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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 臨床醫學研究所
Please use this identifier to cite or link to this item: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81135
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dc.contributor.advisor劉志銘(Jyh-Ming Liou)
dc.contributor.authorWen-Tsung Heen
dc.contributor.author何汶璁zh_TW
dc.date.accessioned2022-11-24T03:32:22Z-
dc.date.available2021-10-01
dc.date.available2022-11-24T03:32:22Z-
dc.date.copyright2021-10-01
dc.date.issued2021
dc.date.submitted2021-08-19
dc.identifier.citation1. Tsoi KKF, Pau CYY, Wu WKK, Chan FKL, Griffiths S, Sung JJY. Cigarette smoking and the risk of colorectal cancer: a meta-analysis of prospective cohort studies. Clin Gastroenterol Hepatol. 2009;7(6):682- 688.e1-5. doi:10.1016/j.cgh.2009.02.016 2. Giovannucci E, Rimm EB, Stampfer MJ, et al. A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. men. J Natl Cancer Inst. 1994;86(3):183-191. doi:10.1093/jnci/86.3.183 3. Terry P, Ekbom A, Lichtenstein P, Feychting M, Wolk A. Long-term tobacco smoking and colorectal cancer in a prospective cohort study. Int J Cancer. 2001;91(4):585-587. doi:10.1002/1097- 0215(200002)9999:9999<::aid-ijc1086>3.0.co;2-h 4. Biedermann L, Zeitz J, Mwinyi J, et al. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans. PLoS One. 2013;8(3):e59260. doi:10.1371/journal.pone.0059260 5. Lee SH, Yun Y, Kim SJ, et al. Association between Cigarette Smoking Status and Composition of Gut Microbiota: Population-Based Cross- Sectional Study. J Clin Med. 2018;7(9). doi:10.3390/jcm7090282 6. Wu J, Peters BA, Dominianni C, et al. Cigarette smoking and the oral microbiome in a large study of American adults. ISME J. 2016;10(10):2435-2446. doi:10.1038/ismej.2016.37 7. Vogtmann E, Flores R, Yu G, et al. Association between tobacco use and the upper gastrointestinal microbiome among Chinese men. Cancer Causes Control. 2015;26(4):581-588. doi:10.1007/s10552-015-0535-2 8. Borges-Canha M, Portela-Cidade JP, Dinis-Ribeiro M, Leite-Moreira AF, Pimentel-Nunes P. Role of colonic microbiota in colorectal carcinogenesis: a systematic review. Rev Esp Enferm Dig. 2015;107(11):659-671. doi:10.17235/reed.2015.3830/2015 9. Garrett WS. The gut microbiota and colon cancer. Science. 2019;364(6446):1133-1135. doi:10.1126/science.aaw2367 10. Wroblewski LE, Peek RM, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23(4):713-739. doi:10.1128/CMR.00011-10 11. Wu Q, Yang Z-P, Xu P, Gao L-C, Fan D-M. Association between Helicobacter pylori infection and the risk of colorectal neoplasia: a systematic review and meta-analysis. Colorectal Dis. 2013;15(7):e352-364. doi:10.1111/codi.12284 12. Yang F, Xu Y-L, Zhu R-F. Helicobacter pylori infection and the risk of colorectal carcinoma: a systematic review and meta-analysis. Minerva Med. 2019;110(5):464-470. doi:10.23736/S0026-4806.19.05942-1 13. Hang DV, Minh DT, Hoc TH, Phuoc LH, Son TQ, Le NT. H. pylori Infection and Colorectal Cancers by Anatomical Locations. Asian Pac J Cancer Prev. 2020;21(8):2431-2437. doi:10.31557/APJCP .2020.21.8.2431 14. Hu K-C, Wu M-S, Chu C-H, et al. Decreased Colorectal Adenoma Risk After Helicobacter pylori Eradication: A Retrospective Cohort