Stool host transcriptome reveals gut epithelial cell states and immune dynamics for gastrointestinal diagnosis and monitoring

Whole-transcriptome sequencing of stool host RNA recovers a median of 6300 protein-coding genes across 285 libraries, enabling separation of CRC, IBD, and normal profiles.

• Why it matters: Colonoscopy is invasive and slow, and non-invasive options for gastrointestinal diagnosis and monitoring are limited.
• What they did: The approach sequences stool host RNA and quantifies epithelial versus immune contributions, then trains a three-class model; within IBD it compares a 15-gene neutrophil score to fecal calprotectin against endoscopic activity.
• The result: Epithelium contributes 81% and immune cells 11% of stool host mRNA in normal samples, with immune fractions increasing in CRC and IBD; the model achieves an area under the curve of 0.94–0.96, and the 15-gene score tracks endoscopic activity better than fecal calprotectin in the same stool.

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