Probiotics
Conditions
Brief summary
Probiotics are over-the-counter dietary products with microorganisms that are generally consumed for health benefit. However, the durability of these microorganisms is unclear, particularly when they pass through the highly acidic environment of the stomach. We will test the colonization of these microorganisms among individuals who consume probiotics with and without acid suppression therapy.
Detailed description
All activities will be related to research. Participants will be randomized to receive either over-the-counter acid suppression medication or placebo from weeks -2 through week 4. All participants will receive VSL #3 (over-the-counter probiotic) from weeks 0 through 4. Survey data, serum, and stool samples will be collected at weeks -2, 0, and 4. The intervention medication and probiotics have a very low side effect profile and are available over the counter. All data collection methods are non-invasive. Elucidation of the effects of acid suppression on probiotic colonization will allow us to better understand the utility of probiotics use by individuals on acid suppression medications.
Interventions
DRUGOmeprazole
Proton pump inhibitor (PPI) that suppresses gastric acid secretion
DIETARY_SUPPLEMENTVSL #3
Probiotics
DRUGPlacebo
Placebo to match omeprazole
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers ages 18 years and ≤ 75 years. * Able to visit the study Doctor's office 3 times, answer 3 questionnaires, and provide stools and blood samples.
Exclusion criteria
* Gastric cancer, Barrett's esophagus cancer, any gastrointestinal condition, or soy or gluten sensitivity * Previous abdominal surgery * Currently pregnant or nursing * Had H. Pylori Infection * Diagnosed with any chronic medical condition other than hypertension or hyperlipidemia * Currently consuming herbs or probiotics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Abundance of VSL#3 Probiotic Bacterial Strains When Ingested in the Presence or Absence of the Proton Pump Inhibitor (PPI) Omeprazole at Week 4. | Week 4 | Relative abundance is reported as the percent of combined VSL #3 probiotic bacteria strains in the bacteria sample (S. thermophiles, B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus) following their ingestion in the presence or absence of the gastric acid suppression drug omeprazole. Stool samples were assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Symptoms Related to VSL#3 Treatment. | Week 0 through Week 4 | Participants were asked to report symptoms of gastro-intestinal discomfort experienced within the last 28 days. |
| Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Week 0 and Week 4 | From week 0 to week 4, change in the relative abundance (percentage) of most common types of bacteria phyla normally found in the lower GI track (e.g. Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria) after ingesting VSL#3 in the presence or absence of omeprazole. Stool samples are assessed. |
| Change in Peak Intensity of the Metabolite 1H-Indole-4-carbaldehyde Before and After VSL#3 Probiotic Administration (Omeprazole and VSL #3). | Week 0 and Week 4 | From week 0 to week 4, relative change in metabolites (e.g. short chain fatty acids, bile acid derivatives, flavonoids, amino acids) found in the GI track by mass spectrometry after ingesting VSL#3. Serum samples are assessed. MZ = mass/charge ratio; RT = retention time. MZ/RT data were obtained by mass spectrometry analysis. This is a metabolite of interest for the Omeprazole and VSL#3 group only. |
| Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group). | Week 0 and Week 4 | From week 0 to week 4, relative change in metabolites (e.g. short chain fatty acids, bile acid derivatives, flavonoids, amino acids) found in the GI track by mass spectrometry after ingesting VSL#3. Serum samples are assessed. MZ = mass/charge ratio; RT = retention time. MZ/RT data were obtained by mass spectrometry analysis. These are metabolites of interest for the Placebo and VSL#3 group only. |
Countries
United States
Participant flow
Recruitment details
Participants attended an initial study visit at week -2, followed by a baseline visit at week 0, and a final visit at week 4.
