Inflammatory Response
Conditions
Keywords
prefrail, non-diabetic, metformin, thrombosis, microbiome, cellular respiration, short physical performance batter
Brief summary
Metformin has a well-established safety profile and it has become clear that metformin has additional salutary effects, including anti-inflammatory, anti-aging, and anti-thrombotic properties. In this study, subjects will provide both venous blood samples and stool samples in addition to completing cognitive and physiologic testing at baseline, throughout a 90 day exposure to metformin, and 30 days following exposure to metformin in order to evaluate their immune, microbiome, cellular respiration, thrombotic, and inflammatory responses.
Detailed description
Metformin is considered first-line therapy for patients with type two diabetes with hyperglycemia that cannot be controlled with lifestyle alone. Unlike other oral medications, metformin is favored for its insulin-sensitizing effects resulting in improved glycemic control, weight loss, and overall improvement of metabolic syndrome. Over the past fifteen years, metformin has received significant attention for its other potential therapeutic uses. Metformin has been found to decrease the rate of age-related illness progression improving longevity, especially in the setting of cancer. Recent clinical trials across multiple disease states have shown metformin to decrease all-cause mortality in diabetic and non-diabetic patients. Additionally, in both animal models and human trails, metformin has been shown to decrease the risk of arterial and venous thrombosis without affecting bleeding time through its interaction with platelet mitochondria. Although the mechanisms by which metformin effects longevity is an active area of both basic science and clinical research, it clearly has anti-inflammatory properties which are both independent and dependent of glycemic control. Recently, surgical outcomes have focused on optimizing older, deconditioned patients prior to the operation with varying protocols referred to as prehabilitation. These programs work to improve the body's response to the surgical stress resulting in improved wound healing, decreased postoperative complications, and decreased hospital length of stay. The affect of metformin, like increasing physical activity, has widespread affects on physiology. The investigators, therefore, hypothesize that metformin administration to non-diabetic adults will improve clinical outcomes to physiologic stress by improving underlying immune and inflammatory responses, that can be deleterious. Subjects will have venous samples collected to better understand the cellular response to inflammation, thrombosis, and cellular respiration at baseline, at 4 time points throughout the 90 day exposure to metformin, and 30 days following the completion of exposure to metformin. At the same time points, subjects will have stool samples collected in order to assess changes in their microbiome. Finally, subjects will undergo cognitive testing through the NIH toolbox as well as physiologic testing including (six-minute walk test, grip strength as measured by a dynamometer, and a short physical performance battery) at baseline, after 90 days of exposure, and again 30 days after the completion of exposure.
Interventions
Subjects will be exposed to 500mg, 1000mg, or 1500mg of daily ER Metformin, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure.
DRUGPlacebo
Subjects will be exposed to placebo, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure.
Sponsors
Brian Zuckerbraun
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Subjects will act as their own controls: data will be collect on each subject at baseline, throughout exposure and following, exposure to metformin.
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age ≥55 and ≤85 years of age 2. Non-diabetic 3. Adjusted risk analysis index (RAI) 20-42 4. Estimated glomerular filtration rate \>45 5. No evidence of hepatic dysfunction on comprehensive metabolic panel 6. No clinical evidence of cardiac failure 7. Existing University of Pittsburgh Medical Center Patients
Exclusion criteria
1. Hypersensitivity to metformin or any component of the formulation 2. Acute or chronic metabolic acidosis with or without coma 3. Pregnant or breastfeeding females 4. Evidence or history of hepatic, renal, or cardiopulmonary failure 5. Excessive acute or chronic ethanol use 6. Planned or known hospital admission, exposure to anesthesia, or surgical intervention 30 days prior to study or scheduled 30 days after the trial initiation 7. Laboratory analysis showing HbgA1c \>6.1 or eGFR \<44 on baseline labs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ex Vivo Cytokine Response of Peripheral Blood Mononucleocytes (PBMC) to Inflammatory Stimuli Compared to Baseline, Throughout Exposure, and Following Exposure to Metformin. | Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure) | Venous blood samples will be gathered throughout the study in order to quantify the changes in cytokine expression (FN-γ, IL-10, IL12p40, IL-12p70, IL-1α, IL1β, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNF-α) following ex vivo PBMC exposure to endotoxin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure) | Aggregometry area under the curve with the Y-axis being % aggregometry and the X-axis time in minutes. |
