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Stuivenberg et al. Microbiome Res Rep 2025;4:11 https://dx.doi.org/10.20517/mrr.2024.22 Page 3 of 18

Table 1. Backward linear regression of total plaque area (cube root transform)
Model summary
Model R R square Adjusted R Std. error of the
square estimate
12 0.517 0.267 0.245 2.66330
Coefficients
Model Unstandardized Standardized t Sig.
coefficients coefficients
B Std. error Beta
12 (Constant) 0.047 1.566 0.030 0.976
Age 0.074 0.019 0.239 3.877 < 0.001
Serum high-density lipoprotein -1.169 0.511 -0.155 -2.288 0.023
P-cresyl sulfate 0.017 0.006 0.179 2.809 0.005
Pack-years smoking 0.041 0.009 0.280 4.569 < 0.001
Serum triglycerides -0.497 0.185 -0.183 -2.691 0.008
TMAO 0.069 0.030 0.149 2.307 0.022
2
Dependent variable: cube root transform of TPA mm .
Excluded variables
Model Beta in t Sig. Partial correlation Collinearity statistics
Tolerance
12 Total choline (mg) -0.062 -1.003 0.317 -0.071 0.955
Phenyl sulfate -0.005 -0.085 0.933 -0.006 0.883
Diabetes mellitus -0.005 -0.081 0.936 -0.006 0.873
Hippuric acid 0.027 0.425 0.672 0.030 0.899
Indoxyl sulfate -0.027 -0.295 0.768 -0.021 0.450
Diastolic blood pressure 0.023 0.374 0.709 0.026 0.960
P-cresyl glucuronide -0.001 -0.016 0.988 -0.001 0.600
Phenylacetylglutamine 0.048 0.545 0.587 0.038 0.463
Total choline, no supplements -0.063 -1.016 0.311 -0.071 0.951
(mg)
Systolic blood pressure 0.055 0.889 0.375 0.063 0.956
Sex -0.065 -0.977 0.330 -0.069 0.809

[1]
Reproduced by permission of Elsevier from . TMAO: Trimethylamine n-oxide.

USING PROBIOTICS TO REDUCE GUT MICROBIOTA METABOLITES RELEVANT TO
ATHEROSCLEROSIS
The atherosclerosis-relevant probiotic studies conducted on humans and mice are summarized in Tables 2
and 3, respectively.

TMAO
In the context of atherosclerosis, perhaps the best-known intestinal metabolite is TMAO.
Phosphatidylcholine and carnitine , which have high concentrations in animal-based protein sources,
[14]
[15]
are converted to trimethylamine by gut bacteria, and then oxidized in the liver to TMAO . Among patients
[16]
referred for coronary angiography, TMAO levels in the top quartile were associated with a 2.5-fold increase
[17]
in the risk of myocardial infarction, stroke, or vascular death over 3 years . The harmful effects of TMAO
include thrombogenesis , accelerated renal function decline, and increased mortality . Figure 2 shows
[19]
[18]
that levels of TMAO and other intestinal metabolites are increased with even moderate impairment of renal
function , reaching levels that are normal in older patients. As such, elevated TMAO explains, in part, the
[20]