Study. Clin Infect Dis. 2019;68(12):2105-2113. doi:10.1093/cid/ciy591 15. Wang D, Li Y, Zhong H, et al. Alterations in the human gut microbiome associated with Helicobacter pylori infection. FEBS Open Bio. 2019;9(9):1552-1560. doi:10.1002/2211-5463.12694 16. Dash NR, Khoder G, Nada AM, Al Bataineh MT. Exploring the impact of Helicobacter pylori on gut microbiome composition. PLoS One. 2019;14(6):e0218274. doi:10.1371/journal.pone.0218274 17. Sobhani I, Tap J, Roudot-Thoraval F, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 2011;6(1):e16393. doi:10.1371/journal.pone.0016393 18. Wang T, Cai G, Qiu Y, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012;6(2):320-329. doi:10.1038/ismej.2011.109 19. Liou J-M, Chen C-C, Chang C-M, et al. Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial. Lancet Infect Dis. 2019;19(10):1109-1120. doi:10.1016/S1473- 3099(19)30272-5
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81135-
dc.description.abstract背景介紹: 抽菸和幽門螺旋桿菌都是大腸直腸癌的危險因子。許多研究指出抽菸 會改變腸內菌相,且這些改變也發現和某些癌症的成因相關。有許多 研究指出幽門螺旋桿菌感染會改變腸內菌相。台灣的研究發現幽門螺 旋桿菌除菌治療後其大腸直腸息肉發生的機會會下降。這些現象顯示 抽菸和幽門桿菌可能皆透過改變腸內菌相而影響大腸直腸癌發生的機 會。目前並沒有任何研究探討幽門螺旋桿菌除菌和抽菸兩者對腸內菌 相的改變的交互作用及影響如何。因此本篇論文主要目的是探討幽門 螺旋桿菌除菌和抽菸對腸內菌相的交互作用及影響。 研究方法與材料: 受試者是從台大醫院幽門螺旋桿菌除菌研究中收案的病人。我們在除 菌前收集病人的糞便檢體,除菌成功後一年收集病人的糞便檢體。我 們比對了除菌前後為同一人的個案並將其分成現正抽菸組及從未抽菸 組兩組。過去抽菸但現在戒菸的受試者因為人數太少,故在此研究案 中將其排除。總共 273 個個案被收入,除菌前和除菌後的糞便檢體各 273 個,其中現正抽菸組的人數有 57 人,從未抽菸組的人數有 216 人。此外我們也針對現正抽菸組的 57 人分成幽門螺旋桿菌除菌前及 除菌後兩組(每組各 57 個)去進行分析,同時也針對從未抽菸組的 216 人分成幽門螺旋桿菌除菌前及除菌後兩組(每組各 216 個)去進行糞便 分析,我們將所有的糞便檢體送去做 16s rRNA 在 V3-V4 區的定序分 析,然後使用 R 程式來分析並比較這兩個危險因子組內及組間的腸內 菌相差異(包含 alpha 及 beta 多樣性)。 結果: 針對幽門螺旋桿菌除菌前的受試者中,現正抽菸組和從未抽菸組其腸 內菌相的 alpha 及 beta 多樣性並沒有差異,且也沒有顯著的細菌被發 現於個別的組內。針對幽門螺旋桿菌除菌後的受試者中,現正抽菸組 和從未抽菸組的腸內菌相的 alpha 及 beta 多樣性都有顯著差異,其中 現正抽菸組的Bacteroides_coprocola 這隻細菌比起從未抽菸組要來的顯 著上升,而 Bacteroides_thetaiotaomicron 這隻細菌則是在從未抽菸組比 起現正抽菸組要來的顯著上升。對於現正抽菸組而言,我們去比較幽 門螺旋桿菌除菌前後的腸內菌相,發現其腸內菌相的 alpha 及 beta 多 樣性並沒有顯著的差異。雖然如此,仍可以發現 Lactobacillales 及 Streptococcaceae 這兩隻細菌在幽門螺旋桿菌除菌前比除菌後有顯著上 升。而 Actinobacteriota 及 Blautia 這兩隻細菌則是在幽門螺旋桿菌除菌 後比除菌前有顯著上升。對於從未抽菸組而言,我們一樣去比較幽門 螺旋桿菌除菌前及除菌後的腸內菌相,發現其腸內菌相的 alpha 及 beta 多樣性都有顯著差異。進一步比較可以發現比起現正抽菸組有更多不同的細菌在幽門螺旋桿菌除菌前後的腸內菌相中有顯著差異且這些細 菌和現正抽菸組的菌相有所不同。Prevotella 這個菌相在幽門螺旋桿菌 除菌後會顯著的降低,而 Lachnospiraceae 及 Bifidobacteriaceae 的菌相則 在幽門螺旋桿菌除菌後會顯著的升高。 結論: 幽門螺旋桿菌和抽菸對腸內菌相有交互作用且會改變及影響腸內菌 相。本研究發現幽門螺旋桿菌比起抽菸對腸內菌相的影響要大。幽門 螺旋桿菌除菌治療後會降低和大腸直腸癌相關之腸內菌相。zh_TW
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Previous issue date: 2021
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dc.description.tableofcontents目 錄 誌謝……………………………………………………………………. i 中文摘要……………………………………………………………… ii 英文摘要………………………………………………………………. iv 第一章 Introduction………………………………………………….. 1 第二章 Materials and Methods……………………………………….. 4 2.1 Study population………………………………………………… 4 2.2 DNA extraction ………………………………………………… 5 2.3 PCR analysis…………………………………………………… 5 2.4 16s rRNA sequencing…………………………………………… 6 2.5 Principle component analysis …………………………………… 7 2.6 Statistical analysis ……………………………………………… 7 第三章 Results……………………………………………………….. 