In the October 2024 issue of Cell Reports Medicine, Tindle et al. identified two Crohn’s disease (CD) molecular subtypes - immune-deficient infectious CD (IDICD) and stress and senescence-induced fibrostenotic CD (S2FCD) - through multi-omics and functional analyses of patient-derived organoids. Reactome pathway enrichment analysis revealed subtype-specific dysregulations. In IDICD, the Nuclear receptor transcription factor pathway, Butyrophilin family interactions, and Intestinal infectious disease events were upregulated while Cytokine signaling in immune system events were downregulated. In S2FCD, Oncogene- and Oxidative stress-induced senescence pathways were upregulated and Signaling by TGF-beta receptor complex events were downregulated suggesting distinct subtype-specific therapeutic strategies.
