Probiotics and Gut Health (PRO)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Drug: Yogurt smoothie with BB-12; Drug: Yogurt smoothie

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Connie J Rogers, PhD, MPH; Phone Number: 814 867 3716; Email: cjr102@psu.edu

Study Locations

• United States
  • Pennsylvania
    • University Park, Pennsylvania, United States, 16802
      • Recruiting
      • The Pennsylvania State University
      • Contact: Connie J Rogers; Email: cjr102@psu.edu
      • Principal Investigator: Connie J Rogers, PhD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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.

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in trimethylamine N-oxide (TMAO) in serum	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.	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	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.	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)

Collaborators and Investigators

• Sponsor: Penn State University
• Collaborators: United States Department of Agriculture (USDA)

Publications and helpful links

General Publications

• Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008 Jun;57(6):1470-81. doi: 10.2337/db07-1403. Epub 2008 Feb 27.
• Meng H, Ba Z, Lee Y, Peng J, Lin J, Fleming JA, Furumoto EJ, Roberts RF, Kris-Etherton PM, Rogers CJ. Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults. Eur J Nutr. 2017 Mar;56(2):649-661. doi: 10.1007/s00394-015-1109-5. Epub 2015 Nov 30.
• Aggarwal BB. Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Annu Rev Nutr. 2010 Aug 21;30:173-99. doi: 10.1146/annurev.nutr.012809.104755.
• Leber B, Tripolt NJ, Blattl D, Eder M, Wascher TC, Pieber TR, Stauber R, Sourij H, Oettl K, Stadlbauer V. The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study. Eur J Clin Nutr. 2012 Oct;66(10):1110-5. doi: 10.1038/ejcn.2012.103. Epub 2012 Aug 8.
• Sugahara H, Odamaki T, Fukuda S, Kato T, Xiao JZ, Abe F, Kikuchi J, Ohno H. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community. Sci Rep. 2015 Aug 28;5:13548. doi: 10.1038/srep13548.
• Rizzardini G, Eskesen D, Calder PC, Capetti A, Jespersen L, Clerici M. Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12(R) and Lactobacillus paracasei ssp. paracasei, L. casei 431(R) in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br J Nutr. 2012 Mar;107(6):876-84. doi: 10.1017/S000711451100420X. Epub 2011 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2018
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 13, 2017
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): December 14, 2021
• Last Update Submitted That Met QC Criteria: December 12, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: obesity; probiotics; inflammation; Human; microbiome; gut health; non-pharmacologic therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome
• Other Study ID Numbers: STUDY0006843

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No