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胃微生物组的生态失调变化及其在胃癌发生中的功能意义。

Dysbiotic change in gastric microbiome and its functional implication in gastric carcinogenesis.

机构信息

Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul, 06973, Republic of Korea.

MD Healthcare R&D Institute, World Cup Buk-ro 56-gil, Mapo-gu, Seoul, Republic of Korea.

出版信息

Sci Rep. 2022 Mar 11;12(1):4285. doi: 10.1038/s41598-022-08288-9.

Abstract

Although there is a growing interest in the role of gastric microbiome on the development of gastric cancer, the exact mechanism is largely unknown. We aimed to investigate the changes of gastric microbiome during gastric carcinogenesis, and to predict the functional potentials of the microbiome involved in the cancer development. The gastric microbiome was analyzed using gastric juice samples from 88 prospectively enrolled patients, who were classified into gastritis, gastric adenoma, or early/advanced gastric cancer group. Differences in microbial diversity and composition were analyzed with 16S rRNA gene profiling, using next-generation sequencing method. Metagenomic biomarkers were selected using logistic regression models, based on relative abundances at genus level. We used Tax4Fun to predict possible functional pathways of gastric microbiome involved in the carcinogenesis. The microbial diversity continuously decreased in its sequential process of gastric carcinogenesis, from gastritis to gastric cancer. The microbial composition was significantly different among the four groups of each disease status, as well as between the cancer group and non-cancer group. Gastritis group was differently enriched with genera Akkermansia and Lachnospiraceae NK4A136 Group, whereas the cancer group was enriched with Lactobacillus and Veillonella. Predictive analysis of the functional capacity of the microbiome suggested enrichment or depletion of several functional pathways related to carcinogenesis in the cancer group. There are significant changes in the diversity and composition of gastric microbiome during the gastric carcinogenesis process. Gastric cancer was characterized with microbial dysbiosis, along with functional changes potentially favoring carcinogenesis.

摘要

尽管人们对胃微生物组在胃癌发展中的作用越来越感兴趣,但确切的机制在很大程度上尚不清楚。我们旨在研究胃微生物组在胃癌发生过程中的变化,并预测涉及癌症发展的微生物组的功能潜力。使用前瞻性纳入的 88 名患者的胃液样本分析胃微生物组,这些患者被分为胃炎、胃腺瘤或早期/晚期胃癌组。使用下一代测序方法的 16S rRNA 基因谱分析微生物多样性和组成的差异。基于属水平的相对丰度,使用逻辑回归模型选择宏基因组生物标志物。我们使用 Tax4Fun 预测胃微生物组在癌变过程中可能涉及的功能途径。从胃炎到胃癌,胃微生物组的多样性在连续发生癌变的过程中不断降低。在四个疾病状态的每组之间,以及在癌症组和非癌症组之间,微生物组成存在显著差异。胃炎组中阿克曼菌和lachnospiraceae NK4A136 组的丰度明显增加,而癌症组中乳杆菌和韦荣球菌的丰度增加。对微生物组功能能力的预测分析表明,癌症组中与癌变相关的几个功能途径存在富集或耗竭。在胃癌发生过程中,胃微生物组的多样性和组成发生了显著变化。胃癌的特征是微生物失调,同时功能发生变化,可能有利于癌变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa88/8917121/0a587277477f/41598_2022_8288_Fig1_HTML.jpg

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