TY - JOUR T1 - Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice JF - Gut JO - Gut SP - 1266 LP - 1276 DO - 10.1136/gutjnl-2021-324489 VL - 71 IS - 7 AU - Soon-Kyeong Kwon AU - Jun Chul Park AU - Kwang H Kim AU - Jaekyung Yoon AU - Yejin Cho AU - Buhyun Lee AU - Jin-Jae Lee AU - Haengdueng Jeong AU - Yeseul Oh AU - Sung-Hee Kim AU - So Dam Lee AU - Bo Ram Hwang AU - Yusook Chung AU - Jihyun F Kim AU - Ki Taek Nam AU - Yong Chan Lee Y1 - 2022/07/01 UR - http://gut.bmj.com/content/71/7/1266.abstract N2 - 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.Data are available in a public, open access repository. ER -