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‘Helicobacter’ is not the sole microorganism responsible for various gastric diseases evidenced by human gastric microbiota transplantation in germ-free mice |
Helicobacter pylori is a significant factor related with the development of gastric cancer (GC) in human. Mouse-adapted Helicobacter-infected or insulin-gastrin mice are widely used as gastric disease animal models.Kwon et al. showed that gastric microbiota transplant (GMT) from human patients with intestinal metaplasia or GC into germ-free (GF) mice induced parietal cell loss, metaplasia development and expansion of the proliferating epithelial zone. Also, it is evidenced human microbiota selectively colonised mouse recipients and appeared to contribute to the development of features characteristic of premalignant GC lesions. Interestingly, in long-term follow-up of mice after GMT, further premalignant changes with dysplasia were observed in the mouse stomach. These results suggest that GF mice are useful tool for analysing the causality of associations reported in human gastric microbiome studies.
Histopathological analysis of recipient germ-free (GF) mouse stomachs transplanted with human endoscopic biopsied tissues |
[Reference] Soon-Kyeong Kwon, Jun Chul Park, Kwang H Kim, Jaekyung Yoon, Yejin Cho, Buhyun Lee, Jin-Jae Lee, Haengdueng Jeong4, Yeseul Oh, Sung-Hee Kim, So Dam Lee, Bo Ram Hwang, Yusook Chung , Jihyun F Kim, Ki Taek Nam, Yong Chan Lee. Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice. Gut. 2021 Aug 13;gutjnl-2021-324489. doi: 10.1136/gutjnl-2021-324489. Online ahead of print.
[Main Author] Correspondence to Professor Jihyun F Kim, Department of Systems Biology and Division of Life Sciences, Yonsei University, Seoul, Republic of Korea; jfk1@yonsei.ac.kr; Professor Ki Taek Nam, Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; kitaek@yuhs.ac; Professor Yong Chan Lee, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; leeyc@yuhs.ac
Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice |
Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. Korean researchers at Yonsei and Gyeongsang National University report that gastric microbiota transplant (GMT) from human patients with intestinal metaplasia or GC into germ-free (GF) mice induced premalignant changes with dysplasia in the mouse stomach. They concluded that human microbiota selectively colonised mouse recipients and appeared to contribute to the development of features characteristic of premalignant GC lesions. The study appeared in the journal Gut (2020 JCR IF = 23.059) in August, 2021.
The researchers aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. They found that the microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Interestingly, marked dysplastic changes were noted in the GF mouse at 1 year post inoculation.
Prof. Kwon said that "We showed for the first time that the gastric microbiota transplant (GMT) from human patients with intestinal metaplasia or GC into germ-free (GF) mice induced significant premalinant changes in the mouse stomach mimicking human gastric diseases." "Our results suggested that microbial members other than H. pylori may trigger features associated with human gastirc cancer. It is strongly suggested that transplanting human gastric microbiota into GF mice is a novel animal model for studying human gastric diseases including gastric cancer.“, Prof. Lee commented.
[Reference] Kwon S-K et al. (2021) “Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice.” Gut
[Main Author] Correspondence to Professor Jihyun F Kim, Department of Systems Biology and Division of Life Sciences, Yonsei University, Seoul, Republic of Korea; jfk1@yonsei.ac.kr; Professor Ki Taek Nam, Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; kitaek@yuhs.ac; Professor Yong Chan Lee, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; leeyc@yuhs.ac |