and, ii) Human study. In the animal study, 7 experimental groups were developed, based on diet (normal chow diet [NCD] and high-fat diet [HFD]), and atorvastatin treatment [NCD-T (10 mg/kg), HFD-5 mg/kg, HFD-10 mg/kg, HFD-15 mg/kg and HFD-20 mg/kg] in rats. Whereas, in the human study; 3 groups including hypercholesterolemic patients (HP) and atorvastatin-treated hypercholesterolemic patients (At-HP) relative to healthy subjects (HS) were included. 16S rRNA metagenomic sequencing was employed to analyze the GM. The atorvastatin treatment shifted the structure and diversity of GM in both the human and animal model. The GM structure was substantially modulated along with increased bacterial diversity, in atorvastatin-treated HFD and NCD group, then HFD control. Whereas, the bacterial diversity was greater among HP but lower in the At-HP group. Significantly reduced cholesterol level was observed under dose-dependent atorvastatin treatment. Atorvastatin-treatment reduced the Firmicutes/Bacteroidetes ratio, while increased the abundance of Proteobacteria in HFD rats. Dominant taxa include Prevotella, Paraprevotella, Oscillospira, Paraprevotella clara, Prevotella copri, Bacteroides sartorii, Prevotella dentasini and Bacteroides coprocola, showed reverted growth in drug-treated HFD group. The Oscillospira eae and Desulfovibrio piger, exhibited a similar growth response, after atorvastatin treatment to HFD and NCD group. In HP, the relative growth of atherosclerosis (AS)-associated taxa such as Collinsella and Streptococcus was up-regulated, whereas anti-inflammatory/beneficial taxa, including Faecalibacterium prausnitzii, Akkermansia muciniphila, and genus Oscillospira, had lower abundance compared with At-HP. In addition, the abundance of Desulfovibrio sp., a pro-inflammatory taxon, and Bilophila wadsworthia and Bifidobacterium bifidum, both bile acid–associated operational taxonomic units (OTUs), were reduced in At-HP compared with HP.
Based on Spearman correlation analysis, a negative correlation (ρ>−0.26) with total serum cholesterol and low-density lipoprotein (LDL) -cholesterol level existed for Faecalibacterium sp., Faecalibacterium prausnitzii, and Akkermansia muciniphila, but the correlation (ρ> −0.28) with high-density lipoprotein (HDL)-cholesterol was positive. The GM composition in the HP group was altered, and the taxa that were dysbiotic in the HP group showed significant resilience in the At-HP group. In conclusion, atorvastatin intake causes GM alteration, particularly among taxa associated with bile acid, AS, and inflammation. An overall increased abundance of anti-inflammatory bacteria along with the reduced growth of pro-inflammatory taxa was observed in At-HP. Our animal study highlighted, a pattern in the growth of selective bacteria under dose-dependent atorvastatin treatment, the reduced bacterial diversity and the modulation of an overall GM, along with the growth of some beneficial taxa, that suggests the impact of the drug on the GM of the host.
Key words: Gut microbiota, Atorvastatin, High fat diet, Hypercholesterolemia |
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Supervisor |
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Dr. Yousry Mohammed Suleiman |
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Thesis Type |
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Doctorate Thesis |
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Publishing Year |
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1438 AH
2017 AD |
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Added Date |
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Tuesday, May 30, 2017 |
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Researchers
| طارق جمال خان | Khan, Tariq Jamal | Researcher | Doctorate | |
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