Microbiome-Onco Axis: Decoding Gut-Driven Pathways in Pancreatic, Colorectal, and Liver Cancer

The intestinal microbiome is emerging as a powerful architect of cancer risk, tumor evolution, and therapeutic response across colorectal, pancreatic, and liver malignancies. This Hot Topic invites mechanistic and translational studies that illuminate how gut community structure, function, and metabolites—alongside barrier integrity and host immunity—shape carcinogenic microenvironments and inter-organ crosstalk along the gut–liver and gut–pancreas axes. We particularly welcome work integrating microbial ecology with immunology, metabolomics, spatial profiling, organoid and gnotobiotic models, and robust longitudinal or causal designs to identify actionable pathways, biomarkers, and targets.

Submissions should primarily investigate the composition, function, or interactions of gut microbial communities in relation to cancer biology or clinical outcomes, including determinants of response and toxicity to chemotherapy, targeted agents, and immunotherapies. Studies exploring microbial genotoxins and metabolites, barrier dysfunction and bacterial translocation, stromal and immune remodeling, and precision interventions—dietary modulation, pre/pro/syn/postbiotics, bacteriophages, antibiotics stewardship, and FMT—are encouraged. Work that focuses solely on IT/web science or lacks a clear intestinal microbiome–cancer connection is out of scope; investigations of immune or gene expression changes are welcome when anchored to gut microbiome interactions. This Topic advances SDG 3 by catalyzing prevention, early detection, and personalized treatment strategies in CRC, PDAC, and HCC.

We welcome articles addressing, but not limited to, the following themes:

-Map microbial signatures and functions linked to early neoplasia and tumor progression in CRC, PDAC, and HCC.
-Define mechanistic roles of metabolites and genotoxins (e.g., secondary bile acids, colibactin) in oncogenic signaling and DNA damage.
-Dissect gut barrier integrity, mucus dynamics, and translocation as drivers of inflammation, fibrosis, and tumor niches.
-Elucidate microbiome-mediated modulation of host immunity, from myeloid training to T cell polarization and immunosurveillance.
-Characterize microbiome effects on tumor microenvironment remodeling across stromal, vascular, and immune compartments.
-Trace gut–liver and gut–pancreas communication via portal and lymphatic routes influencing oncogenesis and therapy response.
-Identify microbial and metabolite biomarkers for risk stratification, early detection, MRD, and treatment selection.
-Evaluate microbiome determinants of efficacy and toxicity for chemo, radiotherapy, targeted therapies, and checkpoint inhibitors.
-Test microbiome-targeted interventions (diet, pre/pro/syn/postbiotics, phages, FMT, stewardship) for mechanism, safety, and efficacy.
-Standardize multi-omics, spatial, causal inference, and reproducible pipelines to reduce confounding and enhance translation.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review

Keywords: intestinal microbiome, colorectal cancer, pancreatic cancer, liver cancer, tumor microenvironment, microbial metabolites, barrier dysfunction, immunotherapy response, multi-omics, precision oncology

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.