title: Global metabolomic profiling of acute myocarditis caused by Trypanosoma cruzi infection.
abstract: Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain; Instituto de Investigación Sanitaria de la Princesa, Madrid, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Gironès
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Carbajosa
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors.forename: Néstor A
authors.initials: NA
authors.lastname: Guerrero
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Poveda
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Chillón-Marinas
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain; Instituto de Investigación Sanitaria de la Princesa, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000150:complications* / Q000378:metabolism*; D003408:Cresols / Q000378:metabolism; D005260:Female; D053858:Metabolic Networks and Pathways / Q000502:physiology; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000209:etiology* / Q000378:metabolism*; D013463:Sulfuric Acid Esters / Q000378:metabolism; D014349:Trypanosoma cruzi
chemical_list: D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate