Hepatocellular carcinoma (HCC) remains a major global health challenge with limited long-term survival despite advances in surgical, locoregional, and systemic treatments. Although immune checkpoint blockade (ICB) has reshaped HCC therapy, only a subset of patients achieves durable responses, reflecting substantial heterogeneity in tumor biology and immune microenvironments. Dysbiosis, involving the loss of beneficial bacteria, like Lactobacillus reuteri and Akkermansia muciniphila, and the expansion of pathogens, such as Klebsiella pneumoniae and Catenibacterium mitsuokai, drives HCC by promoting microbial translocation and chronic inflammation. This process is mediated by microbiota-derived metabolites. Pro-carcinogenic agents, like deoxycholic acid (DCA) and quinolinic acid, induce inflammation and activate oncogenic pathways, while protective short-chain fatty acids (SCFAs), like acetate and butyrate, modulate T-cell and ILC3 responses to influence antitumor immunity. Tryptophan catabolites, acting via the aryl hydrocarbon receptor (AhR), further fine tune immune and barrier functions. In addition, emerging data implicate intratumoral microbiota as active modulators of immune suppression and metastatic behavior. These mechanistic insights have accelerated the development of microbiome-targeted interventions, such as probiotics, prebiotics, engineered bacterial strains, and fecal microbiota transplantation, to enhance ICB responsiveness. This review synthesizes current advances linking the gut microbiome to HCC immunobiology and highlights emerging therapeutic strategies aimed at optimizing immunotherapy through precise microbial modulation.

Colorectal cancer (CRC) remains a major global health burden with the gut microbiome emerging as a critical contributor to tumor initiation and progression. Advances in high-throughput sequencing have deepened our understanding of host-microbe interactions across genomic, transcriptomic, epigenomic, and metabolomic levels. This review synthesizes current knowledge on how microbial communities shape colorectal carcinogenesis, including induction of genomic instability, remodeling of host transcriptional and epigenetic landscapes, and reprogramming of metabolic pathways within the tumor microenvironment. Integrative multi-omics strategies and advanced computational tools are powerful means for dissecting these complex biological systems. However, analytical challenges, such as data compositionality, sparsity, and high dimensionality, still hinder meaningful interpretation. Emerging technologies, like long-read sequencing and bacterial single-cell spatial transcriptomics, are enhancing the resolution and accuracy of microbiota profiling. Finally, the convergence of advanced experimental models, artificial intelligence-driven computational integration, and precision microbiome medicine are highlighted as key avenues for translating microbiome insights into preventive, diagnostic, and therapeutic innovations in CRC.

Colorectal cancer (CRC) is among the most common malignant tumors and remains a leading cause of cancer-related mortality worldwide. The gut microbiota and metabolites, which are modulated by host genetics and environmental exposures, have emerged as key contributors to the pathogenesis of CRC. A key feature of gut dysbiosis in CRC is the enrichment of pathogenic bacteria alongside the depletion of beneficial commensals. Probiotic supplementation has been shown to counteract this imbalance and suppress tumor progression. Mechanistically, probiotics suppress CRC development through multifaceted actions, including directly inhibiting tumor cell growth, reducing inflammation, reinforcing the intestinal barrier, and reprogramming host immunity. This review summarizes evidence on the inhibitory role of probiotics in CRC, evaluates the potential of probiotics as predictive biomarkers, and discusses microbiome-modulation strategies designed to enhance immunotherapy and chemotherapy, thereby offering a complementary paradigm for CRC prevention and treatment.

The human microbiome is increasingly recognized as a key contributor to the tumor microenvironment (TME). Advances in sequencing technologies have revealed the pivotal role of intratumoral microbiota in the development of gastrointestinal cancers. This review summarizes current knowledge on the characteristics and functional mechanisms of tumor-resident bacteria in colorectal, gastric, and hepatocellular carcinoma. We describe how these microbes affect carcinogenesis and disease progression through multiple pathways, including interactions between the microbiota and the host gut barrier, tumor cells, anti-tumor immunity, and other non-cellular components of the TME. In addition, the translational potential of intratumoral microbiota as diagnostic and prognostic biomarkers, as well as the influence on therapeutic responses, is discussed. A growing understanding of tumor-microbe interactions not only deepens insight into cancer biology but also opens new directions for innovative diagnostic and therapeutic strategies, highlighting the potential of targeting the intratumoral microbiome to improve patient outcomes in gastrointestinal oncology.

