Association of Helicobacter pylori Infection with the Gastric Microbiota: A Scoping Review from a Molecular Diagnostic Perspective

Helicobacter pylori infection remains globally one of the main causes of chronic gastritis, gastroduodenal ulcer disease, and gastric adenocarcinoma. Although the stomach has been considered an almost sterile environment, molecular techniques have revealed a complex and dynamic gastric microbiome whose composition may vary with H. pylori infection status. This review presents current knowledge on the impact of H. pylori on the composition, diversity, and functional implications of the gastric microbiome, focusing on studies applying molecular diagnostic techniques such as conventional PCR, quantitative real-time PCR (qPCR), 16S rRNA gene sequencing, and shotgun metagenomics. A systematic literature search was conducted between January and March 2025, including all eligible studies published from 2006 to 2025 following the PRISMA methodology for exploratory reviews. Thirty studies met the inclusion criteria and were integrated into the qualitative synthesis, which included primary studies, secondary sources, and methodological studies. The evidence suggests that H. pylori infection is generally associated with decreased alpha diversity and increased relative abundance of Proteobacteria (especially Helicobacter), along with decreased abundances of Firmicutes, Actinobacteria, and Bacteroidetes. Several studies have reported associations between virulence factors (e.g., CagA and VacA) and alterations in the gastric microenvironment, reflecting microbial and host-related changes relevant to chronic inflammation and gastric carcinogenesis. From a diagnostic perspective, qPCR and sequencing-based methods enable detection of H. pylori, evaluation of virulence- and resistance-associated targets, and broader taxonomic and functional analyses. However, significant methodological heterogeneity, particularly concerning sample types, DNA extraction, 16S hypervariable regions, and bioinformatics platforms, limits comparability between studies. These findings underscore the need for standardized molecular methods to improve understanding of interactions between H. pylori and the microbiome, as well as their clinical implications.