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Background <p>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.</p> Methods <p>Patients with fecal calprotectin below 250 mg/kg were considered in remission (<i>n</i> = 27), above 250 mg/kg as having active disease (<i>n</i> = 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.</p> Results <p>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 <i>Ruminococcaceae</i> and <i>Faecalibacterium</i> 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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月8日

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  • Nienke Koopman,
  • Yorrick Jaspers,
  • Pim T. van Leeuwen,
  • Konstantinos Chronas,
  • Andrew Y. F. Li Yim,
  • Kay Diederen,
  • Anje A. te Velde,
  • Winfried Roseboom,
  • Angelika Kindermann,
  • Marc A. Benninga,
  • Gertjan Kramer,
  • Wouter J. de Jonge,
  • Stanley Brul,
  • Evgeni Levin,
  • Stephan Kemp,
  • Jurgen Seppen

摘要

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.