The Gut–Brain Tumour Axis: Microbiome-Driven Mechanisms in Neuro-Oncology

The gut microbiome, including commensal bacteria, archaea, viruses and fungi, is increasingly recognized as playing a key role in brain health, with distinct microbiota profiles associated in the development and treatment of brain tumours (i.e glioma, glioblastoma). Microbe-derived metabolites/products can reach the brain via neural pathways and systemic circulation or, as more recently proposed, through gut microbiota translocation that locally impact the tumour growth and its microenvironment. Within the brain, microbial products modulate systemic immunity, blood-brain barrier integrity, and inflammatory responses, shaping the tumour's immune landscape. Together, these interactions define the gut-brain-tumour axis as a promising therapeutic target. The brain tumour microenvironment (TME), composed of a milieu of different type of cells surrounding and interacting with the cancer cells, has become a central focus in cancer research. However, a critical knowledge gap remains in our understanding of the crosstalk between gut microbiome and its derived metabolites in relation to the tumour microenvironment. Deciphering this interplay holds significant promise for identifying novel therapeutic targets and strategies for enhancing treatment efficacy and patient outcomes.

The TME act as a potent pro-oncogenic entity, supplying growth signals and nutrients while actively suppressing anti-tumour immunity. Critically, it also drives therapeutic resistance by creating physical and biochemical barriers. Although the mechanisms through which brain tumours co-opt the TME remain under investigation, key questions are raising: Do gut microbiota-derived factors contribute to the reprogramming of TME cell types? What are the mechanism driving astrocytes, microglia, and stromal cells, towards a pro-tumorigenic state? Translating microbiome research into clinical neuro-oncology faces significant hurdles. Indeed, mouse models inadequately replicate human glioma, and clinical data on interventions like pre-/pro-biotics are limited. Therefore, another major challenge lies in uncovering robust microbial biomarkers capable of guiding immunotherapy, a goal currently constrained by substantial technical variability and analytical limitations. Whilst microbiome-based strategies promise to overcome immunosuppression and improve treatment response, associated risks like immune-related adverse events require thorough investigation. Substantial translational gaps persist, requiring more research focused on mechanistic validation, biomarker standardization, and the safe clinical integration of microbiome-modulating therapies.

The scope of the Research Topic is to gain more knowledge on the role of gut microbiome on the brain cancer and to dig more on the correlation/causation on brain cancer onset and growth/invasion. To this aim and for the complexity of the object, studies carrying on ±omics analyses will be very much appreciated.

The theme of interest then are:
- Role of gut microbiome on primary and secondary (metastasis) brain tumours;
- Mechanisms of interaction between gut microbiome-derived factors and the TME, investigated using in vitro and in vivo approaches, organoid platforms, patient-derived xenografts, and genetically engineered (including humanised) mouse models.
- Clinical trial studies incorporating/integrating gut microbiome profiling with neuroimaging correlates/outcomes
- Microbiota-Imaging signatures as a functional reflection (readout) of the Gut-Brain-Tumour

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Article types

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

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: gut-brain axis, brain tumour, gut microbiome, metabolites, translational studies

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