Physiol Genomics. 2025 Sep 2. doi: 10.1152/physiolgenomics.00091.2025. Online ahead of print.

ABSTRACT

The human microbiome is emerging as a key regulator of cancer biology, modulating tumor development, immune dynamics, and therapeutic responses across diverse malignancies. In this review, recent insights are synthesized regarding how microbial communities (bacterial, fungal, and viral) shape oncogenic signaling, immune checkpoint blockade (ICB) efficacy, and metabolic reprogramming in lung, pancreatic, colorectal, breast, cervical, melanoma, and gastric cancers. Mechanistic links between microbial metabolites, intratumoral colonization, and host immune phenotypes are highlighted proposing that the microbiome constitutes a programmable axis within the tumor immune-metabolic ecosystem. Drawing on multi-omics integration and translational studies, a shift from associative profiling toward causal, spatially resolved, and intervention-ready frameworks is proposed. This perspective positions the microbiome not as a passive bystander, but as a co-evolving participant in tumor progression and treatment response, with the potential to reshape diagnostics, prognostics, and therapeutic strategies in precision oncology.

PMID:40897518 | DOI:10.1152/physiolgenomics.00091.2025