P0184 Molecular signature of bowel urgency in Ulcerative Colitis
Authors: Pakpoor J , Hosack T , Sharma O , Teague R , Matini L , Kormilitzin A , Hutton K , Walsh A , Friedrich M , Travis S 
Published: January 2025

Background

Bowel urgency is a ‘top three’ symptom of concern to patients with ulcerative colitis (UC), but the mechanisms are unclear [1]. Determining the molecular signatures of bowel urgency would reveal targetable mechanisms and generate measurable endpoints for future use.

Methods

Clinical data from the Oxford University Hospitals real world cohort were analysed. Oxford patient-reported Simple Clinical Colitis Activity Index (SCCAI) scores (including bowel urgency scale 0-3) were extracted from the TrueColours-IBD remote monitoring platform [2], which includes 2,186 patients with UC. Contemporaneous routinely scored endoscopic (UCEIS) and histological (Nancy index) activity were extracted from medical records. Molecular RNA-sequencing (RNAseq) signatures were generated from diagnostic biopsies.

Results

Overall, bowel urgency showed weak-to-moderate correlations (Spearman correlation coefficient &lt;0.4) with clinical laboratory (CRP, albumin and haemoglobin), endoscopic (UCEIS) and histological (Nancy histologic index) measures of disease activity. By contrast, bowel urgency correlated moderately-to-strongly (Spearman correlation coefficient &gt;0.6) with most other patient-reported symptom measures (bowel frequency, general wellbeing and total SCCAI). Based on bulk RNAseq profiling from biopsies of patients with UC obtained within two weeks of a reported SCCAI, we defined molecular signatures of cellular contractility, lymphocyte activation, B cell immunity and chemotaxis. Molecular signatures that most strongly correlated with objective markers of inflammation (such as endoscopic and histological measures) were also correlated with reported bowel urgency [FIGURE 1]. However, there were notable cases of discordance between urgency and objective measures of inflammation [FIGURE 2].

Conclusion

At a cohort level, bowel urgency correlates with laboratory, endoscopic and histological measures of UC, but most strongly correlates with other patient reported symptoms indicative of disease activity. In corroboration, at a molecular RNA-level, bowel urgency similarly correlates with endoscopic and histologic markers of disease severity. However, on a patient-level there is a notable subset of patients with UC who demonstrate discordance between patient-reported urgency and objective markers of inflammation. Together, this suggests the presence of both overlapping and non-overlapping mechanisms of the symptomatic experience of urgency and bowel inflammation, which we are dissecting at a cellular level.

References

1.Travis S, Potts Bleakman A, Dubinsky MC, et al. The Communicating Needs and Features of IBD Experiences (CONFIDE) Study: US and European patient and health care professional perceptions of the experience and impact of symptoms of moderate-to-severe ulcerative colitis. Inflamm Bowel Dis. 2024;30(6):939-949. doi:10.1093/ibd/izad142

2.Walsh A, Matini L, Hinds C, et al. Real-time data monitoring for ulcerative colitis: patient perception and qualitative analysis. Intest Res. 2019;17(3):365-374. doi: 10.5217/ir.2018.00173