| Measure the Rate of Thrombosis of Peripheral Blood. | Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure) | The endpoints for isolated platelets include platelet activation as measured by FACS for CD62p. |
| Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | Day 0 (baseline), 90, and 120 (30 days post metformin exposure) | The SPPB is a group of measures that combines the results of the gait speed, chair stand and balance tests. The minimum is zero (worse performance) and the maximum is 12 (best performance). |
| Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure) | Bacterial communities using 16S rRNA sequencing in relationship to metformin dosing over time. Species richness or diversity in the sample is measured by Choa1 metric. Chao1 is an estimate of how many species are present in an ecosystem. In general, having more species is considered to be healthier and these values typically range from 100-200 for fecal samples. The Chao1 index over numerous samples across time are explored to understand treatment effects. |
| Mitochondrial Respiration in Both PBMCs and Platelets. | Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure) | Oxidative phosphorylation, respiration, and complex activity will be tested using an Oroboros respirometer. |
| Mitochondrial Content in Both PBMCs and Platelets. | Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure) | Mitochondrial content will be measured by staining for mitotracker, and mitochondrial DNA oxidation will be determined by co-localizing staining for 8-hydroxydeoxyguanosine (8-OHdG). Markers of autophagy will be determined by measuring LC-3 flux, p62, beclin-1, and ATG7 protein levels. |
| Measure Biogenesis of PBMCs. | Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure) | Biogenesis will be determined by measuring RNA for PGC1a, NRF-1, and Tfam. |
| Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | Day 0 (baseline), 90, and 120 (30 days post metformin exposure) | Grip strength over time. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 500mg Exposure Subjects will be exposed to 500mg of daily MetFORMIN Hydrochloride ER for up to 90 days.
MetFORMIN Hydrochloride ER: Subjects will be exposed to 500mg, 1000mg, or 1500mg of daily ER Metformin, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure. | 8 |
| 1000mg Exposure Subjects will be exposed to 1000mg of daily MetFORMIN Hydrochloride ER for up to 90 days.
MetFORMIN Hydrochloride ER: Subjects will be exposed to 500mg, 1000mg, or 1500mg of daily ER Metformin, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure. | 8 |
| 1500mg Exposure Subjects will be exposed to 1500mg of daily MetFORMIN Hydrochloride ER for up to 90 days.
MetFORMIN Hydrochloride ER: Subjects will be exposed to 500mg, 1000mg, or 1500mg of daily ER Metformin, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure. | 8 |
| Placebo Subjects will be exposed to placebo for up to 90 days. | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | 500mg Exposure | Total | Placebo | 1500mg Exposure | 1000mg Exposure |
|---|---|---|---|---|---|
| Age, Continuous | 68 years STANDARD_DEVIATION 6 | 70 years STANDARD_DEVIATION 5.5 | 68 years STANDARD_DEVIATION 6 | 71 years STANDARD_DEVIATION 4 | 70 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 29 Participants | 8 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Female | 5 Participants | 17 Participants | 5 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 15 Participants | 3 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 5 / 8 | 3 / 8 | 6 / 8 | 5 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Ex Vivo Cytokine Response of Peripheral Blood Mononucleocytes (PBMC) to Inflammatory Stimuli Compared to Baseline, Throughout Exposure, and Following Exposure to Metformin.
Venous blood samples will be gathered throughout the study in order to quantify the changes in cytokine expression (FN-γ, IL-10, IL12p40, IL-12p70, IL-1α, IL1β, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNF-α) following ex vivo PBMC exposure to endotoxin.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Population: Samples collected. Results were not yielded as they were not adequate to run samples with the available staffing.
Secondary
Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin.
Grip strength over time.