Participants by arm
| Arm | Count |
|---|---|
| Omeprazole and VSL #3 Proton pump inhibitor (Omeprazole) and VSL #3 Probiotics | 15 |
| Placebo and VSL #3 Placebo and VSL #3 Probiotics | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Placebo and VSL #3 | Omeprazole and VSL #3 | Total |
|---|---|---|---|
| Age, Continuous | 37 years STANDARD_DEVIATION 12 | 36 years STANDARD_DEVIATION 13 | 37 years STANDARD_DEVIATION 12 |
| Number of participants experiencing gastro-intestinal symptoms. Bloating | 3 Participants | 1 Participants | 4 Participants |
| Number of participants experiencing gastro-intestinal symptoms. Diarrhea | 0 Participants | 1 Participants | 1 Participants |
| Number of participants experiencing gastro-intestinal symptoms. Flatulence | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic / Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic / White | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized NonHispanic / Asian | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized NonHispanic / Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized NonHispanic / Native Hawaiian / Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized NonHispanic / Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized NonHispanic / White | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment United States | 15 Participants | 15 Participants | 30 Participants |
| Relative Abundance of Probiotic Strains | 0.5875 percentage of abundance STANDARD_DEVIATION 0.5691 | 0.3653 percentage of abundance STANDARD_DEVIATION 0.407 | 0.4764 percentage of abundance STANDARD_DEVIATION 0.4907 |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 20 |
| other Total, other adverse events | 7 / 19 | 9 / 20 |
| serious Total, serious adverse events | 0 / 19 | 0 / 20 |
Outcome results
Primary
Relative Abundance of VSL#3 Probiotic Bacterial Strains When Ingested in the Presence or Absence of the Proton Pump Inhibitor (PPI) Omeprazole at Week 4.
Relative abundance is reported as the percent of combined VSL #3 probiotic bacteria strains in the bacteria sample (S. thermophiles, B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus) following their ingestion in the presence or absence of the gastric acid suppression drug omeprazole. Stool samples were assessed.
Time frame: Week 4
Population: Participants who attended the week 4 visit are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omeprazole and VSL #3 | Relative Abundance of VSL#3 Probiotic Bacterial Strains When Ingested in the Presence or Absence of the Proton Pump Inhibitor (PPI) Omeprazole at Week 4. | 1.002 percentage of abundance | Standard Deviation 0.8403 |
| Placebo and VSL #3 | Relative Abundance of VSL#3 Probiotic Bacterial Strains When Ingested in the Presence or Absence of the Proton Pump Inhibitor (PPI) Omeprazole at Week 4. | 0.8186 percentage of abundance | Standard Deviation 0.5234 |
Comparison: Within group difference between week 0 and week 4 was analyzed.p-value: 0.04ANOVA
Comparison: Within group difference between week 0 and week 4 was analyzed.p-value: >0.99ANOVA
Secondary
Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group).
From week 0 to week 4, relative change in metabolites (e.g. short chain fatty acids, bile acid derivatives, flavonoids, amino acids) found in the GI track by mass spectrometry after ingesting VSL#3. Serum samples are assessed. MZ = mass/charge ratio; RT = retention time. MZ/RT data were obtained by mass spectrometry analysis. These are metabolites of interest for the Placebo and VSL#3 group only.
Time frame: Week 0 and Week 4
Population: Participants in the Placebo and VSL#3 group who attended the week 4 visit are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omeprazole and VSL #3 | Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group). | 11-OXOURSOLIC ACID ACETATE at Week 0 | 95819.8 MZ/RT | Standard Deviation 146506.5 |
| Omeprazole and VSL #3 | Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group). | Iloprost S-isomer at Week 4 | 22405.5 MZ/RT | Standard Deviation 63899.1 |
| Omeprazole and VSL #3 | Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group). | 11-OXOURSOLIC ACID ACETATE at Week 4 | 4726.2 MZ/RT | Standard Deviation 18243.3 |
| Omeprazole and VSL #3 | Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group). | FA(14:0) at Week 0 | 539032.9 MZ/RT | Standard Deviation 519162.2 |
| Omeprazole and VSL #3 | Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group). | FA(14:0) at Week 4 | 249632.3 MZ/RT | Standard Deviation 219622.8 |
| Omeprazole and VSL #3 | Change in Peak Intensity of Metabolites of Interest Before and After VSL#3 Probiotic Administration (Placebo and VSL#3 Group). | Iloprost S-isomer at Week 0 | 87765.6 MZ/RT | Standard Deviation 189360 |
Secondary
Change in Peak Intensity of the Metabolite 1H-Indole-4-carbaldehyde Before and After VSL#3 Probiotic Administration (Omeprazole and VSL #3).
From week 0 to week 4, relative change in metabolites (e.g. short chain fatty acids, bile acid derivatives, flavonoids, amino acids) found in the GI track by mass spectrometry after ingesting VSL#3. Serum samples are assessed. MZ = mass/charge ratio; RT = retention time. MZ/RT data were obtained by mass spectrometry analysis. This is a metabolite of interest for the Omeprazole and VSL#3 group only.
