Oncobiomics: Leveraging Microbiome Translational Research in Immuno-Oncology for Clinical-Practice Changes

Abstract

Growing evidence suggests that cancer should not be viewed solely as a genetic disease but also as the result of functional defects in the metaorganism, including disturbances in the gut microbiota (i.e., gut dysbiosis). The human microbiota plays a critical role in regulating epithelial barrier function in the gut, airways, and skin, along with host metabolism and systemic immune responses against microbes and cancer. Collaborative international networks, such as ONCOBIOME, are essential in advancing research equity and building microbiome resources to identify and validate microbiota-related biomarkers and therapies. In this review, we explore the intricate relationship between the microbiome, metabolism, and cancer immunity, and we propose microbiota-based strategies to improve outcomes for individuals at risk of developing cancer or living with the disease.

Keywords: biomarkers; cancer; diet; fecal microbiota transplantation; gut; immuno-oncology; immunotherapy; microbiome; microbiota.

Figure 1

A pipeline for developing biomarker-guided interventions in the microbiota field. We illustrate how clinicians might diagnose gut dysbiosis and inform therapy through fecal or blood-based markers. Fecal biomarkers include key bacterial taxa (e.g., Akkermansia, Faecalibacterium prausnitzii, and Fusobacterium nucleatum), the TOPOSCORE, the Gut Microbiome Health Index (GMHI), and miRNA signatures. Blood biomarkers include soluble mucosal addressing cell adhesion molecule-1 (sMAdCAM-1), metabolomic profiles, and antimicrobial IgA/IgG. Following the discovery, validation, and qualification phases, these biomarkers guide microbiota-centered interventions, with feedback from pharmacodynamic and kinetic assessments to refine treatment strategies.

Figure 2

Comedications influencing immune-oncology (I-O) therapy efficacy. Broad-spectrum (non-selective) antibiotics reduce immune-checkpoint inhibitors (ICI) response when administered near treatment, whereas targeted (narrow-spectrum) agents appear relatively safe. Proton pump inhibitors (PPIs) are similarly associated with poorer ICI outcomes, highlighting the need for careful prescribing. β-blockers exhibit context-dependent effects, showing potential benefits in certain malignancies but an uncertain impact in others.