Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study

Gastroenterology. 2022 May;162(6):1635-1649. doi: 10.1053/j.gastro.2022.01.022. Epub 2022 Jan 25.


Background & aims: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

Methods: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived.

Results: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001).

Conclusions: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

Keywords: Colitis; Eosinophil; Eosinophilic Colitis; Inflammatory Bowel Disease; Transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Colitis, Microscopic*
  • Enteritis
  • Eosinophilia* / diagnosis
  • Eosinophilia* / genetics
  • Gastritis
  • Humans
  • Inflammatory Bowel Diseases*

Supplementary concepts

  • Eosinophilic enteropathy