Time frame: Week 0 and Week 4
Population: Participants in the Omeprazole and VSL#3 group who attended the week 4 visit are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omeprazole and VSL #3 | Change in Peak Intensity of the Metabolite 1H-Indole-4-carbaldehyde Before and After VSL#3 Probiotic Administration (Omeprazole and VSL #3). | 1H-Indole-4-carbaldehyde at Week 0 | 80809.5 MZ/RT | Standard Deviation 118044.6 |
| Omeprazole and VSL #3 | Change in Peak Intensity of the Metabolite 1H-Indole-4-carbaldehyde Before and After VSL#3 Probiotic Administration (Omeprazole and VSL #3). | 1H-Indole-4-carbaldehyde at Week 4 | 286707.9 MZ/RT | Standard Deviation 567693.1 |
Secondary
Number of Participants With Symptoms Related to VSL#3 Treatment.
Participants were asked to report symptoms of gastro-intestinal discomfort experienced within the last 28 days.
Time frame: Week 0 through Week 4
Population: Participants who attended the week 4 visit are included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omeprazole and VSL #3 | Number of Participants With Symptoms Related to VSL#3 Treatment. | Bloating | 0 Participants |
| Omeprazole and VSL #3 | Number of Participants With Symptoms Related to VSL#3 Treatment. | Diarrhea | 2 Participants |
| Omeprazole and VSL #3 | Number of Participants With Symptoms Related to VSL#3 Treatment. | Flatulence | 2 Participants |
| Placebo and VSL #3 | Number of Participants With Symptoms Related to VSL#3 Treatment. | Flatulence | 0 Participants |
| Placebo and VSL #3 | Number of Participants With Symptoms Related to VSL#3 Treatment. | Bloating | 2 Participants |
| Placebo and VSL #3 | Number of Participants With Symptoms Related to VSL#3 Treatment. | Diarrhea | 0 Participants |
Secondary
Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration
From week 0 to week 4, change in the relative abundance (percentage) of most common types of bacteria phyla normally found in the lower GI track (e.g. Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria) after ingesting VSL#3 in the presence or absence of omeprazole. Stool samples are assessed.
Time frame: Week 0 and Week 4
Population: Participants who attended the week 4 visit are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omeprazole and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Proteobacteria at Week 4 | 3.12 percentage of abundance | Standard Deviation 3.7 |
| Omeprazole and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Actinobacteria at Week 4 | 3.7 percentage of abundance | Standard Deviation 3.7 |
| Omeprazole and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Proteobacteria at Week 0 | 4.1 percentage of abundance | Standard Deviation 6 |
| Omeprazole and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Bacteroidetes at Week 0 | 66.4 percentage of abundance | Standard Deviation 15.1 |
| Omeprazole and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Firmicutes at Week 4 | 25.7 percentage of abundance | Standard Deviation 12.6 |
| Omeprazole and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Actinobacteria at Week 0 | 2.5 percentage of abundance | Standard Deviation 2.5 |
| Omeprazole and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Bacteroidetes at Week 4 | 66.2 percentage of abundance | Standard Deviation 15 |
| Omeprazole and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Firmicutes at Week 0 | 25.6 percentage of abundance | Standard Deviation 9.6 |
| Placebo and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Actinobacteria at Week 4 | 3.2 percentage of abundance | Standard Deviation 1.9 |
| Placebo and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Firmicutes at Week 0 | 27.2 percentage of abundance | Standard Deviation 9.6 |
| Placebo and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Bacteroidetes at Week 0 | 65.6 percentage of abundance | Standard Deviation 11.3 |
| Placebo and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Bacteroidetes at Week 4 | 68.1 percentage of abundance | Standard Deviation 10.2 |
| Placebo and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Firmicutes at Week 4 | 25.0 percentage of abundance | Standard Deviation 8.3 |
| Placebo and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Proteobacteria at Week 0 | 2.7 percentage of abundance | Standard Deviation 1.8 |
| Placebo and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Proteobacteria at Week 4 | 2.7 percentage of abundance | Standard Deviation 2.4 |
| Placebo and VSL #3 | Relative Abundance (Mean Value) of Most Abundant Bacterial Phylum Before and After VSL#3 Probiotic Administration | Actinobacteria at Week 0 | 3.2 percentage of abundance | Standard Deviation 2.8 |