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微生物群落在胰腺癌及其癌前病变中的作用——MiBiPanc系统评价与荟萃分析的研究方案

The role of the MicroBiome in PANCreatic cancer and its precursors- the study protocol of the MiBiPanc systematic review and meta-analysis.

作者信息

Pianka My-Lan, Werba Alexander, Zimmermann Samuel, Vey Johannes A, Kalkum Eva, Tenckoff Solveig, Tony-Odigie Andrew, Michalski Christoph W, Pianka Frank

机构信息

Department of Infectious Diseases, Medical Microbiology and Hygiene, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.

Study Center of the German Society of Surgery, University of Heidelberg, Heidelberg, Germany.

出版信息

Syst Rev. 2025 Jul 18;14(1):150. doi: 10.1186/s13643-025-02910-3.

DOI:10.1186/s13643-025-02910-3
PMID:40682107
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12273363/
Abstract

BACKGROUND

Pancreatic cancer is the third leading cause of cancer-related death in Northern America and fourth in Europe. Emerging evidence suggests that the pancreatic microbiome may play a significant role in the development and progression of this disease. Although the human microbiota contributes to health by supporting nutritional and hormonal homeostasis, modulating inflammation, detoxifying harmful compounds, and producing beneficial metabolites, several studies have implicated its crucial modulatory role in numerous diseases, including cancer. The main objective of this review is to investigate the specific relationship between the microbiome and pancreatic carcinogenesis.

METHODS

A comprehensive literature search will identify studies examining the microbiome in human samples of saliva, pancreatic fluid, bile, pancreatic tissue, and feces of patients with chronic pancreatitis, precancerous pancreatic lesions, and pancreatic cancer. Studies differentiating bacteria to at least the genus level will be prioritized. Eligible studies include randomized controlled trials and observational studies analyzing the human microbiome in patients with chronic pancreatitis, pancreatic precursor lesions, or pancreatic cancer compared to healthy controls. Studies analyzing nonhuman samples, single bacterial strains, or lacking comparator groups will be excluded. The following databases will be searched without any restrictions to the publication date up until December 2024: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Embase, and Web of Science. Animal studies, case reports, and studies not reporting analyses of human samples are excluded. Details regarding blinding, risk of bias, and funding sources will be extracted and assessed. The main outcomes include the bacterial diversity in each sample type (stool, saliva, bile, intratumoral, and tissue) itemized for each diagnosis, identifying differentially abundant or depleted taxa, and evaluating the correlation of specific bacteria with disease prevention or progression and clinical outcomes. Data extraction will be performed independently by two reviewers. Risk-of-bias assessment will be performed using Cochrane tools appropriate for each study design. Comparisons will be analyzed by descriptive statistics, and meta-analyses will be performed when applicable. The review will be conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

DISCUSSION

In summary, this systematic review aims to synthesize studies analyzing microbiome profiles in patients with chronic pancreatitis, precursor lesions, and pancreatic cancer, focusing on identifying bacterial diversity and specific taxa related to disease progression and development of cancer in comparison to healthy controls and will include a thorough critical appraisal of the available literature. Anticipated limitations include heterogeneity in microbiome sampling methods and potential variability in taxonomic resolution across studies.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO CRD42023487995.

摘要

背景

胰腺癌是北美地区癌症相关死亡的第三大主要原因,在欧洲则是第四大原因。新出现的证据表明,胰腺微生物群可能在这种疾病的发生和发展中发挥重要作用。尽管人类微生物群通过维持营养和激素稳态、调节炎症、解毒有害化合物以及产生有益代谢产物来促进健康,但多项研究表明其在包括癌症在内的多种疾病中具有关键的调节作用。本综述的主要目的是研究微生物群与胰腺癌发生之间的具体关系。

方法

全面的文献检索将确定研究慢性胰腺炎、癌前胰腺病变和胰腺癌患者的唾液、胰液、胆汁、胰腺组织和粪便等人体样本中微生物群的研究。将优先考虑至少区分到属水平的细菌研究。符合条件的研究包括随机对照试验和观察性研究,分析慢性胰腺炎、胰腺前驱病变或胰腺癌患者与健康对照相比的人类微生物群。分析非人类样本、单一细菌菌株或缺乏比较组的研究将被排除。将检索以下数据库,对截至2024年12月的出版日期没有任何限制:Cochrane对照试验中心注册库(CENTRAL)、医学期刊数据库(通过PubMed)、Embase和科学引文索引。动物研究、病例报告以及未报告人类样本分析的研究均被排除。将提取并评估有关盲法、偏倚风险和资金来源的详细信息。主要结果包括每种诊断下各样本类型(粪便、唾液、胆汁、肿瘤内和组织)的细菌多样性,识别差异丰富或减少的分类群,并评估特定细菌与疾病预防或进展及临床结果的相关性。数据提取将由两名审阅者独立进行。将使用适合每种研究设计的Cochrane工具进行偏倚风险评估。比较将通过描述性统计进行分析,适当时将进行荟萃分析。本综述将按照系统评价和荟萃分析的首选报告项目(PRISMA)指南进行。

讨论

总之,本系统评价旨在综合分析慢性胰腺炎、前驱病变和胰腺癌患者微生物群谱的研究,重点是与健康对照相比,识别与疾病进展和癌症发生相关的细菌多样性和特定分类群,并将对现有文献进行全面的批判性评价。预期的局限性包括微生物群采样方法的异质性以及各研究中分类分辨率的潜在变异性。

系统评价注册

PROSPERO CRD42023487995。

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Alterations of the bile microbiome is associated with progression-free survival in pancreatic ductal adenocarcinoma patients.胆汁微生物组的改变与胰腺导管腺癌患者的无进展生存期相关。
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