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Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice

 Soon-Kyeong Kwon  ;  Jun Chul Park  ;  Kwang H Kim  ;  Jaekyung Yoon  ;  Yejin Cho  ;  Buhyun Lee  ;  Jin-Jae Lee  ;  Haengdueng Jeong  ;  Yeseul Oh  ;  Sung-Hee Kim  ;  So Dam Lee  ;  Bo Ram Hwang  ;  Yusook Chung  ;  Jihyun F Kim  ;  Ki Taek Nam  ;  Yong Chan Lee 
 GUT, Vol.71(07) : 1266-1276, 2022-07 
Journal Title
Issue Date
Animals ; Gastric Mucosa / metabolism ; Helicobacter Infections* / pathology ; Helicobacter pylori* ; Humans ; Hyperplasia / pathology ; Metaplasia / pathology ; Mice ; Mice, Inbred C57BL ; Microbiota* ; Stomach Neoplasms* / pathology
dysplasia ; gastric cancer ; intestinal microbiology ; pre-malignancy
Objective: 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. We 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.

Design: Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year.

Results: 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. Marked dysplastic changes were noted at 1 year post inoculation.

Conclusion: Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kwang Hui(김광휘)
Kim, Sung-Hee(김성희)
Nam, Ki Taek(남기택)
Park, Jun Chul(박준철) ORCID logo https://orcid.org/0000-0001-8018-0010
Lee, Yong Chan(이용찬) ORCID logo https://orcid.org/0000-0001-8800-6906
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