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研究生：	黃意婷 Huang, Yi-Ting
論文名稱：	幽門桿菌除菌治療後與胃部癌前病變消退相關的胃部微生物 Gastric microbes associated with regression of gastric precancerous lesions after Helicobacter pylori eradication
指導教授：	鄭修琦 Cheng, Hsiu-Chi
共同指導:	陳芃潔 Chen, Peng-Chieh
學位類別：	碩士 Master
系所名稱：	醫學院 - 臨床醫學研究所 Institute of Clinical Medicine
論文出版年：	2023
畢業學年度：	111
語文別：	英文
論文頁數：	111
中文關鍵詞：	幽門桿菌除菌、胃癌前病變、胃部微菌相
外文關鍵詞：	H. pylori eradication, gastric precancerous lesion, gastric microbiota
相關次數：	點閱：171 下載：0
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幽門桿菌感染會引起慢性胃炎，並增加罹患胃癌的風險。使用藥物進行幽門桿菌除菌治療或內視鏡切除再生不良病變可能使胃部癌前病變消退，但在大多數病人中，根除幽門桿菌後癌前病變仍然存在，且持續存在惡化為胃癌的可能性。慢性幽門桿菌感染導致胃酸分泌減少，改變胃中的微環境，從而引起微生物相組成的改變。因此，我們假設在幽門桿菌根除後，除幽門桿菌外的其他微生物相可能會在癌前病變的消退上扮演促進或阻擾的角色。因此，我們的研究中，將透過次世代定序的技術，對細菌16S rRNA基因高度變異區域V4進行定序，分析具有胃部癌前病變病人的胃黏膜組織上所定植菌群的組成，藉此找出與癌前病變消退相關的特定微生物。我們進行了罹患胃癌不同風險組別的微生物多樣性分析，發現α-多樣性在除菌治療後會上升，顯示清除幽門桿菌大量定植可以恢復胃部菌相中物種豐富度和均勻度，並藉由β-多樣性分析結果得知除菌治療後的菌相組成結構會與沒有幽門桿菌感染的胃部菌相接近。其中，Prevotella melaninogenica、Veillonella dispar、Capnocytophaga ochracea在沒有幽門桿菌感染的胃部菌相中相對數量顯著較多，Prevotella pallens、Haemophilus parainfluenzae在除菌治療後有癌前病變的病人胃部菌相中相對數量顯著較多，而Ruminococcus gnavus則是在除菌治療後仍屬胃癌高風險病人和胃癌病人的胃部菌相中相對數量顯著較多，因此R. gnavus為幽門桿菌除菌治療後推進胃癌進展的潛在關鍵參與者，這些發現有助於瞭解幽門桿菌感染病人即使在除菌後仍具有胃癌風險之胃微菌相組成。

Helicobacter pylori (H. pylori) infection leads to acute gastritis and may turn into chronic gastritis. As we all know, H. pylori infection related to the development of precancerous lesions, such as chronic atrophic gastritis or intestinal metaplasia, which in turn trigger the progression of gastric cancer. H. pylori eradication or endoscopic resection for dysplasia may be a reversible process for gastric precancerous lesions. However, most patients with precancerous lesions that do not reverse after eradication therapy may still have a high risk for developing gastric cancer. Chronic H. pylori infection results in decreased gastric acid secretion, which may alter gastric microenvironment to induce change in bacterial colonization. Therefore, we hypothesize that non-H. pylori microbes may induce or halt regression of precancerous lesions after H. pylori eradication. In our study, we will characterize the indicative microbes that are associated with regression of precancerous lesions through profiling gastric microbiota of patients with precancerous lesions by next-generation sequencing (NGS) of the variable region 4 (V4) of the bacterial 16S rRNA gene. We performed diversity analysis of different groups and found that α-diversity increased after eradication treatment, showing that eradicating the massive colonization of H. pylori can restore the richness and evenness of species in the stomach microbiota. And according to the results of β-diversity analysis, it was found that the composition of gastric microbiota after eradication treatment was similar to that without H. pylori infection. Among them, the relative abundance of Prevotella melaninogenica, Veillonella dispar, Capnocytophaga ochracea were significantly higher in the gastric microbiota without H. pylori infection, Prevotella pallens, Haemophilus parainfluenzae were significantly higher in the patients with gastric precancerous lesions after eradication, while the relative abundance of Ruminococcus gnavus was significantly higher in the gastric microbiota of patients with high risk of gastric cancer after eradication treatment and patients with gastric cancer. Therefore, we identified R. gnavus as a potential key player in the sequential stages of gastric cancer progression after H. pylori eradication. These findings help to reveal the gastric microbiota composition in H. pylori-infected patients who were still at risk of gastric cancer development even though H. pylori was eradicated.