7 3.1 Baseline characteristic of the subjects…………………………… 7 3.2 For pre-H. pylori eradication subjects…………………………… 8 3.3 For post-H. pylori eradication subjects…………………………… 8 3.4 For current smokers……………………………………………… 10 3.5 For non-smokers…………………………………………………10 第四章 Discussion……………………………………………………..11 第五章 Conculsion……………………………………………………..13 第六章 Study limitations………………………………………………..13 第七章 Future prospects…………………………………………….. 13 第八章 Flow charts and figures………………………………….…… 14 8.1 Figure 1 Flow chart…………………………………………………………………………… 14 8.2 Figure 2 Alpha diversity in current smokers and non-smokers for pre-H.P eradication subjects… 15 8.3 Figure 3 Beta diversity between current smokers and non-smokers in pre-H.P eradication subject…15 8.4 Figure 4 Abundance barplot between current smokers and non-smokers in pre-H.P eradication subjects………………………………………………………………………………………………16 8.5 Figure 5 Alpha diversity in current smokers and non-smokers for post-H.P eradication subjects…………………………………………………………………………………………… 17 8.6 Figure 6 Beta diversity between current smokers and non-smokers in post-H.P eradication subjects………………………………………………………………………………………………17 8.7 Figure 7 Linear discriminant analysis effect size(LEfSe)and boxplot between current smokers and non-smokers in post-H.P eradication subjects……………………………………………………… 18 8.8 Figure 8 Alpha diversity in pre- and post-H.P eradication subjects for current smokers………………………………………………………………………………………… 19 8.9 Figure 9 Beta diversity between pre- and post-H.P eradication subjects for current smokers………………………………………………………………………………………… 19 8.10 Figure 10 Linear discriminant analysis effect size(LEfSe)and boxplot between pre- and post-H.P eradication subjects in current smokers…………………………………………………………… 20 8.11 Figure 11 Alpha diversity in pre- and post-H.P eradication subjects for non-smokers………………………………………………………………………………………… 21 8.12 Figure 12 Beta diversity between pre- and post-H.P eradication subjects for non-smokers………………………………………………………………………………………… 21 8.13 Figure 13 Linear discriminant analysis effect size(LEfSe) between pre- and post-H.P positive and H.P eradication subjects for non-smokers in Species and Order level……………………………… 22 8.14 Figure 14 Boxplot between pre- and post-H.P positive and H.P eradication subjects for non-smokers………………………………………………………………………………………… 22 8.15 Figure 15 Boxplot between pre- and post-H.P positive and H.P eradication subjects for non-smokers…………………………………………………………………………………………23 第九章 Table……………………………………………………….… 23 第十章 References………………………………………………….… 24
dc.language.isoen
dc.subject大腸直腸癌zh_TW
dc.subject幽門螺旋桿菌除菌治療zh_TW
dc.subject抽菸zh_TW
dc.subject腸內菌相zh_TW
dc.subjectSmokingen
dc.subjectHelicobacter pylori eradicationen
dc.subjectColorectal canceren
dc.subjectGut microbiotaen
dc.title幽門螺旋桿菌除菌治療和抽菸對腸內菌相的交互作用zh_TW
dc.titleThe interaction of smoking and Helicobacter pylori eradication on gut microbiotaen
dc.date.schoolyear109-2
dc.description.degree碩士
dc.contributor.coadvisor吳明賢(Ming-Shiang Wu)
dc.contributor.oralexamcommittee楊宏志(Hsin-Tsai Liu),(Chih-Yang Tseng)
dc.subject.keyword幽門螺旋桿菌除菌治療,抽菸,腸內菌相,大腸直腸癌,zh_TW
dc.subject.keywordHelicobacter pylori eradication,Smoking,Gut microbiota,Colorectal cancer,en
dc.relation.page25
dc.identifier.doi10.6342/NTU202102225
dc.rights.note同意授權(限校園內公開)
dc.date.accepted2021-08-19
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept臨床醫學研究所zh_TW
Appears in Collections:臨床醫學研究所

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