Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

Abstract

ABSTRACTObjectiveSeveral conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk.Design95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq).ResultsSamples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase.ConclusionAutoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.SIGNIFICANCE OF THIS STUDY1.What is already known about this subject?Some conditions which result in reduced gastric acid secretion and hypochlorhydria are associated with an increased risk of gastric tumourigenesis.This risk is different in patients with H. pylori-induced atrophic gastritis, autoimmune atrophic gastritis and chronic proton pump inhibitor use.Hypochlorhydria and H. pylori infection cause alterations in the composition of the gastric microbiota.2.What are the new findings?We used 16S rRNA sequencing to characterise the microbiota in gastric corpus biopsies from a well characterised cohort of patients.The gastric microbiota was different in patients who were hypochlorhydric as a result of H. pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.Biochemical pathways associated with gastric carcinogenesis such as the fumarate reductase pathway were predicted to be altered in patients with atrophic gastritis.3.How might it impact on clinical practice in the foreseeable future?Understanding how the microbiota that colonise the hypochlorhydric stomach influence gastric carcinogenesis may ultimately permit stratification of patients’ subsequent tumour risk.Interventions that alter the composition of the gastric microbiome in hypochlorhydric patients with atrophic gastritis should be tested to investigate whether they alter the subsequent risk of developing gastric malignancy.