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Article

Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

1
PCare Laboratory, Fondazione Istituto di Ricerca Pediatrica, Citta’ della Speranza, 35127 Padova, Italy
2
Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy
3
Pediatrician, Via Galvani 6, 35020 Padua, Italy
4
Department of Medicine, University of Padova, 35128 Padova, Italy
5
Department of Laboratory Medicine, Policlinico Azienda Ospedaliera di Padova, 35128 Padova, Italy
6
Independent Statistician, 36020 Solagna, Italy
7
Department of Medicine, University Hospital Santa Maria della Misericordia, University of Udine, 33100 Udine, Italy
8
Department of Medicine, Ospedale Sant’Antonio Abate, Azienda Sanitaria del Friuli Centrale, 33100 Udine, Italy
9
Department of Medicine, Boston Children’s Hospital, Boston, MA 02115, USA
10
Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
11
Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy
12
Department of Psychiatry, McGill University, Montreal, QC H4H 1R3, Canada
13
Division of Neuroscience, IRCSS San Raffaele Scientific Institute, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Masaru Tanaka and Nóra Török
Biomedicines 2021, 9(11), 1724; https://doi.org/10.3390/biomedicines9111724
Received: 16 October 2021 / Revised: 14 November 2021 / Accepted: 15 November 2021 / Published: 19 November 2021
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine. ME/CFS patients were heterogeneous for genetic background, trigger, start mode, symptoms, and evolution. ME/CFS patients had higher levels of IL-17A (p = 0.018), FABP-2 (p = 0.002), and 3-hydroxykynurenine (p = 0.037) and lower levels of kynurenine (p = 0.012) and serotonin (p = 0.045) than controls. Changes in kynurenine and 3-hydroxykynurenine were associated with increased kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine ratios, indirect measures of kynurenine aminotransferases and kynurenine 3-monooxygenase enzymatic activities, respectively. No correlation was found among cytokines, FABP-2, and tryptophan metabolites, suggesting that inflammation, anomalies of the intestinal barrier, and changes of tryptophan metabolism may be independently associated with the pathogenesis of the disease. Interestingly, patients with the start of the disease after infection showed lower levels of kynurenine (p = 0.034) than those not starting after an infection. Changes in tryptophan metabolites and increased IL-17A levels in ME/CFS could both be compatible with anomalies in the sphere of energy metabolism. Overall, clinical traits together with serum biomarkers related to inflammation, intestine function, and tryptophan metabolism deserve to be further considered for the development of personalized medicine strategies for ME/CFS. View Full-Text
Keywords: ME/CFS heterogeneity; cytokines; intestinal permeability; tryptophan metabolism; kynurenine pathway; 3-hydroxykynurenine; kynurenine; serotonin; biomarkers; personalized medicine ME/CFS heterogeneity; cytokines; intestinal permeability; tryptophan metabolism; kynurenine pathway; 3-hydroxykynurenine; kynurenine; serotonin; biomarkers; personalized medicine
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MDPI and ACS Style

Simonato, M.; Dall’Acqua, S.; Zilli, C.; Sut, S.; Tenconi, R.; Gallo, N.; Sfriso, P.; Sartori, L.; Cavallin, F.; Fiocco, U.; Cogo, P.; Agostinis, P.; Aldovini, A.; Bruttomesso, D.; Marcolongo, R.; Comai, S.; Baritussio, A. Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Biomedicines 2021, 9, 1724. https://doi.org/10.3390/biomedicines9111724

AMA Style

Simonato M, Dall’Acqua S, Zilli C, Sut S, Tenconi R, Gallo N, Sfriso P, Sartori L, Cavallin F, Fiocco U, Cogo P, Agostinis P, Aldovini A, Bruttomesso D, Marcolongo R, Comai S, Baritussio A. Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Biomedicines. 2021; 9(11):1724. https://doi.org/10.3390/biomedicines9111724

Chicago/Turabian Style

Simonato, Manuela, Stefano Dall’Acqua, Caterina Zilli, Stefania Sut, Romano Tenconi, Nicoletta Gallo, Paolo Sfriso, Leonardo Sartori, Francesco Cavallin, Ugo Fiocco, Paola Cogo, Paolo Agostinis, Anna Aldovini, Daniela Bruttomesso, Renzo Marcolongo, Stefano Comai, and Aldo Baritussio. 2021. "Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" Biomedicines 9, no. 11: 1724. https://doi.org/10.3390/biomedicines9111724

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