Probiotics for Cardiovascular Disease

Overseen By Michael E Widlansky

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must not be taking: Probiotics, Prebiotics, Antibiotics, Warfarin

Disqualifiers: Unstable angina, LV dysfunction, Hypertension, Renal insufficiency, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

215 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers at MCW have discovered a new pathway that links the type of bacteria present in the intestines to the severity of heart attacks. This discovery of a relationship between intestinal bacteria, bacterial metabolites, and severity of heart attacks means that for the first time, the investigators may be able to determine a person's probability of having a heart attack via non-conventional risk factors. This may provide opportunities for novel diagnostic tests as well as a potential for therapeutic intervention. The link between gut microbiota and the severity of heart attacks may also lead to novel therapeutic approaches (probiotics, non-absorbable antibiotics) to prevent heart attacks from happening. The studies proposed will test the hypothesis that altered intestinal microbiota are mechanistically linked to the pathogenesis of cardiovascular disease. The investigator's objective is to determine whether inflammatory markers in the blood are decreased and endothelial cell function improved by a probiotic in patients with established coronary artery disease. Furthermore, the investigators wish to elucidate a mechanism by which the gut microbiota regulates serum inflammatory markers. 1. Specific Aim 1 will determine the impact of a probiotic on circulating leptin and TMAO levels, conventional risk factors for cardiovascular disease and diabetes (total cholesterol, LDL cholesterol, oxidized LDL, triglycerides, C-reactive protein, serum amyloid A, fibrinogen and adiponectin, glucose-dependent- insulinotropic polypeptide (GIP), glucagon-like-peptide (GLP-1), glucagon, insulin), and their relationship to the intestinal microbiota (15 representative microbial groups) as non conventional risk factors. Several blood samples will be collected to measure biomarkers. Participants will provide periodic stool samples in order to measure gut bacterial biodiversity. Lastly, endothelial cell function (flow mediated dilation) will be measured in order to assess blood vessel function. 2. Specific Aim 2 will determine the impact of a probiotic on metabolites derived from the intestinal microbiota as candidates for non-conventional risk factors of cardiovascular disease. The relationship between metabolites derived from the intestinal microbiota, endothelial cell function and risk factors for cardiovascular disease identified in Specific Aim 1 will be correlated.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've had changes in certain heart-related medications in the last 6 weeks or if you're taking specific blood thinners like warfarin.

What data supports the effectiveness of the treatment Goodbelly, which contains Lactobacillus plantarum 299v, for cardiovascular disease?

Research shows that Lactobacillus plantarum, a component of Goodbelly, can reduce inflammation and oxidative stress, which are linked to heart disease. In animal studies, it has been shown to decrease the size of atherosclerotic lesions, suggesting potential benefits for cardiovascular health. ^{1 2 3 4 5}

Is Lactobacillus plantarum safe for human use?

Research shows that Lactobacillus plantarum, a type of probiotic, is generally safe for human use, with studies noting its effects on cholesterol levels and inflammation without significant side effects. ^{1 4 6 7 8}

How does the treatment Goodbelly differ from other treatments for cardiovascular disease?

Goodbelly, containing Lactobacillus plantarum 299v, is unique because it uses probiotics to potentially lower blood glucose and lipids, regulate blood pressure, and reduce cardiovascular disease risk by improving gut health, unlike traditional medications that directly target cholesterol or blood pressure. ^{5 9 10 11 12}

Research Team

Michael E Widlansky

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for adults aged 40-80 with Type II Diabetes and known coronary artery disease, but not severe heart issues or recent heart attacks. Participants should be able to follow the study plan and not have cognitive impairments, uncontrolled high blood pressure, major organ dysfunction, a history of heavy drinking or drug use, or recent probiotic/antibiotic use.

Inclusion Criteria

I have a history of significant heart artery disease.

I have been diagnosed with Type II Diabetes.

I am between 40 and 80 years old.

Exclusion Criteria

My heart's pumping ability is below normal.

My blood pressure is not higher than 170/100 mmHg.

You use alcohol every day or take illegal drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Lactobacillus plantarum 299v or a placebo daily for 6 weeks

6 weeks

Weekly visits for monitoring and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Goodbelly
• Placebo

Trial Overview The trial tests if a probiotic can reduce inflammation markers in the blood and improve blood vessel function in patients with heart disease. It involves taking either the probiotic Goodbelly or a placebo first, providing stool samples for gut bacteria analysis, and undergoing endothelial function tests.

Participant Groups

Group I: Goodbelly First Experimental Treatment 1 Intervention

Subjects in this arm will consume 1 serving of lactobacillus plantarum 299v daily for first 6 weeks.