Abstract	I
中文摘要	III
誌    謝	IV
Content	1
Abbreviation	5
Chapter 1 Introduction	6
1.1	H. pylori infection	7
1.2	Correa’s cascade	7
1.3	OLGA and OLGIM	8
1.4	The gastric microbiota changes with gastric cancer progression	8
1.5	Risk of gastric cancer after H. pylori eradication	9
Chapter 2 Materials and Methods	11
2.1	Study design	12
2.2	Sample collection	12
2.3	DNA extraction	12
2.4	16S rRNA gene sequencing and library preparation	13
2.5	Gastric microbiota analyses	13
2.6	Functional features analysis of gastric microbiota	14
Chapter 3 Results	15
3.1	Subject enrollment	16
3.2	Changes of the gastric microbiota composition	16
3.3	No significant differences in diversity of the gastric microbiota between the antrum and body	16
3.4	The α-diversity of the gastric microbiota was decreased by H. pylori infection and increased after H. pylori eradication	18
3.5	Differences in β-diversity between the control group and subgroups with precancerous lesions	19
3.6	Differences in β-diversity among groups with the same status before eradication	21
3.7	Differences in β-diversity between the gastric cancer group and the non-cancerous groups	22
3.8	Differential relative abundances of bacterial taxa analyzed by metastats analyses among each group at species level	23
3.9	Differential functional characteristics among each group	25
Chapter 4 Discussion	27
Chapter 5 Figures and Table	34
Table 1. Baseline demographic characteristics of participants	35
Table 1. Baseline demographic characteristics of participants	35
Table 2. PICRUSt results with statistically significant features (P < 0.05) compared between the control group and the groups of precancerous lesions before eradication  as category level 2	36
Table 2. PICRUSt results with statistically significant features (P < 0.05) compared between the control group and the subgroups with precancerous lesions before eradication as category level 2	36
Table 2. (continued)	37
Table 3. PICRUSt results with statistically significant features (P < 0.05) compared between control group and the groups of precancerous lesions before eradication as category level 3	38
Table 3. PICRUSt results with statistically significant features (P < 0.05) compared between the control group and the subgroups with precancerous lesions before eradication as category level 3	38
Table 3. (continued)	39
Table 4. PICRUSt results with statistically significant features (P < 0.05) compared between control group and the groups of precancerous lesions after eradication as category level 2	40
Table 4. PICRUSt results with statistically significant features (P < 0.05) compared between the control group and the subgroups with precancerous lesions after eradication as category level 2	40
Table 5. PICRUSt results with statistically significant features (P < 0.05) compared between control group and the groups of precancerous lesions after eradication as category level 3	41
Table 5. PICRUSt results with statistically significant features (P < 0.05) compared between the control group and the subgroups with precancerous lesions after eradication as category level 3	41
Table 5. (continued)	42
Table 5. (continued)	43
Figure 1. Study design	44
Figure 2. The gastric microbiota composition of each sample in the control group and other subgroups	50
Figure 3. The α-diversity of the antrum and body in each group	52
Figure 4. The β-diversity between the antrum and body in each group	54
Figure 5. The α-diversity before and after eradication treatment between the control group and other subgroups	56
Figure 6. The β-diversity before and after eradication treatment between the control group and other subgroups	59
Figure 7. The β-diversity before and after eradication therapy for subgroups of the same severity before eradication therapy	61
Figure 8. The β-diversity between the groups before and after eradication therapy and the gastric cancer group	63
Figure 9. Bacteria with significant differences in relative abundance at the species level between subgroups before eradication therapy	65
Figure 10. Bacteria with significant differences in relative abundance at the species level between the subgroups after eradication therapy	68
Chapter 6 References	69
Supplementary data	74
                                    

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2026-01-31公開

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