Savitri Camilia Metadea Aji, Matsumoto Takashi, Fauzia Kartika Afrida, Alfaray Ricky Indra, Waskito Langgeng Agung, Rezkitha Yudith Annisa Ayu, Uchida Tomohisa, Miftahussurur Muhammad, Yamaoka Yoshio
Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Oita, Japan.
Helicobacter Pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
Helicobacter. 2025 Sep-Oct;30(5):e70072. doi: 10.1111/hel.70072.
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.
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.
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.
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.
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，这表明其他细菌可能也起到了一定作用。我们在印度尼西亚胃癌发病率低但胃炎发病率高的人群中，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。
该研究纳入了66例幽门螺杆菌阳性的胃活检样本。从细菌培养物中提取DNA，以检测幽门螺杆菌的致病因素。使用二代测序对16S rRNA V3-V4区域进行测序。微生物群分析集中在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。
在幽门螺杆菌感染的胃中，幽门螺杆菌占主导地位，限制了其他细菌。虽然α多样性无显著差异，但有毒力的幽门螺杆菌基因型显示出更大的微生物多样性，提示存在其他分类群的共同定植。一些分类群在不同致病亚型中显著丰富（p<0.05），如东亚型CagA幽门螺杆菌中的韦荣球菌属和无babB的克雷伯菌属。β多样性结果表明，不同幽门螺杆菌CagA类型、sabA状态、homA/B和iceA亚型患者的微生物多样性和丰度因多态性而异（PERMANOVA检验；p<0.05）。当萎缩加重时，幽门螺杆菌的优势地位保持不变，同时微生物多样性降低（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，幽门螺杆菌仅与韦荣球菌有正线性关系（SECOM（Pearson2）=0.51，SECOM（距离）=0.60），而链球菌属与几种胃内分类群相关。预测功能推断显示，当萎缩进展时，有几种途径会减少。
多种致病因素影响微生物多样性，共存于胃环境中的细菌可能会影响疾病结局。此外，我们的研究揭示了胃中存在的属之间的关系。需要更多研究来探索非幽门螺杆菌物种如何诱发或预防胃部病变。
