1
Schulich School of Medicine and Dentistry M.D. Candidate (CIHR Summer Research Training Program), London, ON N6A 3K7, Canada
2
Division of Neurology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, Canada
3
Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, 1400 Western Road, London, ON N6G 2V4, Canada
4
Current address: Department of Neurology, McMaster University, Hamilton, ON L8S 4K1, Canada
5
Department of Radiology, University of Calgary, Calgary, AB T2N 4N1, Canada
6
Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
7
Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada
8
Departments of Urology and Microbiology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
9
Departments of Physiology & Pharmacology, Schulich School of Medicine and Dentistry Western University, London, ON N6A 3K7, Canada
10
Divisions of Neurology and Clinical Pharmacology, Western University, London, ON N6A 5A5, Canada
Abstract
Metabolic products of the intestinal microbiome such as trimethylamine N-oxide (TMAO) that accumulate in renal failure (gut-derived uremic toxins, GDUTs) affect atherosclerosis and increase cardiovascular risk. We hypothesized that patients on a Mediterranean diet and those consuming lower amounts of dietary precursors would
[...] Read more.
Metabolic products of the intestinal microbiome such as trimethylamine N-oxide (TMAO) that accumulate in renal failure (gut-derived uremic toxins, GDUTs) affect atherosclerosis and increase cardiovascular risk. We hypothesized that patients on a Mediterranean diet and those consuming lower amounts of dietary precursors would have lower levels of GDUTs. Patients attending vascular prevention clinics completed a Harvard Food Frequency Questionnaire (FFQ) and had plasma levels of TMAO, p-cresylsulfate, hippuric acid, indoxyl sulfate, p-cresyl glucuronide, phenyl acetyl glutamine, and phenyl sulfate measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Carotid plaque burden was measured by ultrasound; CKD-Epi equations were used to estimate the glomerular filtration rate. In total, 276 patients completed the study. Even moderate renal function significantly increased plasma GDUTs, which were significantly associated with higher carotid plaque burden. There was no significant difference in plasma levels of any GDUT associated with a Mediterranean diet score or with intake of dietary precursors. In omnivorous patients with vascular disease, the intake of dietary precursors of intestinal metabolites or adherence to a Mediterranean diet did not change plasma GDUT. Approaches other than diet, such as probiotics and repopulation of the intestinal microbiome, may be required to mitigate the adverse effects of GDUTs.
Full article