The gut microbiome is no longer viewed as a mere spectator in cancer development; it is increasingly recognized as a key driver of tumor initiation, progression, and treatment response. Recent advances in high-throughput sequencing have unveiled intricate crosstalk between commensal bacteria, tumor cells, and the immune system, revealing that microbial dysbiosis can either fuel malignancy or enhance anti-tumor immunity. This growing understanding is shifting the paradigm from simply observing microbial changes to actively manipulating the microbiome for cancer prevention, diagnosis, and therapy.
Published in May 2026 in the journal Cancer Biology & Medicine, a special issue guest-edited by Professor Jun Yu from the Chinese University of Hong Kong features seven review articles spanning hepatocellular carcinoma, colorectal cancer, gastric cancer, and pancreatic ductal adenocarcinoma. The collection covers mechanistic roles of gut and tumor-resident microbiota, probiotics as adjuvant therapies, animal models for premalignant lesions, and immunogenic cell death modulation by microbial metabolites.
One review examines how gut dysbiosis—loss of beneficial bacteria such as Lactobacillus and Akkermansia and overgrowth of pathogens like Klebsiella pneumoniae—drives hepatocarcinogenesis through microbial translocation and chronic inflammation. Another comprehensive review outlines a multi-omics framework for decoding host-microbe interactions in colorectal cancer, emphasizing integration of metagenomics, transcriptomics, and metabolomics to identify actionable targets (DOI:10.20892/j.issn.2095-3941.2025.0762). A third article makes the case for probiotics as promising adjuncts to conventional therapy, highlighting their capacity to restore gut barrier function and modulate local immune responses.
Perhaps most transformative, a review on tumor-resident bacteria reveals how these previously overlooked inhabitants can serve as diagnostic and prognostic biomarkers while influencing therapeutic outcomes. Additional contributions cover animal models for gastric cancer research (DOI:10.20892/j.issn.2095-3941.2025.0576), the role of the microbiome in pancreatic cancer (DOI:10.20892/j.issn.2095-3941.2025.0650), and a mechanistic framework linking microbial metabolites to immunogenic cell death, which could help convert "cold" tumors into "hot" ones responsive to checkpoint inhibitors.
"This collection shows that the next phase of cancer research isn't about choosing between genetics, immunology, or microbiology—it's about understanding how these systems interconnect and learning to modulate them in concert," the authors noted. They explained that the microbiome works best not as an isolated factor but as an integral component of the tumor ecosystem, and that interventions—whether through fecal microbiota transplantation, engineered bacteria, or metabolite-based drugs—must be designed with this holistic view in mind.
These advances point toward a more integrated model for personalized cancer care. Microbiome-derived biomarkers could one day enable early detection of gastric and colorectal cancers through non-invasive stool tests. Probiotic formulations, tailored to individual gut profiles, might boost the efficacy of immune checkpoint inhibitors while reducing immune-related adverse events. Fecal microbiota transplantation, already explored in melanoma and other cancers, offers a practical path for reshaping the gut ecosystem to favor anti-tumor immunity. As these approaches mature, the line between diagnosis, treatment, and prevention will likely continue to blur, pushing cancer care closer to truly precision medicine—where the microbiome, once a forgotten ally, becomes an indispensable guide.
