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* = Presenting author

P054 A simple biomarker for IBD associated dysbiosis : the ratio of iso-LCA/LCA indicates alteration of isomeration of bile acids in the intestinal lumen.

T. Bazin*1, C. Landman1, M. Charrier1, C. Hanotte1, L. Humbert1, L. Brot1, V. Leducq1, E. Quévrain1, J. Cosnes1, 2, L. Beaugerie1, 2, H. Sokol1, 2, P. Seksik1, 2, D. Rainteau1, M.-A. Maubert1

1UPMC, ERL INSERM 1157 / UMR7203, PARIS, France, 2APHP, Service gastroentérologie et nutrition, PARIS, France

Background

IBD associated dysbiosis is linked to bile acids (BA) dysmetabolism in the intestinal lumen such as alteration in the deconjugation, transformation and desulphatation of this pool of BA. Isomerization activity leads to isoforms with altered physio-chemical properties and functions, quantifiable by mass spectrometry (MS). The objective of our research was to study the impact of IBD associated dysbiosis on the alterations of luminal BA including the isomerization of BA and in particular isomerization of LCA (lithocholic acid) to iso-LCA, with the aim of identifying a biomarker for dysbiosis.

Methods

Faecal samples from patients with IBD (sex ratio M/F 0.75; average age 34 +/- 2.4 years, Crohn's disease n=25, ulcerative colitis n =27) in which activity was evaluated by the Harvey Bradshaw index and from 28 healthy subjects (Sex ratio 1.1, average age 28 +/- 2.7 years) were collected. The composition of the faecal microbiota was determined by qPCR and expressed as log10 bacteria per g stool; in parallel, concentration of faecal BA, expressed as percentage of total BA, was measured by LC-MS. Non-parametric statistical analysis, Wilcoxon, was used to compare microbiota composition and BA levels between patient and control groups. Correlation between groups was analysed by Spearman test. Search for a threshold of different markers of dysmetabolism was carried for the best diagnostic performance (IBD vs control).

Results

Dysbiosis was observed in patients suffering from IBD, compared to control, characterized by a deficit in Firmicutes, notably in C. leptum (8,9+/-0,1 vs 9,8+/-0,1 ; p<10-2) and in F. prausnitzii (9,5+/-0,2 vs 10,9+/-0,2 ; p<10-2) and an increase in E. coli (8,9+/-0,2 vs 8,4+/-0,2 ; p<0,05). Further, a decrease in conjugation, transformation and desulphatation was observed in IBD patients compared with control. Isomerisation of LCA (reported as Iso-LCA/LCA) was also decreased compared with control (10%+/-9 vs 20%+/-5 ; p <0,05) and was lower for patients in flare compared with those in remission (8,5%+/-8 vs 14%+/-4 ; p<0,05). Furthermore, ratio of iso-LCA/LCA was positively correlated with concentrations of C. Leptum (r=0.57) and F. prausnitzii (r=0.50). Using the ratio of iso-LCA/LCA as a marker for the diagnosis of IBD, threshold of 0.73, was superior to all other BA dysmetabolism markers giving a sensibility of 0.85, a specificity of 0.56, a positive predictive value of 0.79, a negative predictive value of 0.65 and an AUC of the ROC curve of 0.82.

Conclusion

In IBD associated dysbiosis, BA dysmetabolism Results in a decrease in isomerisation of BAs. Ratio of iso-LCA/LCA appears to be correlated with dysbiosis, IBD diagnosis and IBD activity, and in this context could provide a simple biomarker for dysbiosis.