Abstract
BACKGROUND: The tumor microenvironment (TME) has become a critical focus in the diagnosis and treatment of cancer. The involvement of the microbiome in tumor initiation and progression underscores its potential as a promising biomarker and therapeutic target. Furthermore, microorganisms in the gut and other ecological niches play pivotal roles in shaping cancer immune surveillance and modulating responses to immunotherapy, acting as key mediators connecting gut health to cancer progression. Thus, investigating the intricate interplay between the TME and gut microbiota could offer valuable insights to advance personalized cancer therapies. AIM OF REVIEW: This comprehensive review explores the complex interactions between the gut microbiota, tumor-associated microbiota, and TME, examining their origins, diversity, connections, and therapeutic implications. We investigate the potential for gut microbiota to translocate to tumors, where they may directly impact the TME and influence cancer progression. We compile the current knowledge on the diversity of intratumoral microbiota across various cancer types and its effects on cellular, immune, and spatial heterogeneity within the TME. Furthermore, we assess the efficacy of various methods for characterizing and identifying intratumoral microbiome, emphasizing their importance in understanding their composition and function in the TME. We also explore the therapeutic potential of modulating the gut microbiota, highlighting strategies such as dietary interventions, fecal microbiota transplantation, probiotics, prebiotics, and synthetic biology approaches. We then address the challenges and future directions in this emerging field, emphasizing the need for standardized protocols, advanced sequencing technologies, and refined animal models to enhance our understanding of microbiota-cancer interactions. In conclusion, the gut microbiota represents a promising therapeutic target for cancer treatment. Harnessing the power of gut microbial modulation could lead to novel combinatorial strategies that improve clinical outcomes for cancer patients. Nevertheless, further research is essential to surmount existing challenges and translate these insights into impactful, personalized cancer therapies.