幽门螺杆菌 CagA 通过增加胆囊上皮细胞的渗透性促进胆结石的形成

IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Helicobacter Pub Date : 2024-06-14 DOI:10.1111/hel.13100
Jingjing Yu, Yuanhang He, Wenchao Yao, Tianming Liu, Xuxu Liu, Yi Zheng, Chenjun Hao, Dongbo Xue
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引用次数: 0

摘要

背景:胆结石的形成往往伴随着慢性炎症,而炎症和结石形成的机制尚未完全明了。我们的目的是利用单细胞转录组学、大容量转录组学和微生物组数据来探索可能导致慢性炎症和胆结石形成的关键致病菌及其相关机制。方法:从基因表达总库(GEO)数据库中提取胆结石小鼠模型的scRNA-seq数据,并使用FindCluster()软件包进行细胞聚类分析。还从 GEO 数据库中提取了胆石症患者的大量转录组学数据,并使用 GO 和 KEGG 富集分析评估了组间功能差异。此外,还对无症状胆结石患者胆囊粘膜样本(n = 6)和肝移植供体胆囊粘膜样本(n = 6)进行了 16S rRNA 测序,以确定与结石形成和慢性炎症相关的关键细菌。通过构建动物模型来研究这些关键致病菌属促进胆结石形成的机制:结果:对胆结石小鼠模型(GSE179524)的 scRNA-seq 数据分析发现了七个不同的细胞群,胆结石组的中性粒细胞数量显著增加。对胆结石患者(GSE202479)的大量转录组学数据进行分析后发现,胆囊中存在慢性炎症,这可能与胆囊微生物群的菌群失调有关。16S rRNA 测序确定幽门螺旋杆菌是与胆囊慢性炎症和结石形成相关的关键细菌:结论:胆囊粘膜微生物群的菌群失调与胆石症有关,并导致慢性炎症。本研究发现幽门螺杆菌是导致胆结石形成的潜在关键黏膜常驻菌,并发现了其关键致病因子 CagA,该因子可导致胆囊黏膜屏障受损。这些发现为胆结石的预防和治疗提供了重要线索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Helicobacter pylori CagA Promotes the Formation of Gallstones by Increasing the Permeability of Gallbladder Epithelial Cells

Background

The formation of gallstones is often accompanied by chronic inflammation, and the mechanisms underlying inflammation and stone formation are not fully understood. Our aim is to utilize single-cell transcriptomics, bulk transcriptomics, and microbiome data to explore key pathogenic bacteria that may contribute to chronic inflammation and gallstone formation, as well as their associated mechanisms.

Methods

scRNA-seq data from a gallstone mouse model were extracted from the Gene Expression Omnibus (GEO) database and analyzed using the FindCluster() package for cell clustering analysis. Bulk transcriptomics data from patients with gallstone were also extracted from the GEO database, and intergroup functional differences were assessed using GO and KEGG enrichment analysis. Additionally, 16S rRNA sequencing was performed on gallbladder mucosal samples from asymptomatic patients with gallstone (n = 6) and liver transplant donor gallbladder mucosal samples (n = 6) to identify key bacteria associated with stone formation and chronic inflammation. Animal models were constructed to investigate the mechanisms by which these key pathogenic bacterial genera promote gallstone formation.

Results

Analysis of scRNA-seq data from the gallstone mouse model (GSE179524) revealed seven distinct cell clusters, with a significant increase in neutrophil numbers in the gallstone group. Analysis of bulk transcriptomics data from patients with gallstone (GSE202479) identified chronic inflammation in the gallbladder, potentially associated with dysbiosis of the gallbladder microbiota. 16S rRNA sequencing identified Helicobacter pylori as a key bacterium associated with gallbladder chronic inflammation and stone formation.

Conclusions

Dysbiosis of the gallbladder mucosal microbiota is implicated in gallstone disease and leads to chronic inflammation. This study identified H. pylori as a potential key mucosal resident bacterium contributing to gallstone formation and discovered its key pathogenic factor CagA, which causes damage to the gallbladder mucosal barrier. These findings provide important clues for the prevention and treatment of gallstones.

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来源期刊
Helicobacter
Helicobacter 医学-微生物学
CiteScore
8.40
自引率
9.10%
发文量
76
审稿时长
2 months
期刊介绍: Helicobacter is edited by Professor David Y Graham. The editorial and peer review process is an independent process. Whenever there is a conflict of interest, the editor and editorial board will declare their interests and affiliations. Helicobacter recognises the critical role that has been established for Helicobacter pylori in peptic ulcer, gastric adenocarcinoma, and primary gastric lymphoma. As new helicobacter species are now regularly being discovered, Helicobacter covers the entire range of helicobacter research, increasing communication among the fields of gastroenterology; microbiology; vaccine development; laboratory animal science.
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