Integrated multi-omics of feces, plasma and urine can describe and differentiate pediatric active Crohn's Disease from remission.

Abstract

Background: This study aimed to obtain a holistic view of remission in pediatric Crohn's Disease (CD) by integrating six omics datasets from three anatomical compartments.

Methods: Patients with fecal calprotectin below 250 mg/kg were considered in remission (n = 27), above 250 mg/kg as having active disease (n = 31). Proteome and microbiomes (fungi and bacteria) were analyzed in feces. Metabolomes in feces, urine, and plasma. Datasets were integrated into a multi-omics model.

Results: The use of individual datasets shows multiple differences between remission and active disease. Integration yielded a good model (AUC of 0.8) predicting remission. The most important features in this model are fecal bacteria (40%), fecal metabolites (22%), fecal proteins (16%), plasma metabolites (12%), fecal fungi (6%), and urine metabolites (4%). The interactome reveals Ruminococcaceae and Faecalibacterium as key players, with a correlation between antifungal urine hydroxyphenyllactic acid and fecal fungi. Pathway analysis shows an association of purine metabolism with remission, independent of thiopurine use. Changes in purine metabolism are confirmed in a pediatric CD public dataset.

Conclusion: The pathways and correlations identified as playing a role in remission may remain undetectable if individual omics datasets or single anatomical compartments are used, highlighting the need for a holistic approach that integrates multiple datasets from multiple anatomical compartments.