Long-term persistence of gastric dysbiosis after eradication of Helicobacter pylori in patients who underwent endoscopic

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ORIGINAL ARTICLE

Long‑term persistence of gastric dysbiosis after eradication of Helicobacter pylori in patients who underwent endoscopic submucosal dissection for early gastric cancer Toshio Watanabe1   · Yuji Nadatani1 · Wataru Suda2 · Akira Higashimori1 · Koji Otani1 · Shusei Fukunaga1 · Shuhei Hosomi1 · Fumio Tanaka1 · Yasuaki Nagami1 · Koichi Taira1 · Tetsuya Tanigawa1,3 · Geicho Nakatsu4 · Masahira Hattori2,5 · Yasuhiro Fujiwara1 Received: 20 August 2020 / Accepted: 31 October 2020 © The Author(s) 2020

Abstract Background  Gastric microbiome, other than Helicobacter pylori, plays a role in the tumorigenesis of gastric cancer (GC). Patients who undergo endoscopic submucosal dissection for early GC have a high risk of developing metachronous GC even after successful eradication of H. pylori. Thus, we investigated the microbial profiles and associated changes in such patients after the eradication of H. pylori. Methods  A total of 19 H. pylori-infected patients with early GC who were or to be treated by endoscopic resection, with paired biopsy samples at pre- and post-eradication therapy, were retrospectively enrolled. Ten H. pylori-negative patients were enrolled as controls. Biopsy samples were analyzed using 16S rRNA sequencing. Results  H. pylori-positive patients exhibited low richness and evenness of bacteria with the deletion of several genera, including Blautia, Ralstonia, Faecalibacterium, Methylobacterium, and Megamonas. H. pylori eradication partially restored microbial diversity, as assessed during a median follow-up at 13 months after eradication therapy. However, post-eradication patients had less diversity than that in the controls and possessed a lower abundance of the five genera mentioned above. The eradication of H. pylori also altered the bacterial composition, but not to the same extent as that in controls. The microbial communities could be clustered into three separate groups: H. pylori-negative, pre-eradication, and post-eradication. Conclusion  Changes in dysbiosis may persist long after the eradication of H. pylori in patients with a history of GC. Dysbiosis may be involved in the development of both primary and metachronous GC after the eradication of H. pylori in such patients. Keywords  Dysbiosis · Gastric cancer · Helicobacter pylori · Eradication

Introduction

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1012​0-020-01141​-w) contains supplementary material, which is available to authorized users. * Toshio Watanabe [email protected]‑cu.ac.jp 1



Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1‑4‑3 Asahi‑machi Abeno‑ku, Osaka, Japan



RIKEN Center for Integrative Medical Sciences Laboratory for Microbiome Sciences, Yokohama, Kanagawa, Japan

2

Helicobacter pylori was classified by the World Health Organization as a type I carcinogen in 1994 [1, 2]. Approximately, 89% of non-cardia gastric cancers (GCs), accounting for 78% of total GCs, are attributable to H. pylori infection [3]. Several