Time frame: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)
Population: Notably, one patient in the 500mg and 1000mg group was unable to finish the 120d testing secondary to COVID-19 limitations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 500mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 120 days, compared to 0 days | .1 mmHg | Standard Deviation 4.8 |
| 500mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 90 days, compared to 0 days | -5.3 mmHg | Standard Deviation 12.5 |
| 500mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 0 days | 28.2 mmHg | Standard Deviation 10.3 |
| 1000mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 120 days, compared to 0 days | 1.1 mmHg | Standard Deviation 2.7 |
| 1000mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 0 days | 28.9 mmHg | Standard Deviation 8.3 |
| 1000mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 90 days, compared to 0 days | -0.4 mmHg | Standard Deviation 3.1 |
| 1500mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 0 days | 25.7 mmHg | Standard Deviation 7.8 |
| 1500mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 120 days, compared to 0 days | .3 mmHg | Standard Deviation 3 |
| 1500mg Exposure | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 90 days, compared to 0 days | -.2 mmHg | Standard Deviation 2.1 |
| Placebo | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 90 days, compared to 0 days | -.3 mmHg | Standard Deviation 3.5 |
| Placebo | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 120 days, compared to 0 days | -.6 mmHg | Standard Deviation 2 |
| Placebo | Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin. | 0 days | 25.7 mmHg | Standard Deviation 9.2 |
p-value: 0.69ANOVA
Secondary
Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin.
The SPPB is a group of measures that combines the results of the gait speed, chair stand and balance tests. The minimum is zero (worse performance) and the maximum is 12 (best performance).
Time frame: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)
Population: Notably, one patient in the 500mg and 1000mg group was unable to finish the 120d testing secondary to COVID-19 limitations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 500mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 0d | 11.2 Units on a scale | Standard Deviation 0.9 |
| 500mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 120d, change from 0d | 0 Units on a scale | Standard Deviation 0.6 |
| 500mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 90d, change from 0d | -0.3 Units on a scale | Standard Deviation 1.4 |
| 1000mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 0d | 10.8 Units on a scale | Standard Deviation 1.3 |
| 1000mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 120d, change from 0d | 0.2 Units on a scale | Standard Deviation 1 |
| 1000mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 90d, change from 0d | 0.4 Units on a scale | Standard Deviation 0.7 |
| 1500mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 90d, change from 0d | 0.4 Units on a scale | Standard Deviation 0.5 |
| 1500mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 0d | 11.1 Units on a scale | Standard Deviation 0.9 |
| 1500mg Exposure | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 120d, change from 0d | 0.3 Units on a scale | Standard Deviation 1.3 |
| Placebo | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 0d | 10.6 Units on a scale | Standard Deviation 1.3 |
| Placebo | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 120d, change from 0d | 0.5 Units on a scale | Standard Deviation 0.8 |
| Placebo | Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin. | 90d, change from 0d | 1.0 Units on a scale | Standard Deviation 1 |
p-value: <0.001ANOVA
Secondary
Measure Biogenesis of PBMCs.
Biogenesis will be determined by measuring RNA for PGC1a, NRF-1, and Tfam.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Population: Samples were collected. Cell processing did not allow for the analysis of any data from collected samples. No data were therefore able to be collected.
Secondary
Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen.
Aggregometry area under the curve with the Y-axis being % aggregometry and the X-axis time in minutes.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Population: Samples were collected and processed at each time point for each participant. When sample processing did not yeild any result (processing failure) no data could be yeilded and therefore can not be presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 90 days change from day 0 | 1.6 arbitrary units*mins | Standard Deviation 57.6 |
| 500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 120 days change from day 0 | -49.2 arbitrary units*mins | Standard Deviation 84.2 |
| 500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 30 day change from day 0 | -34.7 arbitrary units*mins | Standard Deviation 24.5 |
| 500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 0 days | 56.3 arbitrary units*mins | Standard Deviation 40 |
| 500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 60 days change from day 0 | -28.3 arbitrary units*mins | Standard Deviation 54 |
| 1000mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 30 day change from day 0 | 8.9 arbitrary units*mins | Standard Deviation 50.1 |
| 1000mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 0 days | 67 arbitrary units*mins | Standard Deviation 38 |
| 1000mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 120 days change from day 0 | 1.0 arbitrary units*mins | Standard Deviation 28.9 |
| 1000mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 60 days change from day 0 | -23.5 arbitrary units*mins | Standard Deviation 44.5 |
| 1000mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 90 days change from day 0 | 2.4 arbitrary units*mins | Standard Deviation 84.5 |
| 1500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 60 days change from day 0 | -139.8 arbitrary units*mins | Standard Deviation 376.3 |
| 1500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 90 days change from day 0 | -222.5 arbitrary units*mins | Standard Deviation 456.2 |
| 1500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 30 day change from day 0 | -166.7 arbitrary units*mins | Standard Deviation 409 |
| 1500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 0 days | 196 arbitrary units*mins | Standard Deviation 376 |
| 1500mg Exposure | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 120 days change from day 0 | -196.7 arbitrary units*mins | Standard Deviation 410.6 |
| Placebo | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 120 days change from day 0 | -47.6 arbitrary units*mins | Standard Deviation 103 |
| Placebo | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 90 days change from day 0 | -66.6 arbitrary units*mins | Standard Deviation 102.6 |
| Placebo | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 0 days | 83.3 arbitrary units*mins | Standard Deviation 69 |
| Placebo | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 30 day change from day 0 | -29.6 arbitrary units*mins | Standard Deviation 104.8 |
| Placebo | Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen. | 60 days change from day 0 | -49.4 arbitrary units*mins | Standard Deviation 86.7 |
p-value: 0.6057ANOVA
Secondary
Measure the Rate of Thrombosis of Peripheral Blood.
