The emerging role of CRISPR-Cas systems in helicobacter pylori and the gut microbiota as regulators of gastrointestinal cancer risk.

Gastrointestinal cancers contribute to 26% of global cancer incidence and 35% of deaths, with major contributors such as Helicobacter pylori (H. pylori) infection, gut dysbiosis, and lifestyle factors. CRISPR-Cas systems, while best known for their role in bacterial adaptive immunity, also shape bacterial physiology and host-microbe interactions, yet their influence on gastrointestinal carcinogenesis is poorly understood. This review brings together current evidence on the functions of CRISPR-Cas systems in H. pylori and the gut microbiota, highlighting their potential impact on cancer risk, diagnostics, and therapy. Key themes synthesized in this review include their role in bacterial immunity, contributions to microbial imbalance and virulence regulation, and emerging applications in cancer detection, microbiome modulation, and precision oncology. CRISPR profiles are being explored as biomarkers, while engineered systems show promise in targeted editing, phage therapy, and highly sensitive diagnostic platforms such as Cas12a-based assays. Despite this progress, challenges remain, including the risk of off-target effects, technical difficulties in detecting CRISPR signatures within complex microbial communities, and a lack of longitudinal human studies. Overall, CRISPR-Cas systems are emerging as natural regulators of microbial ecology and as engineered tools with potential applications in gastrointestinal cancer research, diagnostics, and precision microbiome interventions.