Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besidesHelicobacter pylorimay 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. 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. 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. 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.
|Publication status||Published - 2021 Aug 13|
Bibliographical noteFunding Information:
Funding This study was supported in part by grants from the National Research Foundation of Korea (grant nos. NRF-2017R1A2B201288714 and NRF-2017M3A9F304772821) and the Korea Health Technology R&D Project (HI17C1516010018) through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea to YCL; the Korea Mouse Phenotyping Project (NRF-2016M3A9D5A01952416) and National Research Foundation of Korea (NRF-2017M3A9F3041234) to KTN; the National Research Foundation of Korea (NRF-2014M3C9A3068822 and NRF-2017M3A9F3047857) to JFK; the National Research Foundation of Korea (NRF-2020R1C1C1004778) to S-KK; and a Faculty Research Grant of Yonsei University College of Medicine (6-2016-0059) to JCP. Publication was supported in part by the Brain Korea 21 program; JKY and YC are fellowship awardees of this program.
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