Metabolite Profiling of the Gut-Renal-Cerebral Axis Reveals a Particular Pattern in Early Diabetic Kidney Disease in T2DM Patients

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6212
• Main Authors: Balint, Lavinia, Socaciu, Carmen, Socaciu, Andreea Iulia, Vlad, Adrian, Gadalean, Florica, Bob, Flaviu, Milas, Oana, Cretu, Octavian Marius, Suteanu-Simulescu, Anca, Glavan, Mihaela, Ienciu, Silvia, Mogos, Maria, Jianu, Dragos Catalin, Petrica, Ligia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.03.2023; MDPI
• Subjects: Accuracy; Acids; Albuminuria - metabolism; Analysis; Biomarkers; blood–brain barrier; Chromatography, High Pressure Liquid - methods; Chronic kidney failure; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; diabetic kidney disease; Diabetic Nephropathies - metabolism; Diabetic nephropathy; Discriminant analysis; Dysbacteriosis; Epidemiology; Growth factors; gut microbiota-derived biomarkers; High performance liquid chromatography; Homeostasis; Humans; Kidney - metabolism; Kidney diseases; Mass spectrometry; Mass spectroscopy; Metabolic pathways; Metabolism; Metabolites; Microbiota; Microvasculature; Multivariate analysis; nitrogen metabolic pathway; Pathogenesis; Permeability; Phenylalanine; podocyte injury; Quadrupoles; Renal function; Retinoic acid; retinoic acid signaling pathway; Serotonin; Signal transduction; Statistical analysis; Subgroups; Sulfates; Tretinoin; Tyrosine; Urine; Romania; diabetic kidney disease; retinoic acid signaling pathway; blood–brain barrier; podocyte injury; gut microbiota-derived biomarkers; nitrogen metabolic pathway; proximal tubule dysfunction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076212

Type 2 diabetes mellitus (T2DM) represents an important microvascular disease concerning the kidney and the brain. Gut dysbiosis and microbiota-derived metabolites may be in relation with early pathophysiological changes in diabetic kidney disease (DKD). The aim of the study was to find new potential gut-derived biomarkers involved in the pathogenesis of early DKD, with a focus on the complex interconnection of these biomarkers with podocyte injury, proximal tubule dysfunction, renal and cerebrovascular endothelial dysfunction. The study design consisted of metabolite profiling of serum and urine of 90 T2DM patients (subgroups P1-normoalbuminuria, P2-microalbuminuria, P3-macroalbuminuria) and 20 healthy controls (group C), based on ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry analysis (UHPLC-QTOF-ESI -MS). By multivariate and univariate analyses of serum and urine, which included Partial Least Squares Discriminant Analysis (PLSDA), Variable Importance Plots (VIP), Random Forest scores, One Way ANOVA and Biomarker analysis, there were discovered metabolites belonging to nitrogen metabolic pathway and retinoic acid signaling pathway which differentiate P1 group from P2, P3, C groups. Tyrosine, phenylalanine, indoxyl sulfate, serotonin sulfate, and retinoic acid express the metabolic fingerprint of P1 group vs. P2, P3, C groups, revealing a particular pattern in early DKD in T2DM patients.