Abstract: TH-PO421

Gut Microbiota-Dependent Trimethylamine-N-Oxide and Inflammatory Biomarkers in Patients with Diabetic Nephropathy

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Al-Obaide, Mohammed A., Texas Tech University Health Sciences Center, Amarillo, Texas, United States
  • Singh, Ruchi, Texas Tech University Health Sciences Center, Amarillo, Texas, United States
  • Datta, Palika, Texas Tech University Health Sciences Center, Amarillo, Texas, United States
  • Salguero, Maria Victoria, Texas Tech University Health Sciences Center, Amarillo, Texas, United States
  • Vasylyeva, Tetyana L., Texas Tech University Health Sciences Center, Amarillo, Texas, United States
Background

Trimethylamine N-oxide (TMAO) is a product of diet, gut microbiome, and tissues metabolism. Elevated TMAO levels associated with heart attack, stroke and chronic kidney disease (CKD). We investigated the gut microbiome composition and TMAO levels in the serum of patients with type 2 diabetes mellitus (T2DM) and advanced stages of diabetic nephropathy (DN); and TMAO association with serum IL-6, TNFα, CRP, ET-1, LPS, and zonulin.

Methods

Twenty adult patients with T2DN and CKD 3-4 secondary to DN and 20 healthy subjects (HS) participated in the study. The analysis included: nutrition, metabolic parameters, trimethylamine (TMA) producing gut microbiota, and TMAO, LPS, zonulin and serum biomarkers of inflammation and endothelial dysfunction. The gut microbiota diversity identified by amplified V5-V6 region of the 16S ribosomal RNA (rRNA) genes and DNA sequencing by the MiSeq (Illumina Inc., San Diego, CA) using a 600 cycle v3 sequencing kit. The TMAO quantified by LC/MS method and serum biomarkers by ELISA.

Results

Dietary analysis showed that patients with T2DM and DN consumed less protein and more fat compared to HS and had more than two-fold elevated levels of triglycerides. The gut microbiome in DN patients exhibited a higher abundance of TMA-producing bacteria, p < 0.05. The serum level of TMAO in patients with DN was significantly higher (2.7 ± 0.52 µg/ml) compared to HS (0.43 ± 0.1 µg/ml), p < 0.05. The IL-6 and ET-1 also showed higher levels in the DN patients and positive correlation with TMAO. A positive correlation also observed between zonulin and LPS in both DN and HS groups.

Conclusion

Gut microbiota in patients’ with T2DM-CKD has increased abundance of TMA-producing bacteria, which together with excessive dietary TMAO and increased gut permeability possess substantial risk for cardiovascular health through increased level of chronic inflammation and endothelial dysfunction. The pilot study findings are worth perusing further evaluation.

Funding

  • Clinical Revenue Support