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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 孟子青 | zh_TW |
| dc.contributor.advisor | Tzu-Ching Meng | en |
| dc.contributor.author | 陳常善 | zh_TW |
| dc.contributor.author | Chang-Shan Chen | en |
| dc.date.accessioned | 2023-10-03T16:41:30Z | - |
| dc.date.available | 2023-11-09 | - |
| dc.date.copyright | 2023-10-03 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-08-11 | - |
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Sulfation of arabinogalactan proteins confers privileged nutrient status to bacteroides plebeius. mBio, (2021). Kearney SM, Gibbons SM, Erdman SE, Alm EJ. Orthogonal dietary niche enables reversible engraftment of a gut bacterial commensal. Cell Rep 24, 1842-1851 (2018). | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90573 | - |
| dc.description.abstract | 腸道微生物在個體健康中扮演重要角色，包括能量代謝和免疫反應等功能。過去的臨床研究發現，大腸直腸癌患者的菌相出現特殊的組成，且近期研究也釐清部分菌種促進腫瘤生成的機制。然而，大腸直腸癌患者手術後腸道菌相的動態變化與組成仍不清楚。因此，本研究募集101名無癌症民眾以及134名大腸直腸癌患者的腸道菌相數據，建立本族群中非癌症對照組和大腸直腸癌患者的微生物差異標的。本研究同時持續追蹤收集患者手術後兩年間的菌相與生活飲食數據。結果顯示，腸道菌相的多樣性在手術後顯著下降，並在術後一年才趨向穩定。此外，我們觀察到發生排便異常和感覺神經異常的患者與其他患者的腸道菌相存在差異。並進一步以本族群的微生物差異，探討手術後腸道菌相的重建趨勢。相較於非癌症對照組，大腸直腸癌患者整體而言在手術後一年時，潛在優勢菌屬總量依舊低落，而潛在風險菌屬總量依舊較高。然而，進一步分析顯示，菌相組成較佳的患者攝取全麥食物和水果的頻率較高，而菌相組成較差的患者則更頻繁地攝取咖啡。整體而言，本研究以追蹤收案的研究方式呈現了手術治療對大腸直腸癌患者腸道菌相組成的長期影響，並分析治療間常見的後遺症與菌相之間潛在的關聯。最終，本研究發現了生活飲食習慣的選擇與菌相重建間存在重要的關聯性。 | zh_TW |
| dc.description.abstract | Gut microbiota plays crucial roles in health by regulating the energy metabolism and immune responses. A distinct gut microbiota composition is observed in patients with colorectal cancer (CRC), and some bacteria promotes its tumor development. However, the dynamic changes and regulation mechanisms of gut microbiota post-surgery in patients with CRC remain unclear. Therefore, in this study, we investigated the changes in the microbiota of 134 patients with CRC before and two years after surgery. The results revealed a significant decrease in the gut microbiota diversity after surgery, which tended to stabilize one-year post-surgery. Compared to other patients, differences in gut microbiota were observed in patients with abnormal bowel movements and sensory nerve abnormalities. Additionally, we identified several microbes at the genus level that were enriched in non-cancer controls and patients with CRC. We investigated the trends in gut microbiota reconstruction after surgery using these markers. Overall, compared to the non-cancer control group, patients with CRC exhibited high levels of CRC-enriched genera one-year post-surgery, whereas the levels of control-enriched genera remained low. Further analysis indicated that patients with a favorable gut microbiota composition exhibited a high frequency of whole grain food and fruit consumption, whereas those with an unfavorable composition exhibited a high frequency of coffee intake. In conclusion, this follow-up study demonstrated the long-term impact of surgical treatment on the gut microbiota composition of patients with CRC and elucidated the dietary effects on the restructuring of gut microbiota after surgery. | en |
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| dc.description.provenance | Made available in DSpace on 2023-10-03T16:41:30Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | Table of Contents