Group II: Placebo Placebo Group 1 Intervention

Subjects in this arm will consume 1 serving of heat-killed placebo daily for first 6 weeks.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

In a study involving 16 males with cardiovascular disease, consuming the probiotic Lactobacillus plantarum DSM 9843 for four weeks significantly increased intestinal microbial diversity compared to a placebo group.

While the probiotic did not significantly alter most short-chain fatty acids in feces, it did lead to a decrease in isovaleric and valeric acid concentrations, suggesting specific metabolic changes in the gut.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic therapy to men with incipient arteriosclerosis initiates increased bacterial diversity in colon: a randomized controlled trial. Karlsson, C., Ahrné, S., Molin, G., et al.[2010]

In a 6-month clinical trial with 60 patients, the probiotic Bifidobacterium lactis Probio-M8, when combined with standard treatments, significantly improved symptoms of coronary artery disease (CAD) compared to placebo, as measured by the Seattle Angina Questionnaire.

The probiotic group also showed reductions in depression and anxiety, along with lower levels of inflammatory markers and harmful cholesterol, suggesting that probiotics may enhance both cardiovascular and mental health through gut microbiota modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bifidobacterium lactis Probio-M8 Adjuvant Treatment Confers Added Benefits to Patients with Coronary Artery Disease via Target Modulation of the Gut-Heart/-Brain Axes. Sun, B., Ma, T., Li, Y., et al.[2022]

In a rat model of systemic inflammatory response syndrome (SIRS), probiotics Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12) significantly reduced myocardial infarction size, suggesting a protective effect against ischemic-reperfusion injury.

The treatment with these probiotics also normalized various inflammatory and immune parameters, indicating their potential to improve cardiovascular health in the context of metabolic and inflammatory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Probiotic Strains on Myocardial Infarction Size, Biochemical and Immunological Parameters in Rats with Systemic Inflammatory Response Syndrome and Polymorbidity. Borshchev, YY., Sonin, DL., Burovenko, IY., et al.[2023]

In a study involving SPF Wistar rats with antibiotic-induced dysbiosis, treatment with the probiotic Lactobacillus reuteri KR2017 significantly reduced myocardial infarct size after ischemia-reperfusion injury, indicating its potential protective effects on heart tissue.

In contrast, treatment with the yeast Saccharomyces boulardii did not show the same beneficial effects, highlighting the importance of specific probiotic strains in managing heart health during ischemic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Antiobiotic-Induced Disbiosis and Its Correction with Probiotics on Myocardial Tolerance to Ischemia-Reperfusion Injury in SPF Rats. Borshchev, YY., Sinitsa, AV., Zakharchenko, MM., et al.[2022]

Daily consumption of Lactobacillus plantarum ATCC 14917 significantly inhibited the formation of atherosclerotic lesions in atherosclerosis-prone mice, indicating its potential as a therapeutic intervention.

The probiotic treatment reduced levels of pro-inflammatory cytokines and oxidative stress markers while modulating gut microbiota composition, suggesting a mechanism of action that involves alleviating inflammation and oxidative damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-atherosclerotic effects of Lactobacillus plantarum ATCC 14917 in ApoE-/- mice through modulation of proinflammatory cytokines and oxidative stress. Hassan, A., Din, AU., Zhu, Y., et al.[2021]

Lab4 probiotic consortium plus Lactobacillus plantarum CUL66 (Lab4P) significantly reduces atherosclerosis-related parameters in LDL receptor deficient mice fed a high-fat diet for 12 weeks, including lowering LDL/VLDL levels and plaque burden.

Lab4P enhances beneficial HDL levels and alters liver gene expression related to atherosclerosis, suggesting it may stabilize plaques and reduce inflammation, warranting further investigation in human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Lab4P Consortium of Probiotics Attenuates Atherosclerosis in LDL Receptor Deficient Mice Fed a High Fat Diet and Causes Plaque Stabilization by Inhibiting Inflammation and Several Pro-Atherogenic Processes. O'Morain, VL., Chan, YH., Williams, JO., et al.[2022]

In a study involving 49 adults with normal to mildly high cholesterol, the probiotic Lactobacillus plantarum ECGC 13110402 significantly reduced LDL cholesterol by 13.9% in those with baseline total cholesterol under 5mM and by 37.6% in those with baseline cholesterol over 6mM, indicating its potential efficacy in lowering cardiovascular risk.

The probiotic also led to a 6.6% reduction in systolic blood pressure and was well-tolerated with no gastrointestinal side effects reported, suggesting it could be a safe alternative or supplement to traditional cholesterol-lowering treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vivo assessment of the cholesterol-lowering efficacy of Lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults. Costabile, A., Buttarazzi, I., Kolida, S., et al.[2020]

In a study of 100 overweight volunteers, daily intake of heat-killed Lactobacillus plantarum L-137 (HK L-137) for 12 weeks significantly improved inflammation and lipid metabolism, as indicated by better immune cell proliferation and lower liver enzyme levels.

