The Gut Microbiota-inflammation-immune Axis in Cancer: Anti-inflammatory Mechanisms and Therapeutic Implications.

Abstract

Through its mediation between inflammatory and immune pathways, the gut microbiota has proved to be a key regulator of cancer development, progression, and treatment response. Changes in microbial composition known as dysbiosis might facilitate chronic inflammation, immune dysregulation, and genomic instability, thereby facilitating carcinogenesis. Conversely, positive commensal microbes can generate short-chain fatty acids, bile acids, and tryptophan derivatives, which help maintain the epithelial barrier, cytokine signaling, and innate and adaptive immune responses. These microbial metabolites regulate immune cell differentiation, including regulatory T cells, dendritic cells, macrophages, and cytotoxic CD8+ T cells, thereby impacting the tumor microenvironment and tumor progression. Recent research highlights the microbiota as an outcome of response to cancer therapies, particularly immune checkpoint inhibitors, chemotherapy, and targeted therapies. Certain microbial genera, e.g., Akkermansia muciniphila, Bifidobacterium species, and Faecalibacterium prausnitzii, have been linked to augmented antitumor immunity and treatment efficacy. To enhance treatment outcomes and minimize toxicity during therapy, therapeutic interventions that target the regulation of the gut microbiome, such as dietary interventions, probiotics, prebiotics, fecal microbiota transplantation, and engineered microbial platforms, are under investigation. Moreover, improvements in metagenomics, metabolomics, and immunomics are now enabling the discovery of microbiome-based biomarkers to inform precision oncology. Knowledge of the gut microbiota-inflammation-immune axis thus presents promising possibilities in creating new treatment modalities and in designing individualized treatments in cancer management.