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Identification of Chagas disease biomarkers using untargeted metabolomics
Alfonso Herreros-Cabello1,2, Pau Bosch-Nicolau3,4,5, José A Pérez-Molina4,6
1Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
Insights
This study identifies potential biomarkers for Chagas disease (CD) progression using metabolomics. Novel peptide and amino acid profiles in patient sera could aid in predicting cardiac complications and disease cure.
Area of Science:
- Biochemistry
- Clinical Medicine
- Parasitology
Background:
- Chagas disease (CD) is a neglected tropical disease with significant cardiac morbidity.
- A major clinical challenge is the long latency and lack of biomarkers to predict progression or cure.
- Untargeted metabolomics offers a promising approach for novel biomarker discovery.
Purpose of the Study:
- To identify potential serum biomarkers for Chagas disease progression using untargeted metabolomics.
- To differentiate between indeterminate CD, chronic chagasic cardiomyopathy (CCC), and healthy controls.
- To discover markers that can predict disease progression or treatment outcomes.
Main Methods:
- Cross-sectional analysis of sera from 120 individuals (indeterminate CD, CCC, other cardiomyopathies, healthy controls).
- High-throughput metabolomic profiling of 986 metabolites.
- Statistical analysis to identify distinct metabolic profiles and potential biomarkers.
Main Results:
- Distinct metabolic profiles were identified for cardiomyopathy, indeterminate CD, and healthy groups.
- Increasing trends of phenylacetylglutamine and fibrinopeptide B (1-13) from controls to CCC.
- Decreased bilirubin/biliverdin and increased urobilin correlated with disease progression.
- Elevated cystathionine, phenol glucuronide, and vanillactate distinguished CCC from indeterminate CD and controls.
Conclusions:
- Metabolomics identified potential biomarker candidates for Chagas disease.
- These biomarkers, including peptides and amino acids, may aid in predicting disease progression and cardiac involvement.
- Further validation could translate these findings into clinical practice for Chagas disease management.
Abstract:
Untargeted metabolomic analysis is a powerful tool used for the discovery of novel biomarkers. Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease that affects 6-7 million people with approximately 30% developing cardiac manifestations. The most significant clinical challenge lies in its long latency period after acute infection, and the lack of surrogate markers to predict disease progression or cure. In this cross-sectional study, we analyzed sera from 120 individuals divided into four groups: 31 indeterminate CD, 41 chronic chagasic cardiomyopathy (CCC), 18 Latin Americans with other cardiomyopathies and 30 healthy volunteers. Using a high-throughput panel of 986 metabolites, we identified three distinct profiles among individuals with cardiomyopathy, indeterminate CD and healthy volunteers. After a more stringent analysis, we identified some potential biomarkers. Among peptides, phenylacetylglutamine and fibrinopeptide B (1-13) exhibited an increasing trend from controls to ICD and CCC. Conversely, reduced levels of bilirubin and biliverdin alongside elevated urobilin correlated with disease progression. Finally, elevated levels of cystathionine, phenol glucuronide and vanillactate among amino acids distinguished CCC individuals from ICD and controls. Our novel exploratory study using metabolomics identified potential biomarker candidates, either alone or in combination that if confirmed, can be translated into clinical practice.
