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

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

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.

Study Overview

• Status: Completed
• Conditions: Intestinal Microbiota and Barrier Function
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Bifidobacteria adolescentis BD1; Dietary supplement: Bifidobacteria animalis subsp. lactis BB-12; Dietary supplement: galactooligosaccharide; Dietary supplement: Bifidobacteria adolescentis BD1 and galactooligosaccharide; Dietary supplement: Bifidobacteria animalis subsp. lactis BB-12 and galactooligosaccharide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Collaborators: University of Alberta; University of Nebraska Lincoln
• Investigators: Principal Investigator: Robert Hutkins, PhD, University of Nebraska Lincoln

Publications and helpful links

General Publications

• Krumbeck JA, Rasmussen HE, Hutkins RW, Clarke J, Shawron K, Keshavarzian A, Walter J. Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics. Microbiome. 2018 Jun 28;6(1):121. doi: 10.1186/s40168-018-0494-4.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: February 3, 2015
• First Posted (Estimate): February 4, 2015

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 19, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; DEFB1 protein, human
• Other Study ID Numbers: USDA-NIFA-AFRI-003397