Therapeutic regulation of gut microbiota in gastric cancer: mechanisms, strategies, and clinical prospects

Vollständiger Abstract

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Gastric cancer (GC) is a highly prevalent malignancy associated with substantial mortality worldwide. Dysbiosis of the gut microbiota is closely linked to the pathogenesis, clinical characteristics, and therapeutic responses of GC, making it a central focus of research in the field of tumor microecology. However, existing reviews mainly focus on microbial compositional features, individual mechanisms, or specific microbiota-based interventions, while lacking an integrated theoretical framework that incorporates Helicobacter pylori (HP) infection, multi-layer tissue injury, and systematic clinical strategies. Therefore, this review establishes a three-dimensional integrated framework encompassing etiology, injury, and intervention to provide a critical and comprehensive analysis. In the etiological dimension, we systematically summarize GC-associated gut microbiota alterations and their clinical relevance. In the injury dimension, we integrate multiple pathogenic processes, including mucosal barrier disruption, chronic inflammation, carcinogenic metabolite accumulation, epigenetic damage, tumor immunosuppression, and cancer-promoting signaling pathways, to elucidate the potential mechanisms by which the gut microbiota contributes to GC initiation and progression. In the intervention dimension, we systematically evaluate microbiota-modulating strategies, including probiotics, fecal microbiota transplantation, antibiotics, and microbial metabolites, and comparatively assess the evidence levels, advantages, and clinical limitations of these approaches. By integrating clinical studies, experimental models, and translational medical evidence, this review aims to establish a systematic and critical theoretical framework for GC microecological regulation, elucidate the potential and limitations of gut microbiota-based approaches in GC prevention and treatment, and provide new perspectives for the development of precision microecological intervention strategies in the future.