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Article

Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome

1
Department of Twin Research & Genetic Epidemiology, King’s College London, London SE1 7EH, UK
2
Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, 1105 AZ Amsterdam, The Netherlands
3
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands
4
Metabolon Inc., Research Triangle Park, Morrisville, NC 27560, USA
5
Nottingham NIHR Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham NG5 1PB, UK
6
Inflammation, Recovery and Injury Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK
7
Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
Metabolites 2025, 15(2), 121; https://doi.org/10.3390/metabo15020121
Submission received: 15 November 2024 / Revised: 16 January 2025 / Accepted: 17 January 2025 / Published: 12 February 2025
(This article belongs to the Special Issue Advances in Metabolomics and Multi-Omics Integration)

Abstract

Background/Objectives: Irritable bowel syndrome (IBS) is a complex disorder affecting 10% of the global population, but the underlying mechanisms remain poorly understood. By integrating multifluid metabolomics, we aimed to identify metabolite markers of IBS in a large population-based cohort. Methods: We included individuals from TwinsUK with and without IBS, ascertained using the Rome III criteria, and analysed serum (232 cases, 1707 controls), urine (185 cases, 1341 controls), and stool (186 cases, 1284 controls) metabolites (Metabolon Inc.). Results: After adjusting for covariates, and multiple testing, 44 unique metabolites (25 novel) were associated with IBS, including lipids, amino acids, and xenobiotics. Androsterone sulphate, a sulfated steroid hormone precursor, was associated with lower odds of IBS in both urine (0.69 [95% confidence interval = 0.56–0.85], p = 2.34 × 10−4) and serum (0.75 [0.63–0.90], p = 1.54 × 10−3. Moreover, suberate (C8-DC) was associated with higher odds of IBS in serum (1.36 [1.15–1.61]; p = 1.84 × 10−4) and lower odds of IBS in stool (0.76 [0.63–0.91]; p = 2.30 × 10−3). On the contrary, 32 metabolites appeared to be fluid-specific, including indole, 13-HODE + 9-HODE, pterin, bilirubin (E,Z or Z,Z), and urolithin. The remaining 10 metabolites were associated with IBS in one fluid with suggestive evidence (p < 0.05) in another fluid. Finally, we identified androgenic signalling, dicarboxylates, haemoglobin, and porphyrin metabolism to be significantly over-represented in individuals with IBS compared to controls. Conclusions: Our results highlight the utility of a multi-fluid approach in IBS research, revealing distinct metabolic signatures across biofluids.
Keywords: irritable bowel syndrome; serum; stool; urine metabolomics irritable bowel syndrome; serum; stool; urine metabolomics

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MDPI and ACS Style

Kirk, D.; Louca, P.; Attaye, I.; Zhang, X.; Wong, K.E.; Michelotti, G.A.; Falchi, M.; Valdes, A.M.; Williams, F.M.K.; Menni, C. Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome. Metabolites 2025, 15, 121. https://doi.org/10.3390/metabo15020121

AMA Style

Kirk D, Louca P, Attaye I, Zhang X, Wong KE, Michelotti GA, Falchi M, Valdes AM, Williams FMK, Menni C. Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome. Metabolites. 2025; 15(2):121. https://doi.org/10.3390/metabo15020121

Chicago/Turabian Style

Kirk, Daniel, Panayiotis Louca, Ilias Attaye, Xinyuan Zhang, Kari E. Wong, Gregory A. Michelotti, Mario Falchi, Ana M. Valdes, Frances M. K. Williams, and Cristina Menni. 2025. "Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome" Metabolites 15, no. 2: 121. https://doi.org/10.3390/metabo15020121

APA Style

Kirk, D., Louca, P., Attaye, I., Zhang, X., Wong, K. E., Michelotti, G. A., Falchi, M., Valdes, A. M., Williams, F. M. K., & Menni, C. (2025). Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome. Metabolites, 15(2), 121. https://doi.org/10.3390/metabo15020121

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