Probiotics and Gut Health

Study Overview
=================
Brief Summary
-----------------
This study evaluates the effects of probiotic consumption on inflammatory outcomes and measures of gut health. Participants will be given yogurt with probiotics for one period and yogurt without probiotics for another, with a break in between. These periods will occur in random order.

Official Title
-----------------
The Role of Probiotics in Attenuating Inflammation and Improving Gut Health in Obese Adults

Conditions
-----------------
Metabolic Syndrome

Intervention / Treatment
-----------------
* Drug: Yogurt smoothie with BB-12
* Drug: Yogurt smoothie


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BMI ≥ to 25 and less than 35 kg/m^2 Increased waist circumference (men: ≥ 94 cm, women: ≥ 80 cm) At least one of the metabolic syndrome criteria- serum triglycerides: ≥ 150 mg/dL HDL cholesterol: ≤ 40 mg/dL in men, ≤ 50 mg/dL in women blood pressure: ≥ 130 mmHg systolic or ≥ 85 mmHg diastolic fasting plasma glucose ≥ 100 mg/dL Exclusion Criteria: allergy to dairy smoking and/or use of tobacco products systolic blood pressure ≥ 160 mmHg diastolic blood pressure > 100 mmHg fasting glucose ≥ 126 mg/dL history of myocardial infarction, cardiovascular disease (CVD), stroke, diabetes mellitus, liver disease, kidney disease, thyroid disease (unless controlled on medication) use of cholesterol or lipid lowering medications use of anti-hypertensive or glucose lowering supplements (psyllium, fish oil capsules, soy lecithin, niacin, fiber, flax, phytoestrogens, and stanol/sterol supplemented foods) refusal to discontinue nutritional supplements, herbs, vitamins, or other probiotics clinical diagnosis of inflammatory bowel disease (IBD) e.g. Chron's disease or ulcerative colitis Use of antibiotics within the last 2 months excessive alcohol consumption (≥ 14 standard drinks per week) regular use of anti-inflammatory medications (e.g. aspirin, ibuprofen)

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Participants will consume one yogurt smoothie daily for the duration of the intervention that contains 3.16 × 109 colony forming units (CFU) bifidobacterium animalis subsp. lactis BB-12. Participants will be asked to refrain from consumption of other yogurt or probiotic-containing foods. | Drug: Yogurt smoothie with BB-12<br>* During the one month intervention period, the participants will consume one yogurt smoothie with BB-12 daily.<br>|
| Placebo Comparator: Control<br>Participants will consume one yogurt smoothie daily for the duration of the intervention that contains no BB-12. Participants will be asked to refrain from consumption of other yogurt or probiotic-containing foods. | Drug: Yogurt smoothie<br>* During the one month control period, the participants will consume one yogurt smoothie daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in inflammatory markers | Change in inflammatory markers in the serum and secreted cytokines from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells compared to baseline. In the serum the markers to be investigated are high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-a), interleukin 1 beta (IL-1B), IL-6, IL-8, IL-10, IL-12p70, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein alpha (MIP-1a), sCD14, and LPS binding protein (LPB). From LPS-stimulated peripheral blood mononuclear cells the cytokines to be investigated are TNF-a, IL-1B, IL-6, IL-8, IL-10, IL-12p70, MCP-1, and MIP-1a. Changes in these inflammatory markers will assist in understanding how the consumption of yogurt containing BB-12 affects the inflammatory status of obese individuals. | At baseline before intervention period 1, at endpoint of intervention period 1 (week 4), at baseline before intervention period 2 (week 8), at endpoint after intervention period 2 (week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in number and activation of leukocytes | Change in quantity and activation of T cells, B cells, dendritic cells, natural killer cells, and monocytes measured by flow cytometry before and after each period. Changes in the number and activation of leukocytes will assist in understanding the impacts of the consumption of yogurt containing BB-12 on leukocytes in obese individuals. | At baseline before intervention period 1, at endpoint of intervention period 1 (week 4), at baseline before intervention period 2 (week 8), at endpoint after intervention period 2 (week 12) | 
| Change in gut permeability | Change in gut permeability, assessed using a lactulose/mannitol gut permeability assay, from baseline. Changes in gut permeability will assist in understanding the impacts of the consumption of yogurt containing BB-12 on gut health and permeability in obese individuals. | At baseline before intervention period 1, at endpoint of intervention period 1 (week 4), at baseline before intervention period 2 (week 8), at endpoint after intervention period 2 (week 12) | 
| Change in gut microbiota populations | Change in gut microbiota populations, assessed with 16s ribosomal ribonucleic acid (rRNA), compared to baseline. Changes in microbial populations will assist in understanding the impacts of the consumption of yogurt containing BB-12 on commensal gut microbiota in obese individuals. | At baseline before intervention period 1, at endpoint of intervention period 1 (week 4), at baseline before intervention period 2 (week 8), at endpoint after intervention period 2 (week 12) | 
| Change in metabolism of gut microbiota populations | Change in the metabolism of gut microbiota populations, measured via transcriptomics, compared to baseline. Changes in the transcriptome of the commensal microbiota will assist in understanding the impacts of the consumption of yogurt containing BB-12 on the metabolism of commensal gut microbiota in obese individuals. | At baseline before intervention period 1, at endpoint of intervention period 1 (week 4), at baseline before intervention period 2 (week 8), at endpoint after intervention period 2 (week 12) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
probiotics, Human, obesity, non-pharmacologic therapy, gut health, microbiome, inflammation