Alterations of human gastric microbiota in patients with H. pylori infection and different stages of gastric carcinogenesis

Abstract

Apart from H. pylori (HP), the distribution and significance of other bacteria in human stomach remains largely unknown. This study aims to characterize the gastric microbiota in individuals with and without HP infections; to determine the changes in gastric microbiota after HP eradication; and to demonstrate the difference in gastric microbiota in individuals with different histological stages of gastric carcinogenesis.

Endoscopic gastric biopsies were obtained from patients during scheduled endoscopies. All patients provided informed consent for participation into this study. HP status was determined by rapid urease test and histology. Bacterial 16S r RNA was sequenced on next generation sequencing platforms (454 pyrosequencing or Illumina MiSeq). Operational taxonomic unit (OTU) clustering, diversity indexes calculation, taxonomic classification, principle component (PC) analysis and statistical analyses were performed after quality control and raw sequence processing.

Hierarchical clustering and PC analyses of 24 HP-positive and 24 normal control samples demonstrated two cluster groups mainly based on HP. Diversity indexes calculation and OTU examinations revealed domination of HP in infected individuals. However, the domination was seen broken and the overall microbiota was restored in samples obtained 8 weeks after eradication treatments. To assess the alterations of gastric microbiota in different histological stages of gastric carcinogenesis, we recruited another 8 patients with HP gastritis, 9 with gastric intestinal metaplasia (IM), 7 gastric carcinoma and 8 normal controls who were negative for HP. Hierarchical clustering of these samples showed that they were mainly segregated by the presence of HP rather than by histological stages. Gastric cancer samples however had reduced bacterial diversity as compared to other histological groups. There were also significant differences in the abundance of different bacterial families between IM and cancer samples, but not between normal and IM samples.

H. pylori alters and ultimately dominates gastric microbiota, which could possibly be restored by antibiotic treatment. There are significant changes in the relative abundance of different bacterial species in the stomach during progression from IM to cancer. The gastric microbiota in cancer patients is distinctly different from pre-cancerous stages.