P430 Distinct faecal bile acid profiles are associated with sustained remission following exclusive enteral nutrition (EEN) induction therapy in paediatric Crohn's disease

Exclusive enteral nutrition (EEN) is a first-line therapy to induce remission in paediatric Crohn’s disease (CD). However, many patients will relapse upon resuming normal diet and there are no validated measures to determine subgroups of patients who will benefit most from EEN. We recently demonstrated that the certain compositional features of gut microbiome are associated with relapse following EEN. Microbiome composition can impact the balance of intestinal bile acids (BA), which have important antimicrobial and immune functions. The goal of this study was to analyse the relationship between intestinal BA composition and response to EEN in paediatric CD. We performed faecal BA analysis on a biorepository of stool samples from 13 paediatric CD patients who were treated with EEN for 12 weeks and achieved remission as defined by wPCDAI <12.5. All patients received maintenance therapy with an immunomodulator. Of these 13 patients, 7 sustained remission (SR) and 6 relapsed within 3 months of EEN cessation (non-sustained remission (NSR)). Faecal BA quantification was performed by the Sick Kids Analytical Facility for Molecules (AFBM) by liquid chromatography tandem mass spectrometry (LC-–MS-MS) using the Biocrates Life Sciences Bile Acids Kit according to the manufacturer’s instructions. For samples with BA abundance above the limit of detection, the missing data were imputed using area ratios relative to internal standards. BA concentrations were not normally distributed according to D’Agostino-Pearson test, so data are presented as median [range] and compared between groups using the Mann–Whitney U test. NSR patients had significantly lower levels of secondary BA (deoxycholic acid (DCA) and lithocholic acid (LCA) prior to starting EEN: median LCA 1 [1–4] pmol/mg vs. 1976 [19–3163] pmol/mg (p < 0.05) and median DCA 2 [1–5] pmol/mg vs. 2605 [29–4288] pmol/mg (p < 0.05). NSR patients also exhibited higher levels of primary BA (cholic acid (CA) and chenodeoxycholic acid (CDCA)) at baseline and Week 12, although this was not significant. The ratio of primary to secondary BAs was profoundly increased in NSR patients compared with SR patients: median 318.4 [0.926–642.1] (p < 0.05) vs. median 0.005 [0.002–0.059]. Levels of primary and secondary BA did not change significantly over the course of EEN in either group, although secondary BA concentrations were slightly increased in NSR patients by Week 12 relative to baseline. We demonstrate that primary and secondary BA compositions in stool differed between patients who sustained remission following EEN vs. those who relapsed. BA profiling may be a useful microbiome metabolic marker to identify patients who will sustain remission longer following EEN therapy.

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