ObjectiveHelicobacter pyloriis 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 afterH. pylorieradication.DesignA total of 587 H. pylori–positive patients were randomised to receiveH. pylorieradication therapy (295 patients) or placebo (292 patients). Bacterial taxonomy was analysed on 404 gastric biopsy samples comprising 102 pairs before and after 1 yearH. pylorieradication and 100 pairs before and after 1 year placebo by 16S rRNA sequencing.ResultsAnalysis of microbial sequences confirmed the eradication ofH. pyloriin treated group after 1 year. Principal component analysis revealed distinct microbial clusters reflected by increase in bacterial diversity (p<0.00001) afterH. pylorieradication. While microbial interactions remained largely unchanged after placebo treatment, microbial co-occurrence was less in treated group.Acinetobacter lwoffii,Streptococcus anginosusandRalstoniawere enriched whileRoseburiaandSphingomonaswere depleted in patients with persistent inflammation 1 year afterH. pylorieradication. A distinct cluster of oral bacteria comprisingPeptostreptococcus,Streptococcus,Parvimonas,Prevotella, RothiaandGranulicatellawere associated with emergence and persistence of GA and IM. ProbioticFaecalibacterium praustzniiwas depleted in subjects who developed GA followingH. pylorieradication. 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.ConclusionThis study identified that gastric microbes contribute to the progression of gastric carcinogenesis afterH. pylorieradication.