Developing clinically relevant biomarkers using organoid epigenomics

At the Centre for Children’s Gut Health, we have pioneered a novel approach for biomarker discovery in paediatric Inflammatory Bowel Disease (IBD) by integrating epigenomic profiling with patient-derived intestinal organoids.

In our recent study (Dennison et al., Gut, 2024), we identified a highly specific DNA methylation (DNAm) signature within intestinal epithelial cells (IECs) that distinguishes children with IBD from non-IBD controls. Importantly, this epigenetic biomarker is:

• Stable and disease-associated, reflecting long-term inflammatory exposure rather than transient immune activation.
• Detectable in intestinal organoids cultured from patient biopsies, offering a robust, reproducible, and minimally invasive platform for biomarker screening.
• Clinically relevant, demonstrating strong correlation with histological inflammation and enabling accurate discrimination between IBD and non-IBD in validation cohorts.

This work represents a paradigm shift: rather than relying solely on immune or microbiome-based biomarkers, we show that the epithelial epigenome carries persistent molecular imprints of disease, offering a powerful and untapped source of diagnostic and prognostic information.

Furthermore, by leveraging organoid cultures, we can now track these biomarkers longitudinally, assess their modulation by therapy, and explore their functional impact using CRISPR-based gene perturbation. This lays the foundation for epigenetically-informed precision medicine in paediatric IBD.

Our research underscores the importance of studying human tissue directly — using clinically matched samples and next-generation models — to uncover biomarkers that are both mechanistically insightful and clinically actionable.

Reference:

Dennison TW, Edgar RD, et al. Gut. 2024. doi:10.1136/gutjnl-2024-332043