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.
Cancer remains notoriously difficult to treat, partly because tumors co‑opt their surrounding environment, including the resident microbiota, to evade immune surveillance and resist conventional therapies. While traditional oncology has largely focused on genetic and cellular alterations within tumor cells, the role of the gut and intratumoral microbiome has long been overlooked. However, new insights into how bacterial metabolites modulate host immunity, how tumor‑resident bacteria directly interact with cancer cells, and how microbial signatures correlate with clinical outcomes are opening unexpected avenues for intervention. Based on these challenges, deeper exploration is needed into how microbiome science and cancer biology can converge – not as separate disciplines, but as an integrated front for precision oncology.
Published in May 2026 in the journal Cancer Biology & Medicine, a special issue was guest‑edited by Professor Jun Yu from the Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease at The Chinese University of Hong Kong. The collection features seven review articles that span topics from hepatocellular carcinoma and colorectal cancer to gastric cancer and pancreatic ductal adenocarcinoma. Together, they cover the mechanistic roles of gut and tumor‑resident microbiota, the potential of probiotics as adjuvant therapies, the use of animal models to study premalignant lesions, and the emerging field of immunogenic cell death modulation by microbial metabolites.
Several articles showcase where microbiome‑based strategies are already gaining traction. 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 the integration of metagenomics, transcriptomics, and metabolomics to identify actionable targets. 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 also influencing therapeutic outcomes. Additional contributions cover animal models for gastric cancer research, the role of the microbiome in pancreatic cancer, 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. When we start treating the microbial community as a therapeutic partner, the boundaries between host and environment, between prevention and treatment, begin to dissolve.
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. For patients with bacteria‑infected tumors – often linked to poor prognosis – targeted antimicrobial or nanodrug strategies could simultaneously combat infection and malignancy. 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.
