Gastric microbes associated with gastric inflammation, atrophy and intestinal metaplasia 1 year after <i>Helicobacter pylori</i> eradication.

Abstract

<i>Helicobacter pylori</i> is associated with gastric inflammation, precancerous gastric atrophy (GA) and intestinal metaplasia (IM). We aimed to identify microbes that are associated with progressive inflammation, GA and IM 1 year after <i>H. pylori</i> eradication. A total of 587 <i>H. pylori</i>-positive patients were randomised to receive <i>H. pylori</i> eradication therapy (295 patients) or placebo (292 patients). Bacterial taxonomy was analysed on 404 gastric biopsy samples comprising 102 pairs before and after 1 year <i>H. pylori</i> eradication and 100 pairs before and after 1 year placebo by 16S rRNA sequencing. Analysis of microbial sequences confirmed the eradication of <i>H. pylori</i> in treated group after 1 year. Principal component analysis revealed distinct microbial clusters reflected by increase in bacterial diversity (p<0.00001) after <i>H. pylori</i> eradication. While microbial interactions remained largely unchanged after placebo treatment, microbial co-occurrence was less in treated group. <i>Acinetobacter lwoffii</i>, <i>Streptococcus anginosus</i> and <i>Ralstonia</i> were enriched while <i>Roseburia</i> and <i>Sphingomonas</i> were depleted in patients with persistent inflammation 1 year after <i>H. pylori</i> eradication. A distinct cluster of oral bacteria comprising <i>Peptostreptococcus</i>, <i>Streptococcus</i>, <i>Parvimonas</i>, <i>Prevotella, Rothia</i> and <i>Granulicatella</i> were associated with emergence and persistence of GA and IM. Probiotic <i>Faecalibacterium praustznii</i> was depleted in subjects who developed GA following <i>H. pylori</i> eradication. Functional pathways including amino acid metabolism and inositol phosphate metabolism were enriched while folate biosynthesis and NOD-like receptor signalling decreased in atrophy/IM-associated gastric microbiota. This study identified that gastric microbes contribute to the progression of gastric carcinogenesis after <i>H. pylori</i> eradication.