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Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic
Benjamin C Hofeld1, Venkata K Puppala1, Sudhi Tyagi1
1Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Insights
Lactobacillus plantarum 299v (Lp299v) supplementation reduced inflammation and improved vascular function in coronary artery disease (CAD) patients. Lp299v induced anti-inflammatory gene expression changes in human cells, benefiting CAD patients.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Microbiology
Background:
- Systemic anti-inflammatory therapy benefits coronary artery disease (CAD) patients.
- Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD.
- The anti-inflammatory mechanisms of Lp299v in CAD remain unclear.
Purpose of the Study:
- To investigate if Lp299v's beneficial effects on vascular function in CAD patients are mediated by anti-inflammatory actions.
- To analyze the impact of Lp299v supplementation on the transcriptome of peripheral blood mononuclear cells (PBMCs).
- To correlate Lp299v-induced transcriptome changes with improvements in vascular function.
Main Methods:
- Plasma from CAD patients before and after Lp299v supplementation was incubated with healthy donor PBMCs.
- PBMC transcriptomes were analyzed, and gene ontology analyses were performed.
- Lp299v-induced transcriptome changes were compared with changes in brachial flow-mediated dilation (FMD).
- Daily alcohol users (DAUs) were analyzed separately.
Main Results:
- In non-DAU subjects, Lp299v improved FMD and reduced circulating IL-8, IL-12, and leptin.
- 997 genes in PBMCs showed significant changes post-Lp299v exposure, indicating strong anti-inflammatory effects.
- Pathway analysis revealed downregulation of IL-1β, interferon-stimulated, and toll-like receptor signaling pathways, with increased regulatory T-cell (Treg) activity.
- Gene expression changes, including reduced GBP1, JAK2, and TRAIL, correlated with improved FMD.
Conclusions:
- Lp299v supplementation induces anti-inflammatory transcriptome changes in human PBMCs from non-DAU men with stable CAD.
- These transcriptomic alterations may contribute to the observed improvements in vascular function.
- Further research is needed to identify specific circulating metabolites responsible for these effects.
Abstract:
Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor's PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n = 4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n = 15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01 ± 0.74 vs. 0.22 ± 0.51; P < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1β, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (Treg) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.
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