Gut Microbiota-Mediated Inflammation and Tumorigenesis: Implications for Tumor Microenvironment and Therapeutic Response

The gut microbiota is an essential component required for sustaining a normal physiological balance. An imbalanced gut flora, also known as dysbiosis, has been implicated in cancer development and progression. Current studies emphasize that changes in microbial composition can promote tumor formation through a network of interconnected signaling pathways. These include prolonged inflammatory signaling, release of toxins from microbial species, and the production of genotoxic compounds that can damage host DNA and enhance mutations. Several pathways are involved in mediating these effects, such as signaling pathways involving inflammatory mediators like cytokines, oxidative stress, and transcription factors like NF-κB. These pathways individually and collectively can contribute to a tumor-supportive environment. Apart from the direct damage caused by the microbiota, they also play a major role in the modulation of the tumor microenvironment (TME), wherein they regulate the functioning of immune cells and also affect tumor interaction with surrounding tissues. Metabolites and microbial components can modulate differentiation of immune cells, their activation, and function, thereby shaping the tumor microenvironment. Dysbiosis has been associated with impaired immune surveillance and metabolic activity, and also influences the efficacy of cancer therapies. These findings emphasize the importance of microbial–immune interactions as key determinants of cancer progression. Altogether, the gut microbiota and their metabolites regulate the tumorigenesis process, and understanding their role provides important insights into TME interactions and cancer progression. This review summarizes the major pathways and mechanisms through which the gut microbiota and their metabolites contribute to tumorigenesis, with emphasis on inflammatory signaling pathways, microbial-derived toxic factors, iron metabolism and the interactions between the microbiota and the tumor microenvironment. Additionally, we discuss current therapeutic strategies aimed at enhancing the effectiveness of cancer treatment through modulation of gut microbiota, along with their potential applications in treatment strategies and as diagnostic biomarkers.