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Research Innovation\/Medical Research Council","award":["212904\/Z\/18\/Z"],"award-info":[{"award-number":["212904\/Z\/18\/Z"]}]},{"name":"UK Research Innovation\/Medical Research Council","award":["MR\/M016560\/1"],"award-info":[{"award-number":["MR\/M016560\/1"]}]},{"name":"UK Research Innovation\/Medical Research Council","award":["MR\/Y010175"],"award-info":[{"award-number":["MR\/Y010175"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>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\u20130.85], p = 2.34 \u00d7 10\u22124) and serum (0.75 [0.63\u20130.90], p = 1.54 \u00d7 10\u22123. Moreover, suberate (C8-DC) was associated with higher odds of IBS in serum (1.36 [1.15\u20131.61]; p = 1.84 \u00d7 10\u22124) and lower odds of IBS in stool (0.76 [0.63\u20130.91]; p = 2.30 \u00d7 10\u22123). 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/metabo15020121","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T08:05:42Z","timestamp":1739347542000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome"],"prefix":"10.3390","volume":"15","author":[{"given":"Daniel","family":"Kirk","sequence":"first","affiliation":[{"name":"Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-1433","authenticated-orcid":false,"given":"Panayiotis","family":"Louca","sequence":"additional","affiliation":[{"name":"Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Attaye","sequence":"additional","affiliation":[{"name":"Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London SE1 7EH, UK"},{"name":"Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9472-9641","authenticated-orcid":false,"given":"Xinyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari E.","family":"Wong","sequence":"additional","affiliation":[{"name":"Metabolon Inc., Research Triangle Park, Morrisville, NC 27560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3936-4675","authenticated-orcid":false,"given":"Gregory A.","family":"Michelotti","sequence":"additional","affiliation":[{"name":"Metabolon Inc., Research Triangle Park, Morrisville, NC 27560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Falchi","sequence":"additional","affiliation":[{"name":"Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1141-4471","authenticated-orcid":false,"given":"Ana M.","family":"Valdes","sequence":"additional","affiliation":[{"name":"Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London SE1 7EH, UK"},{"name":"Nottingham NIHR Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham NG5 1PB, UK"},{"name":"Inflammation, Recovery and Injury Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M. K.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9790-0571","authenticated-orcid":false,"given":"Cristina","family":"Menni","sequence":"additional","affiliation":[{"name":"Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London SE1 7EH, UK"},{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 Degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41575-020-0286-8","article-title":"Global Burden of Irritable Bowel Syndrome: Trends, Predictions and Risk Factors","volume":"17","author":"Black","year":"2020","journal-title":"Nat. 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