P0088The exposome metabolome in paediatric inflammatory bowel disease: A cross-sectional study in a population-based Norwegian cohort

Abstract Background Paediatric inflammatory bowel disease (IBD), comprising the subtypes Crohn’s disease (CD) and ulcerative colitis (UC), is believed to result from an interplay between genetic predisposition and environmental exposures. Examining exposome metabolome may help to identify environmental exposures, including host-derived metabolites, with potential relevance in paediatric IBD. Methods Relative concentrations of metabolites were measured in serum samples from treatment-naïve patients with IBD (N = 80) and symptomatic, non-IBD controls (N = 37) included in the IBSENIII cohort (Table 1). Ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS) was performed. Authentic standards or the Human Metabolome Database were used for annotation. Associations with IBD, with CD (N = 53), and with UC including IBD-unclassified (N = 27), were assessed using logistic regression while adjusting for sex, age, and BMI. In addition, correlations with serum proteins (proximity extension assay technology) were examined. A false discovery rate (PFDR) threshold of 0.1 was applied. Results We observed positive association of aryl sulfate (phenol sulfate; PFDR=0.03) with IBD versus symptomatic controls (Figure 1). Within the IBD population, aryl sulfate was positively correlated with several serum proteins, including CCL20 (r = 0.48, PFDR=0.004), MCP-3 (r = 0.47, PFDR=0.004), and TNF-α (r = 0.45, PFDR=0.001). We observed inverse associations of four perfluoroalkyl substances (PFAS); (linear-perfluorooctane sulfonate (PFOS-L), branched-perfluorohexanesulfonate (PFHxS-B), perfluorooctanoate (PFOA), and branched-perfluorooctane sulfonate (PFOS-B)) with IBD, UC, or both. In IBD, PFOA, PFOS-L, PFHxS-B positively correlated with Delta/Notch-like epidermal growth factor (EGF)-related receptor (DNER) protein levels. The secondary bile acid 6-ketholithocholic acid was inversely associated with UC, while the primary bile acids glycochenodeoxycholic acid-3-O-sulfate, cholic acid and glycocholic acid were positively associated with UC (all PFDR0.1). Conclusion Several metabolites including aryl sulfate were associated with paediatric IBD and correlated with inflammation-related proteins. These findings confirm recent results from preclinical Crohn’s disease1 and may point towards a role of aryl sulfate at IBD diagnosis. Reference: 1.Xue M, Lee SH, Shao J, Leibovitzh H, et al; Crohn’s and Colitis Canada Genetics Environment Microbial Project Research Consortium. Metabolomics reveal distinct molecular pathways associated with future risk of Crohn’s Disease. Gut Microbes. 2025 Dec;17(1):2546998. doi: 10.1080/19490976.2025.2546998. Conflict of interest: Ms. Salomon, Benita: No conflict of interest Salihovic, Samira: No conflict of interest Bache-Wiig Mathisen, Charlotte: No conflict of interest Andersen, Svend: No conflict of interest Olbjørn, Christine: No conflict of interest Perminow, Gøri: No conflict of interest Kristensen, Vendel: Has served as speaker, consultant, and advisory member for or has received investigator-initiatedresearch funding from Takeda, Janssen, Ferring and Tillotts Pharma. Grännö, Olle: No conflict of interest Bergemalm, Daniel: DB has received fees for lectures and/or advisory board from Abbvie, Bristol Mayers Squibb, Johnson and Johnson, Pharmacosmos, Pfizer, Takeda, Tillots Pharma and Sandoz. Kruse, Robert: No conflict of interest Repsilber, Dirk: No conflict of interest Orešič, Matej: No conflict of interest Hyötyläinen, Tuulia: No conflict of interest Høivik, Marte: Investigator-initiated research grants from Takeda, Pfizer,Tillotts, Ferring, and Janssen. Received speaker honorariafrom Takeda, Tillotts, Ferring, AbbVie, Galapagos, and Meda.Advisory board affiliations with Takeda, Galapagos, MSD,Lilly, Celltrion, and AbbVie. Halfvarson, Jonas: Grant support: Swedish Foundation for Strategic Research (RB13-0160 to J.H.), the Swedish Research Council (2020-02021 to J.H.), the Örebro University Hospital research foundation (OLL-890291 to J.H.), NordForsk (90569 to J.H.) and Vinnova (2019-01185 to JH and 2024-01155 co-applicant), IHI, EU, INTERCEPT (Grant agreement number 101194780, co-applicant), miGut-Health, HORIZON-HLTH-2022, EU (Grant Agreement 101095470, Co-applicant), 3TR, IMI 2, EU, (Grant agreement number 831434, Co-applicant), Janssen, MSD, and Takeda. Consulting and/or advisory board fees from: AbbVie, Alfasigma, Aqilion, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead Sciences, Hospira, Index Pharmaceuticals, Janssen, Johnson & Johnson, MEDA, Medivir, Medtronic, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, STADA, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, UCB and speaker’s fees from: AbbVie, Alfasigma, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma and research grant support from Janssen, Merck Sharp & Dohme and Takeda.