The microbiome and its impact on the epigenome in cancer.

The complex interplay between the human microbiome and epigenetic regulation represents one of the most rapidly evolving frontiers in cancer biology. The trillions of microorganisms residing in and on the human body collectively termed the microbiota may influence the host gene expression through epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA regulation. In cancer patients, is associated with disruption of the normal epigenetic landscape, contributing to oncogenesis, tumor progression, immune evasion, and therapeutic resistance. This review synthesizes current evidence on how specific microbial metabolites such as short-chain fatty acids, secondary bile acids, and folate derivatives modulate epigenetic marks in tumor cells and the tumor microenvironment. We further discuss the emerging concept of the "oncobiome" and examine how microbiome-epigenome crosstalk influences cancer risk, progression, and response to therapy including chemotherapy, immunotherapy, and epigenetic drugs. Finally, we explore the translational potential of microbiome modulation as an adjunct strategy in cancer epigenomics, highlighting key research gaps and future directions.