謝辭I 中文摘要 II Abstract III List of Abbreviations IV Chapter 1: Literature review 1 1.1 Epidemiology and Carcinogenesis of CRC 1 1.2 Development of CRC 5 1.3 Current available therapies for colon and rectal cancer 8 1.4 The role of gut microbiota in health and disease 10 1.5 The role of dietary nutrients in the gut microbiota 13 1.6 Gut microbiota in CRC development 15 1.7 Effect of Colorectal Cancer treatment on gut microbiota 17 1.8 Aim of the study 18 Chapter 2: Microbiota profiles of patients with CRC and non-cancer controls 20 2.1 Introduction 20 2.2 Materials and methods 21 2.2.1 Subject enrollment and study design 21 2.2.2 Human fecal sample collection 23 2.2.3 Genomic extraction and sequencing of human fecal samples 23 2.2.4 Sequencing data processing and statistical analysis 24 2.3 Results 26 2.3.1 Distinct fecal microbiome profiles in patients with colorectal cancer compared to non-cancer controls 26 2.3.2 Faecal microbial biomarkers in patients with CRC 28 2.4 Discussion 35 2.5 Summary 40 Chapter 3: The impact of surgery on the long-term disruption of gut microbiota 41 3.1 Introduction 41 3.2 Materials and methods 42 3.2.1 Sample enrollment and study design 42 3.2.2 Fecal sample collection and genomic sequencing 44 3.2.3 Processing of sequencing data and statistical analysis 44 3.3 Results 45 3.3.1 Post-surgical restructuring of the gut microbiota in patients with CRC 45 3.3.2 Gut microbiota profiles of patients with CRC one year after surgery 49 3.3.3 Correlations between known sequelae and post-treatment gut microbial profiles in patients with CRC 52 3.4 Discussion 56 3.5 Summary 64 Chapter 4: Dietary effects on the post-surgery restructuring of gut microbiota in patients with CRC 65 4.1 Introduction 65 4.2 Materials and methods 66 4.2.1 Subject enrollment and study design 66 4.2.2 Fecal sample collection and genomic sequencing 66 4.2.3 Processing of sequencing data and questionnaires and statistical analysis 66 4.3 Results 67 4.3.1 Profiles of control- and CRC-enriched microbial compositions in patients before and after surgery 67 4.3.2: Effects of postoperative dietary habits on the restructuring of gut microbiota in patients with CRC 70 4.4 Discussion 78 4.5 Conclusion 91 Chapter 5: Summary and Future Studies 93 References 94 Appendix-1 Questionnaire 106 List of Figures Figure 1. Global distribution of CRC incidence and mortality rates 11. 3 Figure 2. World CRC incidence and mortality rates in 2020 by income level, gender, and age groups 11. 4 Figure 3. Representation of the prevalent genetic mutations in the course of CRC advancement and the cellular mechanisms that are triggered 28. 7 Figure 4. Progression of colorectal cancer, its stages, and the principal genetic alterations across the continuum of tumor development 4. 7 Figure 5. Colon cancer surveillance process 29. 9 Figure 6. Human microbiota dysbiosis into various diseases 52. 12 Figure 7. The development of CRC is influenced by gut microbial dysbiosis, which occurs through a variety of molecular mechanisms 75. 16 Figure 8. Flow chart of patient enrollment in this chapter. 22 Figure 9. The workflow of 16S rRNA gene sequencing data processing and analysis97. 25 Figure 10. Fecal microbiome distribution in patients with CRC. 27 Figure 11. Cladogram obtained from Linear Discriminant Analysis (LDA) effect size (LEfSe) analysis showing characteristics of taxonomic signatures in patients with CRC. 31 Figure 12. Relative abundance of the control- and CRC-enriched genera. 32 Figure 13. Predictive performance in patients with CRC using receiver opera ROC analysis with different data. 34 Figure 14. Gut microbiota with clinical data target selection. 39 Figure 15. Follow-up process of data collection. 43 Figure 16. Fecal microbiome diversity in patients undergoing treatment. 46 Figure 17. Fecal microbiome distribution in patients undergoing treatment. 47 Figure 18. The Firmicutes/Bacteroidetes Ratio in patients undergoing treatment. 48 Figure 19. Cladogram obtained from LEfSe analysis showing the characteristics of taxonomic signatures in 12 months post-surgery patients with CRC. 50 Figure 20. Significantly enriched bacterial taxa from controls, patients before surgery, and the one-year post-surgery group. 51 Figure 21. Cladogram from LEfSe analysis revealing taxonomic signatures in patients with bowel dysfunction. 53 Figure 22. Relative abundance of characteristic genera and species in patients with bowel dysfunction. 