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

Abstract

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.

Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study

“…Plasma was then aliquoted and stored at −80 • C until the analysis. The analysis of the plasma levels of TRP and its metabolites along the 5-HT and the KYN pathways was conducted within 4 months from the collection, according to the standard methods in our lab at the University of Padova [20,48,49]. The TRP, 5-hydroxytryptophan, 5-HT, and KYN were determined by using an HPLC system equipped with a UV-Vis and fluorometric detectors, whereas the QA, KYNA, 3-HK, and MLT were determined by LC-MS/MS by using alfa-methyltryptophan as an internal standard.…”

“…The TRP, 5-hydroxytryptophan, 5-HT, and KYN were determined by using an HPLC system equipped with a UV-Vis and fluorometric detectors, whereas the QA, KYNA, 3-HK, and MLT were determined by LC-MS/MS by using alfa-methyltryptophan as an internal standard. Details on the methodology can be found in our recent papers [20,48,49].…”

Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?

“…Furthermore, there were no correlations between the KP, cytokines and fatty acids in the study cohort. This implied that the changes of these biological components are independent of each other while being associated with the pathology of the disease [ 170 ].…”

Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia

“…In our view, persistently inflammatory stimuli in these patients may maintain endothelial IDO1 expression and TKP activity, despite the complete viral clearing. The persistent TKP activation may be able to maintain elevated kynurenine blood levels, thus explaining the neurological and immunological dysfunction, as well as the “encephalomyelitis/chronic fatigue syndrome” -like symptoms observed in PACS [ 251 , 252 , 253 ]. The endothelial IDO1-enzyme activity in PACS pneumonia could partly explain respiratory symptoms due to persistent Q/V mismatch as observed in mild COVID-19 pneumonia [ 32 ].…”