Bile Acid Metabolism Linked to Colorectal Cancer Prognosis

BILE acid metabolism was consistently suppressed in colorectal cancer and was associated with patient prognosis, according to a comprehensive multi omics analysis integrating transcriptomic, spatial, single cell, and microbiome data.

Metabolic reprogramming is a recognised feature of colorectal cancer, but the contribution of the bile acid metabolism pathway has remained unclear. To investigate its clinical relevance, researchers applied an integrative analytical framework combining bulk transcriptomics, single cell transcriptomics, spatial transcriptomics, and gut microbiome data. The findings were further validated using quantitative reverse transcription polymerase chain reaction on paired tumour and normal tissue samples from patients.

The analysis demonstrated widespread transcriptional suppression of the bile acid metabolism pathway in colorectal cancer tumours. Experimental validation confirmed significant downregulation of representative pathway genes, including ABCA8 and ABCD2, supporting the molecular findings observed across the multi omics datasets.

Prognostic Signature Predicted Overall Survival

Building on these findings, the investigators developed a 15 gene prognostic signature based on the bile acid metabolism pathway. The signature demonstrated a consistent association with overall survival across five independent patient cohorts, suggesting that pathway activity may have prognostic value in colorectal cancer.

Single cell transcriptomic analysis showed that bile acid metabolism activity was suppressed across epithelial tumour cell populations. Spatial transcriptomics added further biological context by demonstrating that pathway activity was enriched within metastatic stromal regions and consensus molecular subtype 3 (CMS3) tumour microenvironment niches. These findings highlighted differences in pathway activity across distinct cellular and spatial compartments within tumours.

Gut Microbiota Associations May Guide Future Research

The study also identified significant associations between bile acid metabolism and gut microbiota composition. Higher pathway activity was positively associated with members of the Clostridiales taxonomic group and negatively associated with Dorea longicatena, suggesting interactions between host metabolism and the intestinal microbiome.

Taken together, the findings indicated that suppression of bile acid metabolism is associated with prognosis in colorectal cancer and may represent a clinically relevant biological feature of the disease. The investigators concluded that this integrated multi omics framework provides a foundation for hypothesis driven biomarker discovery and supports further research into therapeutic strategies targeting bile acid metabolism in colorectal cancer.

Reference

Raeisi H et al. Integrative multi-omics analysis of bile acid metabolism as a prognostic determinant in colorectal cancer. Sci Rep. 2026;

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