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研究生: 趙盈婷
Ying-Ting Chao
論文名稱: 探討血液透析患者中腸胃道菌相之變化
Role o f T he G ut M icrobiota and I ts A ssociate d M etabolites in H emo dialysis P atients
指導教授: 許藝瓊
Yi-Chiung Hsu
口試委員:
學位類別: 博士
Doctor
系所名稱: 生醫理工學院 - 系統生物與生物資訊研究所
Graduate Institute of Systems Biology and Bioinformatics
論文出版年: 2023
畢業學年度: 111
語文別: 中文
論文頁數: 66
中文關鍵詞: 鈣磷積產物慢性腎臟疾病腸道微生物菌群失調
外文關鍵詞: calcium-phosphorus product, chronic kidney disease, gut microbiota, dysbiosis
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  • 心血管疾病為慢性腎病及末期腎病患者中相當常見的併發及死亡原因之一,其中血管鈣化為一個重要的危險因子。本研究探討腸道微生物群對於血管鈣化對於末期腎病患者心血管疾病的影響。實驗材料使用之糞便檢體,分別來自於健康對照組、控制良好鈣磷乘積產物的血液透析患者(HD)以及具有高鈣磷乘積產物的血液透析患者(HDHCP),並對這些組別進行了16S片段定序再進行後續腸道微生物組成分析。 結果顯示,腸道微生物組成在健康對照組和血液透析患者中存在著顯著差異。在血液透析患者的菌相中,厚壁菌門、放線菌門以及變形菌門在豐度上有明顯增加。而在高鈣磷乘積產物組中,厚壁菌門中的一種菌屬Lachnospiraceae_FCS020_group,比起其他組別,則有顯著的增加。除了偵測腸道微生物組成變化外,我們利用PICRUSt軟體來預測功能性分析,發現HDHCP組中有幾個與血管鈣化相關的代謝途徑明顯差異,包括糖醣磷酸途徑、類固醇及萜烯骨架生物合成途徑與脂肪酸鏈的延長合成的上調。我們的研究結果證明了腸道微生物菌相的改變以及其代謝物,在末期腎病患者血管鈣化過程中扮演著重要角色,並對鈣磷乘積產物的生成具有潛在影響。某些微生物的增加和特定代謝途徑可能會影響末期腎病患者中的血管鈣化程度。


    This study investigated the impact of gut microbiota on vascular calcification (VC), a cardiovascular risk factor in end-stage renal disease (ESRD). Fecal samples were collected from healthy controls, dialysis patients with controlled Ca x P, and dialysis patients with higher Ca x P (HDHCP). The samples were subjected to 16S amplicon sequencing to analyze the gut microbial composition. The results showed significant differences in gut microbial composition between hemodialysis patients and healthy controls. Three phyla (Firmicutes, Actinobacteria, and Proteobacteria) were notably more abundant in hemodialysis patients. Within the group with higher Ca x P, a specific genus called Lachnospiraceae_FCS020_group was significantly increased. Serval metabolic pathway, as predicted by the PICRUSt software, including the pentose phosphate pathway, the steroid biosynthesis pathway, the terpenoid backbone biosynthesis pathway and fatty acid elongation pathway, were found to be upregulated in the higher Ca x P group. Our research highlights the significance of dysbiosis in the gut microbiome of hemodialysis patients and its potential influence on Ca x P levels. We observed an elevated presence of specific microbial taxa and the upregulation of certain metabolic pathways. These findings suggest that these factors may play a role in the development of VC, a known cardiovascular risk factor in individuals with ESRD.

    中 文 摘 要 I ABSTRACT II 謝 辭 III Contents IV List of Figures V List of Tables VI Chapter II Materials and methods 9 2-1 Patients and Controls 9 2-2 Stool DNA extraction and 16S rRNA gene amplification 10 2-3 16S rRNA Gene Amplicon Sequencing 11 2-4 Bioinformatics and statistical analysis 12 Chapter III Results 15 3-1 Characteristics of the participants in the clinical study 15 3-2 Comparison of gut microbial diversity between healthy controls and hemodialysis patients 16 3-3 Comparison of the gut microbiome composition in healthy controls and hemodialysis patients 18 3-4 Potential bacterial species associated with higher Ca xP levels in hemodialysis patients 20 3-5 Correlation between the gut microbiome and clinical indicators in hemodialysis patients 22 3-6 Identification of crucial microbial functions associated with Ca xP levels in dialysis patients 22 Chapter IV Discussion 24 Chapter V Conclusion 33 Chapter VI Bibliography 34 Chapter VII Tables 44 Chapter VIII Figures 49 Appendix 58

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