Gastrointestinal inflammation and cancer: viral and bacterial interplay

Gastrointestinal (GI) inflammation and malignancies arise from complex interactions between the host’s immune responses and microbial pathogens. Epstein–Barr virus (EBV), Helicobacter pylori (H. pylori), and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to chronic GI inflammation, immune evasion, and tumorigenesis through distinct but interconnected mechanisms. EBV, a widespread herpesvirus, establishes a latent infection in B cells and epithelial cells. It promotes gastric carcinogenesis through immune modulation, epigenetic changes, and viral microRNAs (miRNAs). H. pylori, a gastric carcinogen, induces chronic gastritis and gastric cancer (GC) through Cytotoxin-associated gene A (CagA) and Vacuolating cytotoxin gene A (VacA) virulence factors. These factors disrupt host immune responses and enhance oncogenic signaling pathways. Recent evidence also links SARS-CoV-2 to gut dysbiosis and inflammatory responses. It worsens immune dysfunction and hence potentially impacting GI pathology. EBV and H. pylori co-infections may synergistically amplify inflammatory signaling, creating a tumor-promoting microenvironment. This review emphasizes the molecular mechanisms by which these pathogens contribute to GI diseases, focusing on their immune evasion strategies and potential therapeutic targets. Understanding these interactions is essential for developing targeted interventions for infection-driven GI malignancies.