P1062 Microbially Conjugated Bile Acids as Potential Predictive Biomarkers for Dietary Therapy Outcomes in Paediatric Crohn’s Disease
Authors: Van Der Kruk N , de Haas I M , Ghiboub M , de Waart D R , Sigall Boneh R , de Meij T G J , Wine E , de Jonge W J , D’Haens G R A M , van de Graaf S F J , van Limbergen J E 
Published: January 2025

Abstract

Background
Crohn’s disease (CD) exclusion diet with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) effectively induce remission in mild-to-moderate paediatric CD. This has been associated with a shift in gut microbiome and metabolome1. The specific mechanisms driving diet-induced remission remain unclear. Microbial biotransformation of bile acids (BAs) is an important metabolic function that has gained increased attention, as three novel microbially-conjugated bile acids (MCBAs) have been found in significantly higher concentrations in CD patients2. We aimed to investigate changes in these MCBAs, specifically Phenylalanocholic acid (Phe-CA), Tyrosocholic acid (Tyr-CA), and Leucocholic acid (Leu-CA), associated with dietary therapies in paediatric CD.

Methods
BAs and MCBAs concentrations at baseline (W0) and week 6 (W6) were quantified using high performance liquid chromatography in available faecal samples from 23 treatment-naive mild-to-moderate-paediatric CD patients receiving either CDED+PEN (n=12) or EEN (n=11) in a prior RCT3. Clinical remission was defined as PCDAI ≤10. Two comparisons were conducted: (1) W6 remission vs. non-remission to identify if BAs were associated with clinical outcome at W6, and (2) baseline responders (achieving remission at W6) vs. non-responders to identify BAs predictive of W6 remission. ROC analysis and random forest were used to evaluate the predictive power of BAs for clinical remission.

Results
At W6, 19/23 patients achieved remission (CDED+PEN 9/12, EEN 10/11). Baseline clinical characteristics were comparable between patients achieving remission and no remission. Phe-CA was detected in most samples (19/23 at W0, mean=1.609µM; 12/17 at W6, mean=0.937µM), with W6 levels showing no significant association with clinical outcomes. None of the samples contained detectable levels of Tyr-CA, while only one sample contained detectable Leu-CA. Among CDED+PEN patients, baseline Phe-CA was significantly higher in those who did not achieve remission vs. those who achieved remission at W6 (p&lt;0.0001). ROC analysis of baseline Phe-Ca, 18 other BAs, and their ratios revealed no significant predictive power for clinical outcomes.

Conclusion
Baseline faecal Phe-CA concentration may serve as a predictive biomarker for CDED+PEN induced remission in paediatric CD. This effect seems independent of other BAs, indicating a unique role of Phe-Ca that could reflect either a specific microbial metabolic activity or the presence of distinct microbiome species. These findings underscore the potential significance of MCBAs in CD and dietary therapies. However, validation in a larger, prospective study is necessary to elucidate the relationship among MCBAs, CD, the microbiome, and diet-induced remission.

References
1.Verburgt CM, Dunn KA, Ghiboub M, et al. Successful Dietary Therapy in Paediatric Crohn’s Disease is Associated with Shifts in Bacterial Dysbiosis and Inflammatory Metabotype Towards Healthy Controls. J Crohns Colitis. Jan 27 2023;17(1):61-72. doi:10.1093/ecco-jcc/jjac105
2.Quinn RA, Melnik AV, Vrbanac A, et al. Global chemical effects of the microbiome include new bile-acid conjugations. Nature. 2020/03/01 2020;579(7797):123-129. doi:10.1038/s41586-020-2047-9
3.Levine A, Wine E, Assa A, et al. Crohn’s Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. Aug 2019;157(2):440-450.e8. doi:10.1053/j.gastro.2019.04.021