Abstract

Eradication of Helicobacter pylori has been found to be effective for gastric cancer prevention, but uncertainties remain about the possible adverse consequences such as the potential microbial dysbiosis. In our study, we investigated the association between gut microbiota and H. pylori-related gastric lesions in 47 subjects by deep sequencing of microbial 16S ribosomal RNA (rRNA) gene in fecal samples. The dominant phyla in fecal samples were Bacteroidetes, Firmicutes, and Proteobacteria with average relative abundances of 54.77, 31.37 and 12.91%, respectively. Microbial diversity analysis showed that observed species and Shannon index were increased in subjects with past or current H. pylori infection compared with negative subjects. As for the differential bacteria, the average relative abundance of Bacteroidetes was found to significantly decrease from H. pylori negative (66.16%) to past infection group (33.01%, p = 0.007), as well as from normal (76.49%) to gastritis (56.04%) and metaplasia subjects (46.83%, p = 0.027). For Firmicutes and Proteobacteria, the average relative abundances showed elevated trends in the past H. pylori infection group (47.11, 20.53%) compared to negative group (23.44, 9.05%, p = 0.068 and 0.246, respectively), and similar increased trends were also found from normal (18.23, 5.05%) to gastritis (35.31, 7.23%, p = 0.016 and 0.294, respectively) or metaplasia subjects (32.33, 20.07%, both p < 0.05). These findings suggest that the alterations of fecal microbiota, especially the dominant phyla of Bacteroidetes, Firmicutes and Proteobacteria, may be involved in the process of H. pylori-related gastric lesion progression and provide hints for future evaluation of microbial changes after H. pylori eradication.

Highlights

  • Gastric cancer (GC) is a major health problem in China, accounting for over 40% of the new GC cases annually worldwide (Torre et al, 2015)

  • The relative abundances of the dominant phyla Bacteroidetes, Firmicutes, and Proteobacteria in fecal microbiota were altered in subjects presenting with H. pylori infection and gastric precancerous lesions

  • Several gastric and intestinal microbes have been recently shown as procarcinogens in GC and colorectal cancer (Jo et al, 2016; Wang et al, 2016; Flemer et al, 2017; Coker et al, 2018; Ferreira et al, 2018), or probiotics enhancing immunotherapy response of cancer patients (Gopalakrishnan et al, 2018), while little has been reported about microbiota composition in precancerous lesions

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Summary

Introduction

Gastric cancer (GC) is a major health problem in China, accounting for over 40% of the new GC cases annually worldwide (Torre et al, 2015). The balance of commensal microbiota in the gastrointestinal tract may play important roles for regulation of host mucosal immune response, energy metabolism, elimination of pathogens and cancer development (Garrett, 2015; Rooks and Garrett, 2016). Many previous studies suggested that gastric microbiota can be affected by H. pylori infection (Maldonado-Contreras et al, 2011; Jo et al, 2016; Schulz et al, 2018). Dysbiosis of gastric microbiota and some specific bacteria were found to be associated with GC or precancerous lesions (Eun et al, 2014; Coker et al, 2018; Ferreira et al, 2018). Little is known about the association between intestinal microbiota and H. pylori infection or GC and precancerous lesions in human beings. Since it is well appreciated that microbiota composition shape immune responses at a local and systemic level, and that GC development is influenced by inflammatory signaling, it is tempting to speculate that H. pylori associated alterations of the gut microbiota may in turn influence GC development

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