The endpoints for isolated platelets include platelet activation as measured by FACS for CD62p.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Population: These data were not able to be collected due to storage issues and lab shutdowns during the COVID-19 pandemic.
Secondary
Mitochondrial Content in Both PBMCs and Platelets.
Mitochondrial content will be measured by staining for mitotracker, and mitochondrial DNA oxidation will be determined by co-localizing staining for 8-hydroxydeoxyguanosine (8-OHdG). Markers of autophagy will be determined by measuring LC-3 flux, p62, beclin-1, and ATG7 protein levels.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Population: Samples were collected. Cell processing did not allow for the analysis of any data from collected samples. No data were therefore able to be collected.
Secondary
Mitochondrial Respiration in Both PBMCs and Platelets.
Oxidative phosphorylation, respiration, and complex activity will be tested using an Oroboros respirometer.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Population: Samples were collected. Cell processing did not allow for the analysis of any data from collected samples. No data were therefore able to be collected.
Secondary
Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples.
Bacterial communities using 16S rRNA sequencing in relationship to metformin dosing over time. Species richness or diversity in the sample is measured by Choa1 metric. Chao1 is an estimate of how many species are present in an ecosystem. In general, having more species is considered to be healthier and these values typically range from 100-200 for fecal samples. The Chao1 index over numerous samples across time are explored to understand treatment effects.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 90 | 137.8 Index | Standard Deviation 27.8 |
| 500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 30 | 139.9 Index | Standard Deviation 16.2 |
| 500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 120 | 134 Index | Standard Deviation 23.6 |
| 500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 60 | 121.4 Index | Standard Deviation 20.8 |
| 500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 0 | 136.5 Index | Standard Deviation 19 |
| 1000mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 60 | 137.9 Index | Standard Deviation 17.7 |
| 1000mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 90 | 135 Index | Standard Deviation 18.9 |
| 1000mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 120 | 142.2 Index | Standard Deviation 17.3 |
| 1000mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 30 | 130.7 Index | Standard Deviation 19.4 |
| 1000mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 0 | 107.6 Index | Standard Deviation 13.3 |
| 1500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 60 | 128.6 Index | Standard Deviation 12.7 |
| 1500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 0 | 128.1 Index | Standard Deviation 10.5 |
| 1500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 30 | 128.1 Index | Standard Deviation 13.2 |
| 1500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 90 | 138.2 Index | Standard Deviation 10.3 |
| 1500mg Exposure | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 120 | 144.2 Index | Standard Deviation 16.5 |
| Placebo | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 90 | 152 Index | Standard Deviation 20.5 |
| Placebo | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 30 | 144.75 Index | Standard Deviation 13.2 |
| Placebo | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 0 | 141.5 Index | Standard Deviation 15 |
| Placebo | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 60 | 134.3 Index | Standard Deviation 9.8 |
| Placebo | Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples. | Day 120 | 159.2 Index | Standard Deviation 5.7 |
Comparison: Beta Diversity - Differences between Samples and Sample groupsp-value: <0.01ADONISBeta Diversity