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P029 Serum bile acids profiling in IBD patients treated with anti-TNFs

G. Roda*1, E. Porru2, K. Katsanos3, A. Skamnelos3, K. Kyriakidi3, D. K. Christodoulou3, C. Caliceti2, G. Fiorino1, S. Danese1, A. Roda2

1Humanitas Research Hospital, IBD Centre, Milan, Italy, 2Department of Chemistry ‘Giacomo Ciamician’, Alma Mater Studiorum, Bologna, Italy, 3Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece

Background

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), represents chronic conditions with a deficient intestinal absorption. This study represents the first attempt to screenshot bile acids (BAs) in a large cohort of IBD patients to evaluate changes under anti-TNFα chronic treatment.

Methods

Forty CD and 40 UC patients were prospectively enrolled and a fasting serum sample obtained. BAs were quantified by high-pressure liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ES-MS/MS). Up to 15 different BAs, medical parameters (disease location, time to diagnosis, treatments, disease severity, CRP, and hepatic biochemistry) where admitted to a principal component multi-variate statistical analysis (PCA) to assess whether it is possible to discriminate IBD from healthy conditions and treatment regimens.

Results

Fifty per cent of each group was in treatment with biologics drugs (CD-BIO or UC-BIO; golimumab, adalimumab or infliximab, vedolizumab) and 50% never received biological drug. Our model allowed a quite clear separation of patients into two main clusters, CD biologic-free patients (CD NO BIO) for negative values of PC1 and CD BIO for positive values along the same axe.. CD-BIO have an increase in total BAs (4.11 ± 1.23 µM) compared with CD NO BIO (1.98 ± 0.42 µM), reaching concentrations similar to healthy subjects (3.94 ± 2.12 µM). The most discriminating parameter contributing to the clustering is the concentration of secondary BAs which significantly increase after biological treatment (1.54 ± 0.83 µM) compared with CD NO BIO (0.44 ± 0.17 µM) and reach levels similar to healthy subjects (1.39 ± 0.86 µM ). The mean ratio between primary and secondary BAs decreases in CD BIO (2.25 ± 1.45) compared with untreated ones (4.00 ± 1.87) similarly to healthy individuals (1.93 ± 0.95). UC did not show any significant differences. Time to diagnosis and disease progression did not affect BAs composition. Disease extension was assessed and BAs composition was mostly affected in L1 CD patients. However, L2 and L3 showed an increase in BA after biological treatment.

Conclusion

These findings indicate that, in CD patients, anti-TNFs restore the efficiency of the BAs absorption. Of note, these results suggest that the passive absorption in the colon of the most lipophilic BAs (ie, secondary Bas) have been restored and therefore secondary BAs might serve as biomarker of the healing process. In this context, a systematic characterisation of the profile of all endogenous BAs, including secondary metabolites could be of great help in the evaluation of the illness gravity, strongly related both to the extent of the inflammation and the variation in the gut microbiota composition.