Helicobacter pylori Pathogenic Factors and Their Interactions With the Gastric Microbiome

IF 4.3 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter Pub Date : 2025-09-21 DOI:10.1111/hel.70072

Camilia Metadea Aji Savitri, Takashi Matsumoto, Kartika Afrida Fauzia, Ricky Indra Alfaray, Langgeng Agung Waskito, Yudith Annisa Ayu Rezkitha, Tomohisa Uchida, Muhammad Miftahussurur, Yoshio Yamaoka

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Abstract

Background

Variations in Helicobacter pylori infection rates and pathogenicity do not explain the global gastric cancer incidence, indicating that other bacteria may play a role. We investigated the pathogenic factors of H. pylori and their interactions with the gastric microbiome in a population with low gastric cancer but high gastritis rates in Indonesia.

Methods

The study included 66 H. pylori-positive gastric biopsies. DNA was extracted from the bacterial cultures to examine the pathogenic factors of H. pylori. The 16S rRNA V3–V4 region was sequenced using next-generation sequencing. The microbiome analysis concentrated on α-diversity and β-diversity, along with absolute and relative abundances. Correlation analysis and predicted functional inference were conducted using SECOM and PICRUSt2.

Results

Helicobacter predominates in H. pylori-infected stomachs, limiting other bacteria. Although α-diversity was non-significant, virulent H. pylori genotypes showed greater microbial diversity, suggesting co-colonization by other taxa. Some taxa were notably abundant across pathogenic subtypes (p < 0.05), such as Veillonella sp. in East Asian-type CagA H. pylori and Klebsiella without babB. The β-diversity results indicated that microbial diversity and abundance varied according to polymorphisms in patients with different H. pylori CagA types, sabA status, homA/B, and iceA subtypes (PERMANOVA test; p < 0.05). H. pylori dominance remains unchanged when atrophy worsens, alongside decreased microbial diversity (p < 0.05 for atrophy stage 0 vs. stages 1 and 2). Microbial correlation analysis revealed that Helicobacter only had a positive linear relationship with Veillonella (SECOM(Pearson2) = 0.51, SECOM(Distance) = 0.60), whereas Streptococcus sp. correlated with several gastric taxa. Predicted functional inference showed several pathways to be depleted when atrophy progresses.

Conclusion

Various pathogenic factors impact microbial diversity, and bacteria cohabiting in the gastric environment might shape disease outcomes. Additionally, our study uncovers relationships among genera present in the stomach. More research is needed to explore how non-Helicobacter species induce or possibly safeguard against gastric pathologies.

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幽门螺杆菌致病因素及其与胃微生物群的相互作用

背景幽门螺杆菌感染率和致病性的差异并不能解释全球胃癌发病率的变化，表明可能有其他细菌在其中起作用。我们研究了幽门螺杆菌的致病因素及其与胃微生物群的相互作用，研究对象是印度尼西亚一个胃癌发病率低但胃炎发病率高的人群。方法选取66例幽门螺旋杆菌阳性胃活检。从细菌培养物中提取DNA以检测幽门螺杆菌的致病因素。采用新一代测序技术对16S rRNA V3-V4区进行测序。微生物组主要分析α-多样性和β-多样性，以及绝对丰度和相对丰度。使用SECOM和PICRUSt2进行相关性分析和预测功能推断。结果幽门螺旋杆菌感染胃中以幽门螺旋杆菌为主，限制了其他细菌。尽管α-多样性不显著，但毒性幽门螺杆菌基因型显示出更大的微生物多样性，表明有其他分类群的共定殖。一些类群在不同致病亚型中数量显著丰富（p < 0.05），如东亚型CagA中的Veillonella sp. H. pylori和无babB的Klebsiella。β-多样性结果表明，不同幽门螺杆菌CagA型、sabA状态、homA/B和iceA亚型患者的微生物多样性和丰度根据多态性而变化（PERMANOVA检验；p < 0.05）。当萎缩恶化时，幽门螺杆菌优势保持不变，同时微生物多样性减少（萎缩0期与1期和2期相比p <； 0.05）。微生物相关性分析显示，幽门螺杆菌仅与细微杆菌呈线性正相关(SECOM(Pearson2) = 0.51， SECOM(Distance) = 0.60)，而链球菌与胃内多个分类群呈线性正相关。预测的功能推断显示，当萎缩进展时，几个通路被耗尽。结论多种致病因素影响微生物多样性，细菌在胃环境中的同居可能影响疾病的预后。此外，我们的研究揭示了胃中存在的属之间的关系。需要更多的研究来探索非幽门螺杆菌物种如何诱导或可能保护胃部病变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Helicobacter 医学-微生物学

CiteScore

8.40

自引率

9.10%

发文量

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.