Postbiotic-related host transcriptomic axes link tumour immune microenvironment, stage and survival in colorectal cancer.
- 1Division of Biochemistry, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. [email protected].
- 2R&D Department, Rahavard Afarinesh Kavir Company, Qom, Iran. [email protected].
Abstract
Background
The tumour immune microenvironment shapes colorectal cancer progression and therapeutic vulnerability, but host metabolic programmes linked to immune-inflamed tumour states remain incompletely defined. Microbiome-derived and postbiotic-related metabolites influence epithelial, stromal and immune signalling, yet their downstream tumour transcriptomic readouts have rarely been assessed as host-side indicators of immune microenvironment state.Methods
Four mechanistically defined postbiotic-related host axes were curated: short-chain fatty acid, tryptophan/AhR, polyamine and ferroptosis/redox. Axis scores were calculated as mean z-standardized expression of curated genes in TCGA colorectal cancers and evaluated in GSE39582. Associations with marker-based immune/stromal signatures, microsatellite instability, cytolytic activity, stage and overall survival were tested using Spearman correlations, Wilcoxon tests and Cox models with false-discovery-rate correction.Results
In TCGA, the tryptophan/AhR axis showed the strongest coupling to marker-based immune and myeloid signatures, including macrophage-, Treg-, NK-cell-, CD8 T-cell-, Th1-like and cytolytic-activity programmes. Tryptophan/AhR, short-chain fatty acid and ferroptosis/redox axes were enriched in MSI-H and immune-high tumours, whereas the polyamine axis showed weaker immune associations. Short-chain fatty acid and ferroptosis/redox axes decreased recurrently in advanced-stage disease across cohorts. No universal prognostic axis emerged, although the short-chain fatty acid axis retained a stage-adjusted association with improved overall survival in GSE39582.Conclusions
Postbiotic-related host transcriptomic axes provide interpretable tumour-level readouts connecting metabolic cues with immune microenvironment states in colorectal cancer. They should be considered hypothesis-generating host-side immune-context readouts rather than ready-to-use clinical signatures.
Related
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BibTeX
@article{akbariardabili2026postbioticrelated,
title = {{Postbiotic-related host transcriptomic axes link tumour immune microenvironment, stage and survival in colorectal cancer.}},
author = {Soroush Akbari-Ardabili},
journal = {Journal of translational medicine},
year = {2026},
month = jul,
doi = {10.1186/s12967-026-08738-2},
url = {https://europepmc.org/article/MED/42958298},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Postbiotic-related host transcriptomic axes link tumour immune microenvironment, stage and survival in colorectal cancer.
AU - Soroush Akbari-Ardabili
PY - 2026
DA - 2026/07/31
JO - Journal of translational medicine
DO - 10.1186/s12967-026-08738-2
UR - https://europepmc.org/article/MED/42958298
AB - Background The tumour immune microenvironment shapes colorectal cancer progression and therapeutic vulnerability, but host metabolic programmes linked to immune-inflamed tumour states remain incompletely defined. Microbiome-derived and postbiotic-related metabolites influence epithelial, stromal and immune signalling, yet their downstream tumour transcriptomic readouts have rarely been assessed as host-side indicators of immune microenvironment state.Methods Four mechanistically defined postbiotic-related host axes were curated: short-chain fatty acid, tryptophan/AhR, polyamine and ferroptosis/redox. Axis scores were calculated as mean z-standardized expression of curated genes in TCGA colorectal cancers and evaluated in GSE39582. Associations with marker-based immune/stromal signatures, microsatellite instability, cytolytic activity, stage and overall survival were tested using Spearman correlations, Wilcoxon tests and Cox models with false-discovery-rate correction.Results In TCGA, the tryptophan/AhR axis showed the strongest coupling to marker-based immune and myeloid signatures, including macrophage-, Treg-, NK-cell-, CD8 T-cell-, Th1-like and cytolytic-activity programmes. Tryptophan/AhR, short-chain fatty acid and ferroptosis/redox axes were enriched in MSI-H and immune-high tumours, whereas the polyamine axis showed weaker immune associations. Short-chain fatty acid and ferroptosis/redox axes decreased recurrently in advanced-stage disease across cohorts. No universal prognostic axis emerged, although the short-chain fatty acid axis retained a stage-adjusted association with improved overall survival in GSE39582.Conclusions Postbiotic-related host transcriptomic axes provide interpretable tumour-level readouts connecting metabolic cues with immune microenvironment states in colorectal cancer. They should be considered hypothesis-generating host-side immune-context readouts rather than ready-to-use clinical signatures.
SN - 1479-5876
ER -