In Vivo Analysis of the Viable Microbiota and Helicobacter pylori Transcriptome in Gastric Infection and Early Stages of Carcinogenesis

Abstract

Emerging evidence shows that the human microbiota plays a larger role in disease progression and health than previously anticipated. Helicobacter pylori, the causative agent of gastric cancer and duodenal and gastric ulcers, was early associated with gastric disease, but it has also been proposed that the accompanying microbiota in Helicobacter pylori-infected individuals might affect disease progression and gastric cancer development. In this study, the composition of the transcriptionally active microbial community and H. pylori gene expression were determined using metatranscriptomic RNA sequencing of stomach biopsy specimens from individuals with different H. pylori infection statuses and premalignant tissue changes. The results show that H. pylori completely dominates the microbiota not only in infected individuals but also in most individuals classified as H. pylori uninfected using conventional methods. Furthermore, H. pylori abundance is positively correlated with the presence of Campylobacter, Deinococcus, and Sulfurospirillum. Finally, we quantified the expression of a large number of Helicobacter pylori genes and found high expression of genes involved in pH regulation and nickel transport. Our study is the first to dissect the viable microbiota of the human stomach by metatranscriptomic analysis, and it shows that metatranscriptomic analysis of the gastric microbiota is feasible and can provide new insights into how bacteria respond in vivo to variations in the stomach microenvironment and at different stages of disease progression.

Systematic review: gastric microbiota in health and disease

“…At the genus level, there were no significant differences between non‐atrophic gastritis and atrophy or intestinal metaplasia, but the genera Streptococcus , Prevotella and Actinomyces correlated with the diagnosis of atrophic gastritis with intestinal metaplasia in patients from Colombia . In addition, the dominance of Helicobacter in patients with gastric atrophy or intestinal metaplasia was heterogeneous with cases positive for H pylori and others negative or showing low H pylori abundance .…”

“…The majority of these studies were from Asian populations, but European and South American populations were also explored. Microbiota composition was assessed in gastric tissue specimens by amplification of DNA (six studies) or reverse‐transcribed RNA (in two studies; of the 16S rRNA gene or by metatranscriptomic RNA sequencing …”

Other Helicobacters and the gastric microbiome

“…These include two studies from India, two studies from Europe (UK and Austria) and single studies from China, Japan and Nicaragua. [33][34][35][36][37][38][39] Changes in the gastric microbiome were noted in all studies in response to H. pylori infection or different pathological states however other than H. pylori infection, there was no consistent gastric microbiome signature detected probably reflecting the importance of environmental influences. All studies noted reduced microbial diversity in H. pylori-infected groups, with one of the studies from India highlighting the ability of H. pylori to shape the constitution of the gastric microbiome but suggesting that other members of the Helicobacteraceae could also similarly influence community structure.…”

“…Several articles have also looked at the gastric microbiome in noncancerous and premalignant conditions as a result of H. pylori infection. These include two studies from India, two studies from Europe (UK and Austria) and single studies from China, Japan and Nicaragua . Changes in the gastric microbiome were noted in all studies in response to H. pylori infection or different pathological states however other than H. pylori infection, there was no consistent gastric microbiome signature detected probably reflecting the importance of environmental influences.…”

“…The first study to assess active gastric microbiome using metatranscriptomics (derived from RNA rather than genomic DNA) was published in 2017 . Assessing a cohort of patients undergoing endoscopy in Nicaragua, the gastric microbiome was detailed at different stages of H. pylori ‐induced pathology.…”