Introduction

Monitoring Crohn's Disease (CD) activity is crucial to identify disease progression and tailor treatment. Endoscopic scores are the most reliable tools to monitor disease activity but have some cost and risk implications. Inflammatory faecal biomarkers, such as Faecal Calprotectin (FC), are cost-effective and non-invasive but do not always correlate with endoscopic indexes. There is a need to develop alternative or complementary biomarkers that provide a more accurate assessment of CD activity.

Aims & Methods

The aim of this study was to identify faecal microbial biomarkers that could provide greater performance than FC to monitor activity, leading to improved management of CD.
A cohort of 55 CD patients was recruited from four Spanish hospitals. All participants provided a faecal sample before undergoing colonoscopy, which was analysed for FC levels and microbial markers, including Eubacteria (EUB), Escherichia coli (ECO), Faecalibacterium prausnitzii (FPRA) and its phylogroups I and II (PHG-I and PHG-II), Ruminococcus sp. (RUM), Akkermansia muciniphila (AKK), Methanobrevibacter smithii (MSM), Clostridium cluster I (CLO), Enterococcus sp. (ENT), Roseburia intestinalis (ROS), Clostridium cluster XIV (XIV), and Gammaproteobacteria (GAM). The Simplified Endoscopic Score for Crohn’s Disease (SES-CD) was employed to assess endoscopic activity, being remission and activity defined as SES-CD<2 and SES-CD≥2, respectively.

Results

FC levels showed a significant correlation with SES-CD (r_s=0.778, p<0.001) and a cut-off of 250 μg/g discriminated activity and remission with 86.21% sensitivity, 80.77% specificity, 83.33% positive predictive value, 84.00% negative predictive value, and 83.63% accuracy. The relative abundance of each microbial marker was compared between activity and remission and significant differences were identified in ECO (p<0.001), GAM (p<0.001), MSM (p=0.012), AKK (p=0.024), and RUM (p=0.026). The relative abundance of ECO (r_s=-0.495, p<0.001), GAM (r_s=-0.492, p<0.001), MSM (r_s=0.378, p=0.005) and RUM (r_s=0.274, p=0.042) also showed a significant correlation with SES-CD. None of the microbial markers alone exceeded FC performance. Abundances of microbial markers did not show significant differences when clinical variables such as the Harvey-Bradshaw index, disease location, and body mass index were compared. Only RUM (p=0.011) and ENT (p=<0.001) were found to be significantly different when the sexes were compared, though only in active CD.
The combination of ECO, RUM, GAM, XIV, PHG-I, and PHG-II in a unique microbial signature performed better than FC for discriminating between activity and remission, with 96.57% sensitivity, 96.87% specificity, 95.65% positive predictive value, 96.39% negative predictive value, and 96.25% accuracy.

Conclusion

A new faecal microbial signature has been defined to monitor endoscopic activity in CD with sensitivity, specificity, and accuracy higher than FC. This tool may be useful to improve clinical decision support systems in CD management, optimizing endoscopic allocation and providing a more patient-friendly and cost-effective approach. Further studies are needed to validate these results.

Disclosure

M. Serra-pagès, S. Ramió-Pujol, J. Amoedo, M. Malagón and S. Taboada-López are employees of GoodGut SLU.