Potential effects of probiotics on atherosclerosis

Abstract

The rising global incidence of atherosclerosis highlights the inadequacies in our understanding of the pathophysiology and treatment of the disease. Increasing evidence outlines the importance of the intestinal microbiome in atherosclerosis, wherein gut-derived uremic toxins (GDUTs) may be of concern. Plasma levels of the GDUTs trimethylamine n-oxide (TMAO), p-cresyl sulfate, and indoxyl sulfate are associated with accelerated renal function decline and increased cardiovascular risk. Thus, reducing the amount of GDUTs in circulation is expected to benefit patients with atherosclerosis. Because some beneficial bacteria can clear GDUTs in vitro and in vivo, orally administered probiotics targeting the intestinal tract represent a promising way to bring about these changes. Atherosclerosis such, this perspective reviews the potential use of probiotics to treat atherosclerosis, particularly in patients with non-traditional risk factors and/or impaired renal function.

Keywords: Probiotics; atherosclerosis; gut microbiota; uremic toxins.

Figure 1

Distribution of the study participants among the clinic population of 3,056 patients in the linear regression model. Measured TPA is plotted against the standardized predicted value of plaque area based on the risk factors in the regression model: age, sex, diabetes, smoking status, serum creatinine, systolic and diastolic blood pressures, total cholesterol, triglycerides, LDL-C, and HDL-C. Control patients are shown as grey dots. The red dots represent study participants with residual scores > 2, i.e., they are the 5% extreme cases with unexplained atherosclerosis, with more plaque than predicted by risk factors by 2 standard deviations or more. Green dots represent protected patients; these are the 5% extremes with much less plaque than predicted, with residual scores < -2; orange dots represent patients with explained atherosclerosis, whose plaque burden is predicted by the risk factors, with residual scores between -2 and 2. Reproduced by permission of Elsevier from^[1]. TPA: Total plaque area; LDL-C: low-density lipoprotein-C; HDL-C: high-density lipoprotein-cholesterol.

Figure 2

Plasma levels of GDUT by quartile of eGFR. Boxplots show plasma levels of GDUT in mmol/L by quartile of eGFR (calculated using the CKD-EPI equations). eGFR quartiles: Q1, ,66 mL/min per 1.73 m²; Q2, 66-78; Q3, 79-90; Q4, $ 91. (A) TMAO; (B) P-cresyl sulfate; (C) hippuric acid; (D) indoxyl sulfate; (E) P-cresyl glucuronide; (F) phenylacetyl glutamine; (G) phenyl sulfate. Plasma levels of all the metabolites were significantly higher in lower quartiles of eGFR; P values were computed for differences in median values by the Kruskal-Wallis test because the distribution of plasma levels was not normally distributed. Reproduced by permission of Elsevier from^[20]. GDUT: Gut-derived uremic toxin; eGFR: estimated glomerular filtration rate; CKD: chronic kidney disease; TMAO: trimethylamine N-oxide.