Untargeted Serum Metabolomics of Patients with Immunoglobulin A Nephropathy Using Gas Chromatography-Mass Spectrometry
摘要
The metabolome as a set of metabolites reflects the systemicphysiological state of the organism and is the endpoint of cellularactivity, reflecting the contribution of upstream biological regulatoryprocesses, genome, epigenome, transcriptome, and proteome, as wellas environmental factors, thereby linking genotype to phenotype.For this reason, determining a wide range of small molecules inbiological fluids is becoming an increasingly important approachin studying pathophysiological processes. Due to the unique abilityto access extensive databases of human metabolite mass spectra,gas chromatography-mass spectrometry (GC-MS) is one of the key methodsused in metabolomic analysis. This work presents a pilot untargetedmetabolomics study of blood serum from 10 patients with clinicallyand morphologically confirmed primary immunoglobulin A nephropathy(IgAN) in the active stage and 9 volunteers without signs of kidneypathology. Serum samples were analyzed by GC-MS. Interpretationof mass spectrometry data, annotation and identification of metaboliteswere carried out using the NIST20 library, the HMDB database, andanalytical standards. After performing multi-step data preprocessingand normalization, chemometric analysis was conducted using multivariatestatistical methods. The statistical reliability of the model wasconfirmed by cross-validation. Statistically significant changesin the levels of 20 metabolites were detected in the blood serumof IgAN patients compared to the control group. A decrease in thecontent of a number of amino acids (serine, methionine, tyrosine,tryptophan), as well as the microbial tryptophan metabolite indole-3-propionicacid, was found, along with an increase in the content of some mono-and disaccharides and uric acid, during the active phase of IgAN.The obtained results indicate profound disorders in key metabolicpathways, including energy metabolism, amino acid metabolism, andperoxidation processes, associated with alterations in the intestinalmicrobiome as a probable factor in the development and progressionof the disease.