Dried Blood Spot-Based Metabolomic Profiling in Adults with Cystic Fibrosis

Abstract

Mucoviscidosis of the respiratory, gastrointestinal, and genitourinary tracts is the major pathology in patients with cystic fibrosis (CF), a lethal monogenic panethnic and multisystemic disease most commonly identified in Caucasians. Currently, the measurement of immuno reactive trypsinogen in dry blood spots (DBSs) is the gold-standard method for initial newborn screening for CF, followed by targeted CF transmembrane regulator (CFTR) mutation analysis, and ultimate confirmation with abnormally elevated sweat chloride. Previous metabolomics studies in patients with CF reported on different biomarkers such as breath 2-aminoacetophenone produced during acute and chronic infection in human tissues, including the lungs of CF patients. Herein, we used liquid and gas chromatography–mass spectrometry-based targeted metabolomics profiling to identify potentially reliable, sensitive, and specific biomarkers in DBSs collected from 69 young and adult people including CF patients (n = 39) and healthy control (n = 30). A distinctive metabolic profile including 26 significantly differentially expressed metabolites involving amino acids, glycolysis, mitochondrial and peroxisomal metabolism, and sorbitol pathways was identified. Specifically, the osmolyte (sorbitol) was remarkably downregulated in CF patients compared to healthy controls indicating perturbation in the sorbitol pathway, which may be responsible for the mucoviscidosis seen in patients with CF. The significance of our findings is supported by the clinical utility of inhaled mannitol and hypertonic saline in patients with CF. The systemic administration of sorbitol in such patients may confer additional benefits beyond the respiratory system, especially in those with misfolded CFTR proteins.

Metabolomics Profiling of Cystic Renal Disease towards Biomarker Discovery

“…The dysregulation of specific metabolites can signal an altered metabolic pathway, which might have great potential as a therapeutic target. Metabolomics application in real life has been extensively studied for biomarker detection, and early diagnosis, of multiple diseases [ 5 , 20 , 21 ].…”

A Distinctive Human Metabolomics Alteration Associated with Osteopenic and Osteoporotic Patients

“…Metabolomics is a comprehensive analytical approach that allows qualitative and quantitative analysis of alterations in metabolite levels within biological systems in response to specific stimuli and pathogenesis [ 16 , 17 ]. It provides insight into understanding the mechanisms and progressions underlying various physiological and pathological conditions [ 18 ]. Recently, several metabolomics studies have investigated the alterations in the metabolomic profiles associated with BMD.…”

Serum-Based Proteomics Profiling in Adult Patients with Cystic Fibrosis

“…Blood samples were collected from adult patients diagnosed with CF who attended the adult CF-Pulmonology clinic at the King Faisal Specialist Hospital and Research Center (KFSHRC) (Riyadh, KSA). These patients were randomly selected during regular clinic visits and consented to participate in this study according to the Institutional Review Board (IRB) approval [ 34 ]. Detailed genetics and clinical baseline questionnaires were completed for each patient by the treating clinician (IN).…”