Long-term persistence of gastric dysbiosis after eradication of Helicobacter pylori in patients who underwent endoscopic submucosal dissection for early gastric cancer

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; Eradication; Gastric cancer; Helicobacter pylori.

Fig. 1

Comparison of α-diversity in the gastric microbiome between different gastric regions or H. pylori status. The numbers of observed OTUs (a) and indices of Chao1 (b), ACE (c), and Shannon (d) in each group have been expressed as medians and interquartile ranges. e The P values between different groups are shown. Wilcoxon rank sum test was used to compare the values of H. pylori-negative patients with those of patients in the pre-eradication or post-eradication groups. The Wilcoxon signed-rank test was used to compare the difference in the paired samples from the pre- and post-H. pylori eradication groups

Fig. 2

β-Diversity distances between different H. pylori groups using principal coordinate analysis (PCoA). a Unweighted UniFrac PCoA. b Weighted UniFrac PCoA. c PERMANOVA data comparing β-diversity of gastric bacterial communities between different H. pylori status groups using unweighted and weighted UniFrac distances

Fig. 3

Correlation between the abundance of H. pylori and α-diversity of the gastric microbiome. Correlation between the abundance of H. pylori and the number of observed OTUs (a), Chao1 index (b), ACE index (c), and Shannon index (d). Correlation was determined using Spearman's rank method

Fig. 4

Average relative abundances of taxa in the stomach of H. pylori-negative, pre-eradication, and post-eradication patients. Changes in the phylum (a), genus (b), and species (c)

Fig. 5

Heatmap of the relative abundance of gastric taxa stratified by H. pylori status and gastric site. Wilcoxon rank sum test was used to compare the relative abundances of gastric taxa in H. pylori-negative patients with those in pre-eradication or post-eradication patients. The Wilcoxon signed-rank test was used to compare the difference in paired samples from pre- and post-H. pylori eradication groups