Abstract
Trimethylamine-N-oxide (TMAO) is a product of dietary, gut microbiome, and tissues metabolism. Elevated blood TMAO levels are associated with heart attack, stroke and chronic kidney disease (CKD). The purpose of our study was to investigate the gut microbiota associated with trimethylamine (TMA) production, the precursor of TMAO, and the serum levels of TMAO and inflammatory biomarkers associated with type 2 diabetes mellitus (T2DM) and CKD. Twenty adults with T2DM and advanced CKD and 20 healthy adults participated in the study. Analyses included anthropometric and metabolic parameters, characterization of TMA producing gut microbiota, and concentrations of TMAO, lipopolysaccharides (LPS) endotoxin, zonulin (Zo) gut permeability marker, and serum inflammatory and endothelial dysfunction biomarkers. Diversity of the gut microbiota was identified by amplification of V3–V4 regions of the 16S ribosomal RNA genes and DNA sequencing. TMAO was quantified by Mass Spectrometry and serum biomarkers by ELISA. The significance of measurements justified by statistical analysis. The gut microbiome in T2DM-CKD patients exhibited a higher incidence of TMA-producing bacteria than control, p < 0.05. The serum levels of TMAO in T2DM-CKD patients were significantly higher than controls, p < 0.05. TMAO showed a positive correlation with Zo and LPS, inflammatory and endothelial dysfunction biomarkers. A positive correlation was observed between Zo and LPS in T2DM-CKD subjects. An increased abundance of TMA-producing bacteria in the gut microbiota of T2DM-CKD patients together with excessive TMAO and increased gut permeability might impact their risk for cardiovascular disease through elevation of chronic inflammation and endothelial dysfunction.
Highlights
Chronic kidney disease (CKD) affects more than 10% of the global population [1] and approximately 50% of patients with type 2 diabetes mellitus (T2DM) [2]
Significant differences were observed between the healthy subjects (HS) and T2DM-CKD groups for total cholesterol, triglycerides, Low-Density Lipoprotein (LDL), and High-Density Lipoprotein (HDL)
We considered the possible involvement of another important factor in T2DM-CKD, i.e., the gut permeability barrier associated with zonulin
Summary
Chronic kidney disease (CKD) affects more than 10% of the global population [1] and approximately 50% of patients with type 2 diabetes mellitus (T2DM) [2]. Elevated urinary albumin excretion and low glomerular filtration rate are widely accepted as criteria for the diagnosis and clinical grading of diabetic kidney disease [3]. Most of the diabetic patients with CKD have diabetic nephropathy, some cases of glomerulopathy may be due to non-diabetic renal disease [4]. CKD and T2DM often experience increased cardiovascular risk and chronic low-grade inflammation that leads to microvascular deterioration and a progression of vascular complications [5,6,7].
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