A robustness-first cross-disease framework supports a candidate shared microbial redox axis and disease-specific metabolic divergence in colorectal cancer, Crohn’s disease, and liver cirrhosis
Cross-sectional analysis uncovers a shared microbial redox vulnerability in gut-associated diseases, suggesting conserved bacterial targets for multiple distinct disorders.
Key Points
To determine whether colorectal cancer, Crohn’s disease, and liver cirrhosis share conserved gut microbial vulnerabilities using an analytically robust cross-disease framework.
Conducted a secondary cross-sectional analysis using public gut metagenomic and serum metabolomic datasets from colorectal cancer, Crohn's disease, and liver cirrhosis.
Introduced maximin optimization to systematically benchmark 1,152 preprocessing and model configurations across six classification tasks.
Identified a candidate 19-species signature where Firmicutes bacterium CAG:41 was the sole threshold-stable cross-disease taxon consistently depleted across all three conditions.
Demonstrated functional pathway convergence on sulfur-selenium redox metabolism and B-vitamin biosynthesis alongside predominantly disease-specific host metabolomic responses.
Found that Crohn's disease and liver cirrhosis are dominated by single discriminative taxa, whereas colorectal cancer requires community-level integration (exploratory validation AUC = 0.769, 95% bootstrap CI 0.678–0.849).