Research advances in the role of circulating microorganisms in gastrointestinal tumors (Review).

Gastrointestinal tumors are common malignant tumors of the digestive system, which globally threaten human health. Notably, it has been discovered that blood and other circulating body fluids are not completely sterile; instead, they harbor complex and dynamic microbial DNA and signatures [circulating microorganisms (CM)]. These microorganisms primarily originate from the microbial translocation (including bacterial fragments, DNA and metabolites) through a compromised intestinal barrier, and are closely associated with the initiation and progression of gastrointestinal tumors, thus providing novel perspectives for early tumor diagnosis and prognosis. Although there is currently no evidence that CM can directly cause cancer, their metabolites and exosomes may contribute to tumor microenvironment remodeling. On one hand, they activate pattern recognition and inflammatory signaling pathways, such as Toll-like receptor/signal transducer and activator of transcription, potentially inducing and maintaining low-grade chronic inflammation. On the other hand, they may facilitate immune evasion, potentially promoting the 'inflammation-cancer' transition. With the development of metagenomic technologies and the maturation of next-generation high-throughput sequencing technologies, CM have shown potential as liquid biopsy biomarkers for the early diagnosis of gastrointestinal tumors. Interventions targeting specific CMs have also shown prospects for enhancing efficacy in early clinical trials. However, the field still faces numerous challenges, including insufficient depth of mechanistic validation and a lack of standardized detection protocols. Future efforts should aim to conduct further systematic research to clarify the biological functions and clinical translational value of CM in gastrointestinal tumors.