PRO: Probiotics and Gut Health

Sponsor

Penn State University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03418857

Collaborator

United States Department of Agriculture (USDA) (U.S. Fed)

Enrollment

Location

Arms

53.1

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metabolic Syndrome	Drug: Yogurt smoothie with BB-12 Drug: Yogurt smoothie	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 29, 2018

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental 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 During the one month intervention period, the participants will consume one yogurt smoothie with BB-12 daily.
Placebo Comparator: Control 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 During the one month control period, the participants will consume one yogurt smoothie daily.

Arm

Intervention/Treatment

Experimental: Experimental

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

During the one month intervention period, the participants will consume one yogurt smoothie with BB-12 daily.

Placebo Comparator: Control

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

During the one month control period, the participants will consume one yogurt smoothie daily.

Outcome Measures

Primary Outcome Measures

Change from baseline in inflammatory markers [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 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.

Secondary Outcome Measures

Change in number and activation of leukocytes [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 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.
Change in gut permeability [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, 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.
Change in gut microbiota populations [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, 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.
Change in metabolism of gut microbiota populations [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 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.

Other Outcome Measures

Change in trimethylamine N-oxide (TMAO) in serum [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 TMAO in serum measured using liquid chromatography with tandem mass spectrometry (LC-MS) compared to baseline. Changes in TMAO, which is associated with gut microbiota, will assist in understanding the mechanism that connects changes in the commensal microbiota in the gut to inflammatory outcomes in obese individuals.
Change in serum metabolomic profile [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 serum metabolomic profile, assessed in hydrophilic and hydrophobic fractions, compared to baseline. Changes in the metabolomic profile will assist in understanding the underlying mechanisms that connect consumption of yogurt containing BB-12 to changes in inflammatory status in obese individuals.

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)