54 Figure 23. Cladogram obtained from LEfSe analysis showing the characteristics of taxonomic signatures in patients with paresthesia. 56 Figure 24. Colonoscopy did not exert any significant impact on gut microbial diversity. 58 Figure 25. Impact of colonoscopy on gut microbial communities. 59 Figure 26. Effect of surgical antibiotic prophylaxis on gut microbiome diversity. 60 Figure 27. Impact of short-term dietary changes on gut microbiome. 61 Figure 28. Impact of chemotherapy on gut microbiome restructuring in post-surgery patients with CRC. 62 Figure 29. Microbial biomarkers at 12 months post-surgery. 68 Figure 30. Development trends of microbial biomarkers 12 months post-surgery. 69 Figure 31. Principal component analysis (PCA) illustrating the relationship between one-year post-surgery gut microbiota composition and lifestyle and dietary habits of patients with CRC one-year post-surgery (n = 134). 72 Figure 32. Classification of gut microbiota composition as good or bad one year after surgery. 74 Figure 33. Principal component analysis (PCA) illustrates the grouping effect based on the composition of gut microbiota targeting control-enriched genera (ConR) and CRC-enriched genera (CRCR) in one-year post-surgery patients with CRC. 82 Figure 34. Principal component analysis (PCA) illustrated the relationship between the changes in gut microbiota composition of CRC patients one year after surgery and their lifestyle and dietary habits (n = 130). 83 Figure 35. Clinical characterization of B. plebeius in non-cancer control, patients before surgery, and 12 months post-surgery. 85 Figure 36. Development trends of microbial biomarkers in patients with recurrence or metastasis. 88 Figure 37. Development trends of microbial biomarkers in patients who died. 90 List of Tables Table 1. Information on the study participants. 23 Table 2. List of control- and CRC-enriched genera. 33 Table 3. Comparison of control-enriched and CRC-enriched genera and their associations from existing studies. 36 Table 4. Odds ratios and 95% confidence intervals (CIs) present the differences in lifestyle and dietary habit questionnaire items between two microbiota composition groups. 75 Table 5. Negative relative risk reduction (RRR) presenting the differences in lifestyle and dietary habit questionnaire items between two microbiota composition groups. 76 Table 6. Positive relative risk reduction (RRR) presents the differences in lifestyle and dietary habit questionnaire items between two microbiota composition groups. 77 Table 7. Odds ratios and relative risk reduction (RRR) presenting the correlation in milk and sugar intake between two microbiota composition groups. 80 Table 8. Patient outcomes in the project and study cohort. 87 Table 9. Microbiota grouping and related information in patients with metastasis or recurrence. 87 Table 10. Microbiota grouping and related information in patients passed away. 89 | - |
| dc.language.iso | en | - |
| dc.title | 探討手術治療對大腸直腸癌患者腸道菌相的干擾以及飲食與營養對患者術後腸道菌相重建的影響 | zh_TW |
| dc.title | Evaluation of surgical impact on the long-term disruption of gut microbiota and dietary effects on the post-surgery restructuring of gut microbiota in patients with colorectal cancer | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 陳明汝;潘文涵;魏柏立;楊欣洲 | zh_TW |
| dc.contributor.oralexamcommittee | Ming-Ju Chen;Wen-Harn Pan;Po-Li Wei;Hsin-Chou Yang | en |
| dc.subject.keyword | 大腸直腸癌,腸道微生物相,臨床追蹤研究,手術治療,16S rRNA基因,營養攝取,菌群失調, | zh_TW |
| dc.subject.keyword | colorectal cancer,gut microbiota,clinical follow-up study,post-surgery,16S rRNA gene,dietary,dysbiosis, | en |
| dc.relation.page | 110 | - |
| dc.identifier.doi | 10.6342/NTU202303283 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-08-11 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科學研究所 | - |
| 顯示於系所單位： | 生化科學研究所 | |
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