Participants taking HK L-137 showed greater reductions in total cholesterol and low-density lipoprotein cholesterol, especially those with higher initial inflammation levels, suggesting it may be particularly beneficial for individuals at risk of inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial. Tanaka, Y., Hirose, Y., Yamamoto, Y., et al.[2021]

Lactiplantibacillus plantarum (Lb. plantarum) has shown potential in reducing the risk of cardiovascular disease (CVD) by regulating metabolism, lowering blood glucose and lipids, and managing blood pressure.

The review emphasizes the importance of incorporating Lb. plantarum through fermented foods into daily diets, which could help alleviate CVD symptoms and improve overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Mechanisms of the Potential Probiotic Lactiplantibacillus plantarum against Cardiovascular Disease and the Recent Developments in its Fermented Foods. Wang, Z., Wu, J., Tian, Z., et al.[2022]

Treatment with Lactobacillus reuteri CCFM8631 significantly reduced plasma cholesterol levels and liver damage markers in mice on a high-fat diet, suggesting its potential as a preventive measure against atherosclerosis-related cardiovascular disease.

The probiotic also improved gut health by increasing beneficial short-chain fatty acids and altering gut microbiota composition, which may contribute to its cholesterol-lowering effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus reuteri CCFM8631 Alleviates Hypercholesterolaemia Caused by the Paigen Atherogenic Diet by Regulating the Gut Microbiota. Wang, Q., He, Y., Li, X., et al.[2022]

In a 4-week study involving healthy adults aged 18 to 65, supplementation with Bacillus subtilis strain DE111 significantly reduced total cholesterol levels by 8 mg/dl and non-high-density lipoprotein cholesterol by 11 mg/dl, indicating potential cardiovascular benefits.

While Bifidobacterium animalis subsp. lactis did not show significant changes in cardiovascular health measures, the results suggest that B. subtilis may improve cholesterol levels and endothelial function, warranting further research in older adults or those with existing cardiovascular risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus subtilis DE111 intake may improve blood lipids and endothelial function in healthy adults. Trotter, RE., Vazquez, AR., Grubb, DS., et al.[2022]

Two Lactobacillus plantarum strains, S2-5 and S4-1, showed strong probiotic properties, including survival in acidic conditions, tolerance to digestive enzymes, and antimicrobial activity against harmful bacteria.

In an in vivo study, the strain S4-1 significantly reduced serum cholesterol levels in mice when fed fermented milk, highlighting its potential as a beneficial probiotic for cholesterol management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of probiotic properties of Lactobacillus plantarum strains isolated from Chinese sauerkraut. Yu, Z., Zhang, X., Li, S., et al.[2021]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Probiotic therapy to men with incipient arteriosclerosis initiates increased bacterial diversity in colon: a randomized controlled trial. [2010]

2. United States pubmed.ncbi.nlm.nih.gov

Bifidobacterium lactis Probio-M8 Adjuvant Treatment Confers Added Benefits to Patients with Coronary Artery Disease via Target Modulation of the Gut-Heart/-Brain Axes. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The Effect of Probiotic Strains on Myocardial Infarction Size, Biochemical and Immunological Parameters in Rats with Systemic Inflammatory Response Syndrome and Polymorbidity. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of Antiobiotic-Induced Disbiosis and Its Correction with Probiotics on Myocardial Tolerance to Ischemia-Reperfusion Injury in SPF Rats. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Anti-atherosclerotic effects of Lactobacillus plantarum ATCC 14917 in ApoE-/- mice through modulation of proinflammatory cytokines and oxidative stress. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

The Lab4P Consortium of Probiotics Attenuates Atherosclerosis in LDL Receptor Deficient Mice Fed a High Fat Diet and Causes Plaque Stabilization by Inhibiting Inflammation and Several Pro-Atherogenic Processes. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

An in vivo assessment of the cholesterol-lowering efficacy of Lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

The Mechanisms of the Potential Probiotic Lactiplantibacillus plantarum against Cardiovascular Disease and the Recent Developments in its Fermented Foods. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Lactobacillus reuteri CCFM8631 Alleviates Hypercholesterolaemia Caused by the Paigen Atherogenic Diet by Regulating the Gut Microbiota. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Bacillus subtilis DE111 intake may improve blood lipids and endothelial function in healthy adults. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of probiotic properties of Lactobacillus plantarum strains isolated from Chinese sauerkraut. [2021]