研究生: |
張可寯 Chang, Ko-Chun |
---|---|
論文名稱: |
呼吸道過敏兒童之腸道微生物測序及糞便代謝體綜合性分析 Integrated analysis of gut metagenomic and fecal metabolomic data for childhood airway allergies |
指導教授: |
謝文萍
Hsieh, Wen-Ping |
口試委員: |
蘇仕奇
Su, Shih-Chi 鍾仁華 Chung, Ren-Hua 邱志勇 Chiu, Chih-Yung |
學位類別: |
碩士 Master |
系所名稱: |
理學院 - 統計學研究所 Institute of Statistics |
論文出版年: | 2022 |
畢業學年度: | 110 |
語文別: | 英文 |
論文頁數: | 67 |
中文關鍵詞: | 兒童呼吸道過敏 、總基因體學 、腸道微生物菌相 、糞便代謝體 |
外文關鍵詞: | Childhood airway allergies, Metagenomics, Gut microbiome, Fecal metabolites |
相關次數: | 點閱:1 下載:0 |
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氣喘是兒童最常見的慢性疾病的一種,是指支氣管出現慢性發炎後出現過度反應的問題且主 要好發於兒童。而近年來有多項研究指出腸道菌叢的變化與氣喘息息相關,腸道菌代謝所產 生的衍生物會影響呼吸道的發炎反應。本研究中,我們蒐集了 84 位孩童樣本分別是 25 位鼻 炎、31 位氣喘以及 28 位健康對照組,對其臨床指標、腸道微生物、糞便代謝體與腸道微生 物功能建立一套完整的綜合性分析。首先,我們對腸道微生物進行多樣性分析,藉由 α 多樣 性分析樣本間的差異,β 多樣性分析各組間的差異並利用多維尺度進行視覺化呈現。接者利 用機器學習方法對腸道微生物與糞便代謝體進行特徵選擇,藉此找出具有代表性的生物標 記。再來藉由 Canonical Correspondence analysis 與 Co-inertia analysis 對腸道微生物與糞便 代謝體中具代表性的變數進行關聯性分析。
我們發現在氣喘病患腸道中的碳水化合物活性酵素 (CAZyme) 基因的數量及豐富度隨著 其物種多樣性減少而減少,這與碳水化合物活性酵素相關的丁酸鹽 (butyrate) 減少結果一 致。此外,我們從抗藥性與致病毒素中找到特定表型與氣喘相關。綜合以上分析,我們對孩 童的腸道微生物、糞便代謝體與腸道微生物功能彼此間的關聯性有更深層的理解,這會對氣 喘病患的治療與診斷有一定程度的助益。
Airway allergic diseases, such as allergic rhinitis and asthma, are among the most common chronic diseases in children. It is an overreaction to irritants after chronic inflammation of the bronchi and mainly occurs to children. In recent years, several studies have pointed out that the changes in the intestinal flora are closely related to asthma, and the derivatives produced by the metabolism of intestinal bacteria can affect the inflammatory response of the respiratory tract. In this study, we collected samples in a cohort of children with mite-sensitized airway allergies (25 with rhinitis and 31 with asthma) and 28 non-allergic healthy controls, to establish an integrated analysis of clinical indices, gut microbiome, fecal metabolites and gut microbiome functions. We first computed the biodiversity of gut microbiome to explore the differences be- tween samples and between groups. Moreover, we use machine learning methods to perform feature selection on the gut microbiome and fecal metabolites to identify biomarkers. In addi- tion, the correlation analysis of selected variables in the gut microbiome and fecal metabolites was performed by Canonical correspondence analysis and Co-inertia analysis.
We found that the number and abundance of carbohydrate-active enzyme (CAZyme) genes in the gut of patients with asthma decreased as their species diversity decreased, which is consistent with the CAZyme-related butyrate reduction. In addition, we identified specific phenotypes associated with asthma from gut resistome and virulome. Based on the above analysis, we gain a much more profound understanding of the relationship between the gut microbiome, fecal metabolites, and gut microbiome functions, which will bring benefit to the treatment and diagnosis of asthma patients.
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