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.
Keywords: Mediterranean diet; TMAO; carotid plaque; intestinal microbiome; metabolites; renal function.