Abstract
Abstract Background An ileal resection is known to cause bile acid malabsorption in Crohn’s disease (CD) 1, but its impact on the bile acid landscape remains understudied. Therefore, we studied bile acid composition in ileal fluid of CD and control patients using targeted metabolomics, and assessed the impact of sample preparation. Methods Ileal fluid was collected from CD patients (n=10) and non-IBD controls (n=10) having an ileostomy (patient characteristics in Table 1). Targeted metabolomics (LC-MS/MS) was applied on full ileal fluid samples as well as on their supernatants (ie. after centrifugation of a full fluid sample aliquot). Bile acid raw abundances were normalised to sample weight (g), and only bile acids detected in at least 40% of all samples (per sample type) were included for further analysis. A comparative analysis between full ileal fluid and its supernatants across all samples was assessed by Spearman correlations, while the bile acid abundances between CD and controls was compared using Mann-Whitney U tests. A nominal p value < 0.05 was considered significant. Results For the CD group, the median [min-max] length of resected ileum was 15.0 [0.0-33.5] cm and 0.0 [0.0-15.0] cm for the control group (Table 1). Ten primary, 6 secondary and 2 modified bile acids were present in full ileal fluid as well as in the corresponding supernatants. While bile acid abundances were 1.2 to 6.0 times higher in full ileal fluid compared to paired supernatants (Figure 1A), the overall bile acid profiles remained highly consistent. In particular, 13 out of 18 bile acids showed a strong correlation between both sample types (r>0.8, p<0.05), and the remaining 5 showed moderate but significant correlations (r=0.5-0.7, p<0.05). Lastly, while the abundances between the full CD and control groups were similar, a subanalysis comparing CD patients with an ileal resection (n=5) to controls with a total mesorectal excision (n=6), revealed an increase in primary bile acids glycocholic acid (GCA) (p=0.052) and glycochenodeoxycholic acid (GCDCA) (p=0.056) in the CD subgroup (Figure 1B). Conclusion In this pilot metabolomics study, we detected both primary and secondary bile acids in the ileal fluid of CD patients and controls. Bile acid composition in full ileal fluid aligns well with its derived supernatant, suggesting supernatant as a viable alternative for measurements, simplifying sample preparation. GCA and GCDCA, both primary bile acids typically reabsorbed in the ileum, tended to be increased after ileal resection in CD patients. A broader screening of bile acid and microbiota metabolites in ileal fluid on a larger scale may unravel novel targets contributing to disease recurrence after resection. References (1)Vitek L. Bile acid malabsorption in inflammatory bowel disease. Inflamm Bowel Dis. 2015;21(2):476-83
Published Version
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