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研究生:林介友
研究生(外文):Lin, Chieh-Yu
論文名稱:插管對人體口咽部與氣管內微生物菌相之影響探討
論文名稱(外文):The influence of intubation on the microbiota of oropharynx and trachea
指導教授:謝文萍
指導教授(外文):Hsieh, Wen-Ping
口試委員:徐南蓉藍忠昱
口試委員(外文):Hsu, Nan-JungLan, Chung-Yu
口試日期:2018-01-11
學位類別:碩士
校院名稱:國立清華大學
系所名稱:統計學研究所
學門:數學及統計學門
學類:統計學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:中文
論文頁數:41
中文關鍵詞:負二項迴歸插管人體微生物菌相
外文關鍵詞:Negativebinomialregressionintubationmicrobiota16SrDNA
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呼吸道重症患者因為無法自主呼吸可能需要進行插管與安裝呼吸器,研究顯示甫插管2週的患者是感染呼吸器相關肺炎(ventilator associated pneumonia, VAP)的高風險群,甚至可能因此死亡,儘管已經知道造成VAP的原因是微生物菌相(microbiota),但是微生物群包含了病毒、細菌與真菌,而且有些微生物無法以樣本培養的方式分離出,以至於無法得知主要是那些微生物造成VAP感染。
本研究分析從研究人員蒐集而來的5位插管病患資料,資料以基因定序(sequenceing)的方式調查出樣本的16S rDNA基因序列是來自哪種細菌,並嘗試以資料視覺化與負二項分布的廣義線性模型來觀察這些病患體內之細菌是如何隨插管改變的,從中推測造成感染的細菌為那些。
在長條圖中看出插管後Proteobacteria與Tenericutes的細菌於部分樣本中有增加的情況,而Firmicutes則在大多樣本中發現減少,在模型分析中也發現Firmicutes的細菌只有負的插管效應顯著,表示插管後數量顯著地減少。這些細菌數量的增減可能反映了造成感染疾病的細菌是那些,然而研究中因為樣本數的不足而未能將所有差異因素考慮於分析中,所以無法更全面地解釋細菌數量改變的原因。
Patients with respiratory disease are usually provided with endotracheal tube due to respiratory obstacle. Many studies show that they are risky to be infected by ventilator associated pneumonia (VAP). VAP may cause death results from the invasion of the lower respiratory tract and lung parenchyma by microorganisms (virus, bacteria, or fungi). It is difficult for researchers to find out what microorganisms lead to VAP because some of the microorganisms are culture independent.

This study analyzed 5 patients who were intubated in ICU. The data are genetic sequence counts from 16S rDNA which can be matched with bacteria species information. This study provides data vidualizrions and adopts the negative binomial regression model to understand the variation of bacteria counts during intubation and inferred the pathogenic bacteria at VAP.According to the bar plots, Proteobacteria and Tenericutes increased after intubation at several parts of the samples. Firmicutes all decreased after intubation and their effects were all significantly negative as well.
摘要……………………….………………………………….……..…...…....P3
第一章 緒論…………………………………………………….…..…...…...P5
第二章 研究流程與方法……………………………………….…….……...P7
第一節 資料介紹說明………………………………………..…………P7
第二節 負二項迴歸模型建立、研究流程…………………….……….P7
第三章 結果………………………………………………………………...P11
第一節 細菌種類分析結果與數量變化探討…………………………P11
第二節 負二項迴歸模型檢定結果……………………………………P11
第四章 問題討論…………………………………………………………...P13
第一節 關於插管病患的口咽部與氣管細菌數量減少之探討………P13
第二節 插管效應顯著的細菌物種與疾病關聯………………………P14
第五章 結論……………………………...………….……………………...P15
附圖………...…………………………………………………….........P16~P27
附表………...…………………………………………………….........P28~P40
參考文獻……………………………………………………………….........P40
Alp, E. and Voss, A. Ventilator associated pneumonia and infection control. Annals of Clinical Microbiology and Antimicrobials 2006;5:7-7.
Bardes, J.M., et al. The Prevalence of Oral Flora in the Biofilm Microbiota of the Endotracheal Tube. The American Surgeon 2016;82(5):4.
Cameron, A.C. and Trivedi, P.K. Regression analysis of count data. 2013.
Cani, P.D., et al. Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes 2007;56(7):1761.
Chen, W., et al. Human Intestinal Lumen and Mucosa-Associated Microbiota in Patients with Colorectal Cancer. PLoS ONE 2012;7(6):e39743.
David, L.A., et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2013;505:559.
Fang, R., et al. Zero-inflated negative binomial mixed model: an application to two microbial organisms important in oesophagitis. Epidemiology and Infection 2016;144(11):2447-2455.
Iwai, S., et al. Oral and Airway Microbiota in HIV-Infected Pneumonia Patients. Journal of Clinical Microbiology 2012;50(9):2995-3002.
Joyce, S.A., et al. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proceedings of the National Academy of Sciences of the United States of America 2014;111(20):7421-7426.
Kelly, B.J., et al. Composition and dynamics of the respiratory tract microbiome in intubated patients. Microbiome 2016;4:7.
Levine, S. and Niederman, M. The impact of tracheal intubation on host defenses and risks for nosocomial pneumonia. 1991.
Lohmann, P., et al. The airway microbiome of intubated premature infants: characteristics and changes that predict the development of bronchopulmonary dysplasia. Pediatric Research 2014;76:294.
Mariat, D., et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiology 2009;9(1):123.
Paulose, J.K., et al. Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity. PLOS ONE 2016;11(1):e0146643.
Ramphal, R., et al. Adherence of Pseudomonas aeruginosa to tracheal cells injured by influenza infection or by endotracheal intubation. Infection and Immunity 1980;27(2):614-619.
Voigt, R.M., et al. Circadian Disorganization Alters Intestinal Microbiota. PLoS ONE 2014;9(5):e97500.
Zarrinpar, A., et al. Diet and Feeding Pattern Affect the Diurnal Dynamics of the Gut Microbiome. Cell metabolism 2014;20(6):1006-1017.
Zhang, X., et al. Negative binomial mixed models for analyzing microbiome count data. BMC Bioinformatics 2017;18:4.
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