Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection

Gironès, Núria; Carbajosa, Sofía; Guerrero, Néstor; Poveda, Cristina; Chillón-Marinas, Carlos; Fresno, Manuel

doi:10.1371/journal.pntd.0003337

Cited by 59 publications

(77 citation statements)

References 60 publications

(70 reference statements)

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“…Plasma uric acid was decreased in males with CFS (Table 2, Males). Uric acid is the end product of purine metabolism and an important antioxidant molecule (14,15). Plasma adenosine was decreased in females (Table 3, Females).…”

Section: Control Controlmentioning

confidence: 99%

Metabolic features of chronic fatigue syndrome

Naviaux

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

311

335

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More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria. Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls. Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21–67 y). Females were 52 (±2.5) y old (range, 20–67 y). The Karnofsky performance scores were 62 (±3.2) for males and 54 (±3.3) for females. We targeted 612 metabolites in plasma from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites. Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer.

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Section: Control Controlmentioning

confidence: 99%

Metabolic features of chronic fatigue syndrome

Naviaux

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

311

335

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“…Diets regulate the immunometabolic status of the host, which influences the severity of the disease, and thus, the serum metabolic profiling differs between different pathological conditions. Changes in host metabolomic profiling were demonstrated during acute stages of infection in a murine model of T. cruzi infection [19]; however, those observations cannot be extrapolated to evaluate the metabolic changes during the chronic stage of infection (occurring after several weeks in the murine model and after years/decades of infection in human disease), and the disease pathways are different between the acute and the chronic stage of infection. The current study analyzed the serum metabolomic profile of T. cruzi-infected mice fed on different diets that specifically developed RV and LV dilations.…”

Section: Discussionmentioning

confidence: 99%

“…Alterations in the global metabolomic profiling during the acute stage of T. cruzi infection in a murine model have been demonstrated [19]. However, the metabolomic profiles differ between acute and chronic stages of Chagas disease, and the progression to CCM is associated with the chronic phase of infection.…”

Section: Introductionmentioning

confidence: 99%

Diet Alters Serum Metabolomic Profiling in the Mouse Model of Chronic Chagas Cardiomyopathy

Lizardo¹,

Ayyappan²,

Ganapathi³

et al. 2019

Disease Markers

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Chagas disease is caused by Trypanosoma cruzi which is endemic in Latin America. T. cruzi infection results in a latent infection with approximately a third of latently infected patients developing chronic Chagas cardiomyopathy (CCM). CCM is a common cause of cardiomyopathy in endemic regions and has a poor prognosis compared to other cardiomyopathies. The factors responsible for the transition from the asymptomatic indeterminate latent stage of infection to CCM are poorly understood. Our previous studies demonstrated that lipid metabolism and diet are important determinants of disease progression. In the present study, we analyzed various serum metabolomic biomarkers such as acylcarnitines, amino acids, biogenic amines, glycerophospholipids, and sphingolipids in murine models of CCM, where the mice specifically develop either left or right ventricular cardiomyopathy based on the diets fed during the indeterminate stage in a murine model of Chagas disease. Our data provide new insights into the metabolic changes that may predispose patients to CCM and biomarkers that may help predict the risk of developing cardiomyopathy from T. cruzi infection. Author Summary. Chronic Chagas cardiomyopathy (CCM) is a parasitic disease prevalent in Latin America. Currently, no effective drugs or vaccines are available to prevent or cure CCM. The factors involved in the disease severity and progression are poorly understood to design new therapeutic interventions. In order to rapidly identify Chagas patients with a higher risk to develop CCM, a new set of biomarkers specific to Chagas disease is needed. We performed serum metabolomic analyses in chronic T. cruzi-infected mice fed on different diets and identified cardiac ventricular-specific metabolite biomarkers that could define CCM severity. In this paper, we present the results of serum metabolomic analyses and discuss its correlations to the diet-induced metabolic regulations in the pathogenesis of CCM in a murine model of Chagas disease.

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“…In particular, mass spectrometry (MS) methods provide a robust, versatile and sensitive analytical technology allowing high-throughput detection with mass accuracy, precise quantitation and verification of protein variants, splice isoforms, metabolites and disease-specific post-translational modifications (Crutchfield et al, 2016). Indeed, using MS-based approaches, global changes in metabolic profiles in Chagasic patients showing acute myocarditis (Girones et al, 2014) and serological biomarkers showing differences between Chagasic and healthy subjects (Santamaria et al, 2014) were recently identified. In the latter case, biomarker peaks with the best discriminatory power were further characterized by a range of proteomic and immunological techniques, indicating that specific fragments derived from proteolysis of apolipoprotein A-I and one fragment of fibronectin are specifically upregulated in Chagasic patients (Santamaria et al, 2014).…”

Section: Diagnostic Applications For Chagas D Isease: the Road Aheadmentioning

confidence: 99%

Chagas Disease Diagnostic Applications

Balouz

Agüero

Buscaglia

2017

Advances in Parasitology

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Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating illness of major significance throughout Latin America, and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stress the necessity of developing new methods operational in Point-of-Care (PoC) settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery.

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Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection

Cited by 59 publications

References 60 publications

Metabolic features of chronic fatigue syndrome

Metabolic features of chronic fatigue syndrome

Diet Alters Serum Metabolomic Profiling in the Mouse Model of Chronic Chagas Cardiomyopathy

Chagas Disease Diagnostic Applications

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