Use of a Novel Synbiotic to Change Human Gut Bacteria and Improve Health in Obese Adults

Study Overview
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Brief Summary
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This study evaluates the effect of a dietary supplement to improve gut health. The participants will take one of six dietary treatments for three weeks, and the gut bacteria and the gut intestinal barrier will be assessed to determine if these dietary treatments beneficially change these markers of gut health.

Detailed Description
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In this study, we intend to test the ecological and therapeutic functionality of a synbiotic combination of a Bifidobacterium adolescentis strain and the prebiotic galactooligosaccharide (GOS) in a human clinical trial. The synbiotic combination was selected based on a novel in vivo selection; specifically, the strain (BD1) is an human autochthonous gut organism that was enriched in an individual by GOS. Our experiments will test the efficacy of this synbiotic compared to a conventional synbiotic. We hypothesize this rationally selected synbiotic will improve intestinal barrier function in obese adult subjects, thereby preventing endotoxemia and metabolic inflammation, physiologically relevant functions that are increased in obese individuals. Our objectives are to: (1) compare the ability of the test and control synbiotic preparations to alter the gut microbiota in obese individuals; (2) test if GOS supports colonization and metabolic activity of test and control strains in the human gut; (3) compare the ability of the two synbiotic preparations to improve intestinal permeability and endotoxemia in obese subjects; and (4) assess associations between the gut microbiota and the test strain with biomarkers for translocation and endotoxemia.

Official Title
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Application of a Novel Synbiotic to Modulate the Human Gut Microbiota and Improve Health

Conditions
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Intestinal Microbiota and Barrier Function

Intervention / Treatment
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* Dietary Supplement: Bifidobacteria adolescentis BD1
* Dietary Supplement: Bifidobacteria animalis subsp. lactis BB-12
* Dietary Supplement: Bifidobacteria adolescentis BD1 and galactooligosaccharide
* Dietary Supplement: Bifidobacteria animalis subsp. lactis BB-12 and galactooligosaccharide
* Dietary Supplement: galactooligosaccharide
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 yrs, obese (30 kg/m2 and greater) Exclusion Criteria: (1) prior intestinal resection, (2) patient history of GI diseases except for hiatal hernia, GERD, hemorrhoids, (3) severe renal disease defined by creatinine more than twice normal, (4) markedly abnormal liver function defined by ALT/AST over 4 times normal levels or elevated bilirubin (5) antibiotic use within the last 12 weeks prior to enrollment, (6) lean or overweight (BMI < 30 kg/m2), (7) intolerant to aspirin, (8) regular use of aspirin, (9) excessive alcohol intake (>2 drinks for men, 1 drink for women daily), (10) presence of uncontrolled chronic metabolic disease (cardiovascular disease, insulin requiring diabetes or uncontrolled diabetes, cancer, etc, (11) a plan to have a major change in dietary habit during the following 6 months, (12) consumption of probiotics, prebiotics or synbiotics without an appropriate 4 week washout period, (13) lactose intolerance or malabsorption; (14) subjects younger than 18 or older than 65, (15) unwillingness to consent to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>5 g lactose given as a placebo | Dietary Supplement: Placebo<br>* lactose powder, 5 grams<br>|
| Experimental: Probiotic 1<br>Bifidobacteria adolescentis BD1, 10^9 | Dietary Supplement: Bifidobacteria adolescentis BD1<br>* packet containing 10^9 cells of Bifidobacteria adolescentis BD1<br>|
| Experimental: Probiotic 2<br>Bifidobacteria animalis subsp. lactis BB-12, 10^9 | Dietary Supplement: Bifidobacteria animalis subsp. lactis BB-12<br>* packet containing 10^9 cells of Bifidobacteria animalis subsp. lactis BB-12<br>|
| Experimental: Prebiotic<br>galactooligosaccaride, 5 g | Dietary Supplement: galactooligosaccharide<br>* 5 g galactooligosaccharide<br>|
| Experimental: Synbiotic 1<br>galacto-oligosaccharide (5 g) and Bifidobacteria adolescentis BD1 (10^9) | Dietary Supplement: Bifidobacteria adolescentis BD1 and galactooligosaccharide<br>* packet containing 10^9 cells Bifidobacteria adolescentis BD1 and 5 g galactooligosaccharide<br>|
| Experimental: Synbiotic 2<br>galacto-oligosaccharide (5 g) and Bifidobacteria animalis subsp. lactis BB-12 (10^9) | Dietary Supplement: Bifidobacteria animalis subsp. lactis BB-12 and galactooligosaccharide<br>* packet containing 10^9 cells B animalis subsp. lactis BB-12 and 5 g galactooligosaccharide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Microbiota, as Measured by Change in Microbiota Composition, Including Presence of B. Adolescentis BD1 and B. Animalis Supsp Lactis BB-12 | change in microbiota composition, including presence of B. adolescentis BD1 and B. animalis supsp lactis BB-12 | baseline and three weeks | 
| Change in Intestinal Permeability as Measured by Change in Percent Sugars in Urine | Change in intestinal permeability as measured by change in percent sugars in urine | baseline and three weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endotoxemia, as Measured by Change in Circulating Endotoxin by Lipopolysaccharide and Lipopolysaccharide-binding Protein | Endotoxemia, as measured by change in circulating endotoxin by lipopolysaccharide and lipopolysaccharide-binding protein | baseline and three weeks |