Acute Probiotic Supplementation and Endothelial Function
Condition: Coronary Artery Disease; Hypertension; Hyperlipidemias; Peripheral Vascular Diseases; Cerebral Arterial Diseases
MeSH terms: Cerebral Arterial Diseases; Coronary Artery Disease; Vascular Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Hyperlipidemias
Study type: Interventional

Summary: 
      One in every two deaths in the United States is caused by cardiovascular disease. Despite
      strong mechanistic links established between a diet rich in lipids and the pathogenesis of
      cardiovascular disease, therapeutic advances have focused on reduction in either ingestion or
      synthesis of cholesterol, and reduction in dietary trans and saturated fatty acids and
      triglycerides. Even in the setting of aggressive high potency statin therapy and global
      cardiovascular risk reduction efforts, most clinical trials reveal a significant residual
      cardiovascular risk with, at best, only 30% reduction in major adverse cardiovascular events.
      There exists a significant unmet clinical need for identifying novel therapies for the
      prevention and treatment of cardiovascular disease. This requires identification of
      additional contributory processes to cardiovascular disease pathogenesis, so that
      mechanism-based interventions may be developed. Endothelial dysfunction is a pathological
      state in which there is systemic inflammation of vascular endothelium with consequent
      expression of pro-vasoconstrictive mediators, thrombotic and atherogenic tendencies.
      Endothelial dysfunction precedes the development of atherosclerosis and portends an increased
      risk of future adverse cardiovascular events. Endothelial dysfunction, therefore, can serve
      as a "barometer" of future cardiovascular risk. Measurement of Flow-mediated dilation ( FMD)
      is widely accepted as a method to assess vascular endothelial function.
    

Detailed description: 
      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, we 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. Our pilot study has
      demonstrated that supplementation of Lactobacillus plantarum 299v (Lp299v) for 6 weeks to
      adults with a history of coronary artery disease showed improvement in endothelial function.
      Whether acute ingestion of a single drink containing Lp299v supplementation favorably impacts
      vascular endothelial function is not known. The study proposed will test the hypothesis that
      supplementation of Lp299v favorably impacts vascular endothelial function after ingestion of
      a single supplement containing Lp299v.

      Specific Aim 1 will determine the acute impact of probiotic supplementation on endothelial
      cell function as measured by brachial artery flow mediated dilation (FMD)

      Specific Aim 2 will determine the impact of acute probiotic supplementation on blood
      biomarkers for inflammation.

      Specific Aim 3 will be to determine the impact of baseline constitution of intestinal
      microbiota (assessed by stool microbiome) on change in FMD as a result of acute response to
      probiotic supplementation.

      Specific Aim 4 will be to determine the impact of baseline constitution of intestinal
      microbiota (assessed by stool microbiome) on change in levels of blood markers for
      inflammation as a result of acute response probiotic supplementation.
    

Intervention name(s): Goodbelly; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Consumption of 1 serving of Goodbelly probiotic daily for 6 weeks. This will be followed by an observation period for 6 weeks during which the subjects will not consume Goodbelly.; To prepare the placebo, the dietitian will first heat a water bath to 80 degrees Celsius. This removes the lactobacillus plantarum 299v from the probiotic drink
Other intervention name(s): Goodbelly probiotic; Goodbelly Probitoic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention