Abstract Background Fecal samples (FC) are commonly used to study inflammatory bowel disease (IBD), mainly reflecting luminal dietary and bacterial activity. In contrast, rectal swabs (RS) capture signals closer to the mucosal epithelial layer. This study aimed to compare metabolite profiles between FC and RS and to evaluate differences between IBD patients and healthy controls. Methods RS samples were collected during endoscopy after bowel cleanup. LCMS untargeted metabolomics with a predefined expanded library consisting of 803 metabolites was used for high-throughput metabolomics. Results This study includes two cohorts of metabolomics samples from IBD patients and control subjects, with each cohort independently processed and analyzed. Cohort 1 included 215 RS and 10 FC samples, and cohort 2 included 96 FC and 22 RS samples (19 that had paired FC/RS samples from the same subject). To define different signals between FC vs. RS samples (FDR0.1), we initially compared control non-IBD RS samples with FC samples in cohort 1, identifying 195 metabolites higher in RS and 176 higher in FC (Fig. 1A). We then applied paired comparisons on the 19 subjects in cohort 2, and identified a substantial overlap, whereby 125 metabolites higher in RS and 103 metabolites higher in FC were shared with cohort 1 (Fig. 1B). Metabolites higher in luminal content (FC, Fig. 1C) were enriched in pathways related to B vitamins, fatty acids, and bile acids, likely connected with microbial metabolism, while metabolites higher in RS, closer to the mucosa, were enriched in pathways related to TCA cycle, amino acids, and cellular membrane, likely reflecting combined host and microbial metabolism (Fig. 1D). We next defined differences within each sampling type between IBD and controls. Comparing 135 IBD vs. 80 control subjects (cohort 1, RS) identified 109 and 85 metabolites higher in controls and IBD, respectively, and comparing 54 IBD vs. 42 controls subjects (cohort 2, FC) identified 75 and 42 metabolites higher in controls and IBD respectively. Several metabolites showed consistent differences between controls and IBD across both RS and FC samples, e.g., higher azelate, ascorbate, and glutarate in controls, and higher cis-7.10.13/16-docosatetraenoic acid, taurine, and palmitoyl carnitine in IBD (Fig. 2A-D). In contrast, some metabolites displayed opposite trends between sample types: cholate, deoxycholate, and 7-ketodeoxycholate were elevated in controls in RS but in IBD in FC (Fig. 2E-F), while quinolinate showed the reverse pattern. Conclusion Metabolomic profiling of luminal (fecal) and mucosal (rectal swab) samples reveals significant niche-related differences, but both niches maintain an IBD-related abnormality. Conflict of interest: Mrs. Naamnh, Raneen: No conflict of interest Levhar, Nina: No conflict of interest Braun, Tzipi: No conflict of interest Efroni, Gilat: No conflict of interest Jessula Levy, David: No conflict of interest Granot, Maya: No conflict of interest Krauthammer, Alexander: No conflict of interest David Berger, Tal: No conflict of interest Loberman-Nachum, Nurit: No conflict of interest Weiss, Batia: No conflict of interest Amir, Amnon: No conflict of interest Haberman Ziv, Yael: Grant: ECCO, CCF, ISF, I-Core, Helmsley, ERC, NIH.
Naamnh et al. (Thu,) studied this question.
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