P0651 Evaluating tryptophan as a biomarker for treatment success in Inflammatory Bowel Disease patients undergoing therapy
Authors: Maaß C , Hatem Y , Aden K , Marquardt J U , Solbach P 
Published: January 2025

Background

Patients with inflammatory bowel disease (IBD) display heterogenous responses to different treatment modalities suggesting distinct disease pathomechanisms. Herein, tryptophan (Trp) metabolism is associated with a range of chronic inflammatory disease, but the relevance to guide treatment decision in IBD remains unclear. Here, we sought to evaluate Trp serum level as a biomarker of treatment response in IBD in comparison to established disease biomarkers.

Methods

We analyzed and compared the serum levels of Trp and C-reactive protein (CRP) from patients with Ulcerative Colitis (UC) (n = 15) and Crohns Disease (CD) (n = 10). Longitudinal analyses of 100 serum Trp measurements were obtained and associated with inflammatory IBD markers during the induction period of various biological agents including TNF-α inhibitors (n=2), interleukin inhibitors (n=11), JAK inhibitors (n= 8), Sphingosine modulators (n=3) and integrin inhibitors (n=1).

Results

As expected, we found an inverse correlation between CRP and Trp (rs = -0.219, p = 0.045), indication a weak, negative correlation between the two variables across all patients. However, while this effect was predominantly observed in UC (r = - 0.317, p = 0.003), patients with CD showed no significant correlation between CRP and Trp levels (rs = -0.082, p = 0.763). In line with these findings, the observed correlation showed significant correlation in the different treatment modalities. Patients who received either interleukin- or JAK inhibitors displayed a stronger correlation (rs = -0.542, p = 0.001 and rs = - 0.358, p = 0.007 respectively), while patients receiving TNF-α-/ integrin inhibitors or Sphingosine-1-phosphate receptor modulators did not show a significant correlation.

Conclusion

Highlighting the heterogeneity of responses to different biologics, we observed a correlation between high serum Trp levels and a decline in biomarkers associated with a disease flare. These observations were most pronounced in patients with UC receiving treatment with interleukin- and JAK inhibitors suggesting potential therapeutic relevance in indicating early signs of successful induction treatment.

References

Wang S, van Schooten FJ, Jin H, Jonkers D, Godschalk R. The Involvement of Intestinal Tryptophan Metabolism in Inflammatory Bowel Disease Identified by a Meta-Analysis of the Transcriptome and a Systematic Review of the Metabolome. Nutrients. 2023 Jun 26;15(13):2886. doi: 10.3390/nu15132886. PMID: 37447212; PMCID: PMC10346271.

Ding, Xueyan, Bin, Peng, Wu, Wenwen, Chang, Yajie, Zhu, Guoqiang, Tryptophan Metabolism, Regulatory T Cells, and Inflammatory Bowel Disease: A Mini Review, Mediators of Inflammation, 2020, 9706140, 10 pages, 2020. https://doi.org/10.1155/2020/9706140

Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M. Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J. Schwarz, Georg H. Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber,Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases,Gastroenterology,Volume 153, Issue 6,2017,Pages 1504-1516.e2,ISSN 0016-5085,https://doi.org/10.1053/j.gastro.2017.08.028.