Biomedical Sciences ETDs

Publication Date

Spring 5-1-2018

Abstract

Background: Acute Coronary Syndrome (ACS) is a leading cause of morbidity and mortality. Metabolic syndrome and obesity are major risk factors for atherosclerosis and ACS. Dysbiosis plays an important role in metabolic syndrome and obesity. Studies show a markedly increased risk of heart attacks in patients with high levels of the pro-atherogenic metabolite trimethylamine-N-Oxide (TMAO). TMAO is produced by the intestinal microbial flora through metabolism of dietary phospholipids; Gram-negative bacteria (Phylum Proteobacteria) is the major source of TMAO metabolism. Patients with obesity and metabolic syndrome have a defective intestinal tight-junctional (TJ) barrier, which allows paracellular permeation of luminal antigens such as lipopolysaccharides (LPS; endotoxins); leading to endotoxemia. Endotoxins are also associated with increased risk of atherosclerosis and cardiovascular disease. We aim to study the hypothesis that patients with ACS have dysbiosis, including higher proportion of Gram-negative bacterial species capable of vi producing the pro-atherogenic metabolite TMAO, and test if dysbiosis in ACS patients is associated with increased intestinal permeability and endotoxemia.

Methods: This is a prospective case-control study conducted at a single university hospital. We enrolled ACS patients (within 72 hours of acute cardiac events) and healthy controls. Relevant clinical and demographic data were collected. Stool microbiome composition was examined using the 16S ribosomal RNA (Illumina) method to identify microbiota taxonomic genera. LPS serum level was measured by an ELISA-based method. The intestinal TJ barrier function was evaluated using lactulose-to-mannitol urinary excretion ratio (L/M ratio). Serum TMAO was measured using a mass spectrometry.

Results: We enrolled 19 patients and 19 controls. ACS patients had increased relative abundance of Gammaproteobacteria and Proteobacteria compared to healthy controls, with mean proportions of 1.8 ± 3.0 vs 0.2 ± 0.4 % (P = .04) and 4.1 ± 3.8 vs 2.1 ± 1.7% (P=.056), respectively. L/M-ratio was three times higher in ACS patients compared to healthy controls (.06 ± .07 vs .023 ± .02, P = .014). There was no difference in the mean serum LPS or TMAO levels.

Conclusion: ACS patients have dysbiosis and increased intestinal permeability. Further studies are required to find the role of dysbiosis in acute cardiac events.

Keywords

Intestinal microbiome, Intestinal permeability, TMAO, Endotoxins, Acute Coronary Syndrome and myocardial infarction.

Sponsors

Clinical and Translational Science Center (CTSC), University of New Mexico

Document Type

Thesis

Language

English

Degree Name

Clinical Research

Level of Degree

Masters

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Thomas Ma, MD, PhD

Second Committee Member

Shiraz Mishra, MBBS, PhD

Third Committee Member

Henry Lin, MD

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