Urine metabolome profiling of immune-mediated inflammatory diseases

BMC Medicine

Research Article

Ana Gutiérrez Casbas¹  Javier P. Gisbert²  Pilar Nos³  Maria Vinaixa⁴  Antoni Beltran⁴  Xavier Correig⁴  Miguel A. Rodríguez⁴  José A. Pinto-Tasende⁵  Juan D. Cañete⁶  Carlos Ferrándiz⁷  Eugeni Domènech⁸  Jesús Tornero⁹  Ricardo Blanco^1,10  Isidoro González-Álvaro^1,11  Lluís Puig^1,12  Arnald Alonso^1,13  Sara Marsal^1,13  Antonio Julià^1,13  Antonio Fernández-Nebro^1,14 

[1] CIBERehd, Madrid, Spain;Hospital General de Alicante, Alicante, Spain;CIBERehd, Madrid, Spain;Hospital Universitario de la Princesa and IIS-IP, Madrid, Spain;CIBERehd, Madrid, Spain;Hospital la Fe, Valencia, Spain;Centre for Omic Sciences, COS-DEEEA-URV-IISPV, Reus, Spain;Metabolomics Platform, CIBERDEM, Reus, Spain;Complejo Hospitalario Juan Canalejo, INIBIC, A Coruña, Spain;Hospital Clínic de Barcelona and IDIBAPS, Barcelona, Spain;Hospital Universitari Germans Trias i Pujol, Badalona, Spain;Hospital Universitari Germans Trias i Pujol, Badalona, Spain;CIBERehd, Madrid, Spain;Hospital Universitario Guadalajara, Guadalajara, Spain;Hospital Universitario Marqués de Valdecilla, Santander, Spain;Hospital Universitario de la Princesa and IIS-IP, Madrid, Spain;Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;Rheumatology Research Group, Vall d’Hebron Hospital Research Institute, Barcelona, Spain;UGC Reumatología, Instituto de Investigación Biomédica (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain;

关键词: Metabolomics;    Urine biomarkers;    Disease activity;    Autoimmune diseases;    Inflammatory diseases;   

DOI  :  10.1186/s12916-016-0681-8

 received in 2016-06-24, accepted in 2016-08-25,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundImmune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn’s disease, and ulcerative colitis.MethodsUsing nuclear magnetic resonance, we analyzed the urine metabolome in a discovery cohort of 1210 patients and 100 controls. Within each IMID, two patient subgroups were recruited representing extreme disease activity (very high vs. very low). Metabolite association analysis with disease diagnosis and disease activity was performed using multivariate linear regression in order to control for the effects of clinical, epidemiological, or technical variability. After multiple test correction, the most significant metabolite biomarkers were validated in an independent cohort of 1200 patients and 200 controls.ResultsIn the discovery cohort, we identified 28 significant associations between urine metabolite levels and disease diagnosis and three significant metabolite associations with disease activity (PFDR < 0.05). Using the validation cohort, we validated 26 of the diagnostic associations and all three metabolite associations with disease activity (PFDR < 0.05). Combining all diagnostic biomarkers using multivariate classifiers we obtained a good disease prediction accuracy in all IMIDs and particularly high in inflammatory bowel diseases. Several of the associated metabolites were found to be commonly altered in multiple IMIDs, some of which can be considered as hub biomarkers. The analysis of the metabolic reactions connecting the IMID-associated metabolites showed an over-representation of citric acid cycle, phenylalanine, and glycine-serine metabolism pathways.ConclusionsThis study shows that urine is a source of biomarkers of clinical utility in IMIDs. We have found that IMIDs show similar metabolic changes, particularly between clinically similar diseases and we have found, for the first time, the presence of hub metabolites. These findings represent an important step in the development of more efficient and less invasive diagnostic and disease monitoring methods in IMIDs.

【 授权许可】

CC BY   
© The Author(s). 2016