Deciphering intratumoral microbiota in digestive system tumors: mechanisms and emerging therapeutic strategies

Digestive system malignant tumors (DSMTs)—including gastric, pancreatic, colorectal, liver, and esophageal cancers—are major contributors to cancer-related deaths worldwide, owing to their increasing incidence and poor prognoses. Improving patient survival hinges on a deeper understanding of the mechanisms driving DSMT initiation, progression, and therapeutic resistance. This review offers a novel perspective by exploring DSMTs through the lens of the emerging concept of intratumoral microbiota. We outline the historical context and diverse origins of intratumoral microbiota, detailing their multifaceted roles in DSMTs pathogenesis. Additionally, we highlight innovative traditional Chinese medicine strategies that modulate the intratumoral microecosystem for DSMTs prevention and therapy. Finally, we critically assess the translational potential and current challenges associated with microbiota-targeted anticancer therapeutics. Adopting a microbiota-centric paradigm opens new avenues for next-generation precision oncology, aiming to improve outcomes for patients with DSMTs.