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Page 12 of 18 Stuivenberg et al. Microbiome Res Rep 2025;4:11 https://dx.doi.org/10.20517/mrr.2024.22

which could independently delay the progression of atherosclerosis [88-90] .

Oxidative stress promotes endothelial dysfunction by impairing the vascular endothelium, causing
inflammation, and oxidizing low-density lipoprotein-C (LDL-C) [91-93] . Restoring the endothelial structure
could improve atherosclerosis outcomes, and probiotics have shown some promise in this area. For
instance, probiotic Kefir, a fermented beverage that can be prepared using either milk or water and kefir
grains that are combined with a starter culture that contains a combination of yeast species and lactic acid
bacteria, has been associated with enhanced endothelial function and vascular structure repair in animal
[94]
studies . Furthermore, specific probiotics such as Lactococcus lactis MG5125, Bifidobacterium bifidum
MG731, and Bifidobacterium animalis MG741 have showcased antioxidant properties by bolstering total
antioxidant capacity and mitigating oxidative stress [95-98] . Lactobacillus plantarum NJAU-01 and
Lactobacillus fermentum DR9 have demonstrated the ability to decrease lipid oxidation levels and enhance
antioxidant enzyme activity in rats [99,100] . These discoveries indicate that probiotics have potential as
therapeutic interventions to prevent diseases associated with oxidative stress like atherosclerosis but require
further testing in human cohorts.

Reduced production and sensitivity of NO can also disrupt vascular equilibrium [101-103] . Using probiotics to
enhance NO production and availability may be a new approach to combat atherosclerosis. For instance,
Lactobacillus coryniformis CECT5711 has been shown to inhibit certain inflammatory markers in obese
mice and improve endothelial function by increasing NO levels . Similarly, Lactobacillus casei boosts NO
[104]
production in some human cells . Nevertheless, the impact of probiotics on NO production in vascular
[105]
endothelial cells or animal models has not been tested. Considering that endothelial cells are a primary
source of NO via NO synthase expression, how probiotics regulate NO production in these cells should also
[106]
be inquired . Furthermore, Lactobacillus fermentum CECT5716 has been reported to counteract the
endothelial dysfunction induced by certain medications by reducing oxidative stress and inflammation in
the blood vessels . These findings suggest that probiotics may help alleviate vascular manifestations by
[107]
targeting and suppressing pathways related to oxidative stress.

While all the strains mentioned in this section so far have only been shown to have activity in animal or
cell-based models, clinical studies have also reported that certain probiotics can improve endothelial
dysfunction. In a 12-week trial involving 81 participants, a probiotic that contained Lactobacillus,
Bifidobacterium, and Lactococcus reduced systolic blood pressure, inflammatory markers, and parameters
linked to endothelial dysfunction . However, not all probiotics exhibit these clinical benefits. For example,
[108]
Lactobacillus casei Shirota (LcS) did not show significant improvements in low-grade inflammation or
endothelial dysfunction in patients with metabolic syndrome . These studies highlight the need for further
[109]
research in atherosclerosis patients and with larger sample sizes to better understand the impact of
probiotics on endothelial function.

HOW TO FIND THE RIGHT PROBIOTIC FOR ATHEROSCLEROSIS?
In general, selecting a probiotic strain for a target disease should be based on recommendations from in-
depth reviews or organizations such as the Food and Drug Administration or the European Society for
Paediatric Gastroenterology, Hepatology and Nutrition. In our opinion, the available pool of research seems
insufficient to provide an accurate recommendation for an atherosclerosis-specific probiotic. At present,
there are no probiotic recommendations for atherosclerosis within the Canadian or American websites of
clinically documented probiotic strains and products (www.usprobioticguide.com, accessed on 28 February
2024; www.probioticchart.ca, accessed on 28 February 2024). A major concern we have is that most of the
studies mentioned in this perspective measured the effect of probiotics on factors relevant to atherosclerosis,