Gastric cancer (GC) remains one of the most prevalent malignancies of the gastrointestinal tract worldwide, ranking fifth in incidence and continuing to be a leading cause of cancer-related mortality. Elucidating the mechanisms underlying GC development and progression, as well as exploring effective preventive and therapeutic strategies, is therefore of paramount importance. Animal models are indispensable tools in this endeavor, providing platforms to investigate carcinogenic processes, recapitulate disease features, and evaluate therapeutic interventions, thereby bridging the gap between laboratory discoveries and clinical application. However, the establishment of reliable GC models remains challenging due to variations in tumor induction techniques, experimental conditions, and the profound heterogeneity and aggressive metastatic potential of GC. In this review we systematically summarize animal models used for studying gastric premalignant conditions and GC organized by disease stage. We analyze recent advances and limitations of each model, considering methodologic approaches, underlying mechanisms, and translational potential. Particular emphasis is placed on aligning model characteristics with contemporary clinical challenges. Ultimately, we highlight the pivotal role of animal models in advancing precision medicine for GC, offering novel perspectives to inform both mechanistic research and therapeutic development.

Immunogenic cell death (ICD), a special form of cell death, transforms “cold” tumors into “hot” tumors by fulfilling the following three key conditions: antigenicity; adjuvanticity; and a suitable tumor microenvironment (TME). Tumor cells release damage-associated molecular patterns (DAMPs) during ICD, thereby activating the dendritic–cytotoxic T cell axis to elicit systemic antitumor immune responses. However, drug resistance and immune-related adverse effects often limit traditional ICD inducers, including chemotherapy and radiotherapy. Notably, microbiota and microbial metabolites can trigger ICD in tumor cells, leading to the release of DAMPs, modulation of immune cell functions, and TME remodeling. This study comprehensively reviews the mechanisms underlying ICD regulation via microbiota and microbial metabolites. In addition, this review examines emerging strategies, including engineered microbiota, microbial-based combination therapies (such as incorporating immune checkpoint inhibitors or chemotherapy), and dietary interventions. Despite challenges associated with individual microbiota variability and mechanistic complexity, this study highlights the potential of microbiota-mediated ICD modulation as a novel paradigm for personalized cancer therapy, thereby providing insights for future directions of scientific research.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies of the digestive system, with a 5-year survival rate of only 13%, which is largely due to late-stage diagnosis and limited therapeutic options. Emerging evidence indicates that the gut microbiota has a critical role in PDAC tumorigenesis, progression, and therapeutic response. This review comprehensively summarizes current insights into gut microbiota-PDAC interactions, highlighting microbial alterations across taxonomic, functional, and clinical dimensions. Gut dysbiosis, which is marked by depletion of beneficial species and enrichment of pathogenic taxa, contributes to carcinogenesis through chronic inflammation, immune dysregulation, and metabolic reprogramming. In particular, the loss of butyrate-producing bacteria reduces anti-inflammatory activity and weakens CD8⁺ T cell function, thereby promoting tumor development. In addition to initiation, the gut microbiota also shapes PDAC progression through direct translocation to pancreatic tissue and systemic regulation of the tumor microenvironment (TME), influencing immune cell dynamics and fostering therapeutic resistance. Clinically, distinct microbial signatures are emerging as potential diagnostic and prognostic biomarkers. Moreover, microbiota-targeted interventions, including probiotics, synbiotics, fecal microbiota transplantation (FMT), metabolite supplementation, and dietary modulation, show promise as adjunctive therapeutic strategies. However, significant challenges remain in defining causal mechanisms and translating these findings into practice. Future research should integrate multi-omics profiling with well-designed clinical trials to delineate the gut microbiota-PDAC interaction network, guide precision microbiota-based interventions, and ultimately enable earlier detection and personalized treatment of this lethal disease.