Progress in research on gut microbiota regulation of tumorigenesis, progression, and therapeutic response via inflammatory cytokines

Abstract

The gut microbiota has emerged as an important regulator of tumour biology through dynamic interactions with host immune and inflammatory networks. A growing number of preclinical studies and observational clinical studies suggest that dysbiosis-associated changes in microbial composition and metabolite profiles can remodel inflammatory signalling pathways and are associated with tumour initiation, progression, metastasis, and therapeutic response. Microbial components and metabolites can activate pattern-recognition receptor-related pathways, including nuclear factor kappa B (NF-κB), in cell and animal models. These changes may promote a tumour-supportive chronic inflammatory milieu or, under specific ecological conditions, help shape an immune-activated microenvironment. Current evidence also suggests that the gut microbiota and inflammatory cytokines may influence treatment response. Preclinical models and some patient cohort studies indicate that dysregulated inflammatory responses are associated with reduced chemotherapy tolerance and a higher risk of immune-related adverse events (irAEs), whereas certain beneficial microbial signals are associated with enhanced CD8 + T-cell activation and improved efficacy of immune checkpoint inhibitors (ICIs). However, these associations vary across cancer types and study populations, and their causality and clinical generalizability still require further validation. In this Review, we summarize current evidence on how the gut microbiota and inflammatory cytokines jointly regulate tumour development and therapeutic outcomes. We also discuss therapeutic strategies that target microbial composition and inflammatory signalling, with emphasis on their translational potential in precision oncology.