A Study of a Prebiotic, a Probiotic and a Synbiotic Upon the Gut Microbiota and Immune Response of Healthy Volunteers (XOS)

A Double-blind, Placebo-controlled, Randomized Crossover Study to Determine the Effects of Xylooligosaccharides (XOS), B. Lactis (BI07) and XOS + BI07 Upon the Gut Microbiota and Immune Response of Healthy Volunteers

Healthy volunteers will be recruited to a study where they will be given four different treatments over a 28 week period. These treatments include: a prebiotic, a probiotic, a synbiotic (prebiotic + probiotic) and a placebo. Faecal samples, blood and saliva will be collected and analysed for changes in faecal microbial populations and selected immune responses.

Study Overview

• Status: Completed
• Conditions: Gut Microbiota; Immune Function; Bowel Function; Plasma Lipids
• Intervention / Treatment: Dietary supplement: Prebiotic; Dietary supplement: Bi-07; Dietary supplement: Synbiotic; Dietary supplement: Placebo

Detailed Description

The primary objective of this study is to determine the effect of XOS (administered at 8g/day), B. lactis BI07 (administered at 109 CFU/day) and the synbiotic combination of both (8g/day XOS and 109 CFU/day B. lactis BI07) on the human gut microbiota.

A double-blind, placebo-controlled, randomized crossover study will be conducted in 44 healthy volunteers. The placebo will be maltodextrin (a food grade ingredient, administered at 8g/day).

Changes in the gut microbiota will be determined by measuring bacterial population levels in human faeces using fluorescence in situ hybridisation (FISH) with 16S rRNA targeted oligonucleotide probes. Concentrations of short chain fatty acids (SCFA) will be quantified using gas chromatography (GC).

In addition to analyses performed on the samples at the University of Reading, analyses on microbial metabolites and selected members of the microbiota will also be performed at Danisco Finland, Kantvik. University of Reading will therefore provide Danisco Kantvik with faecal samples of appropriate size.

The secondary objective of this study is to examine the effects of XOS (8g/day), B. lactis BI07 (109 CFU/day) and the synbiotic (8g/day of XOS and 109 CFU/day of B. lactis BI07) on bowel function, immune function and plasma lipids in 44 healthy volunteers. This will be achieved using volunteer diaries of bowel function and mood, and by investigating total plasma lipids, mucosal immunity (salivary and faecal IgA), total leukocyte numbers, expression of cell surface markers on immune cells to identify cell subsets and activation markers, production of inflammatory markers by whole blood cultures, plasma chemokines, phagocytosis and oxidative burst by monocytes and granulocytes, plasma/serum immunoglobulins, acute phase proteins, complement proteins and soluble adhesion molecules.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG6 6AP
      • University of Reading

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• signed consent form
• age 25-65 years
• body mass index 20-30 inclusive
• good general health as determined by medical questionnaires
• additional inclusion criteria: as far as possible, target volunteer group will have mild constipation (bowel movement of less than 1/day, hard stool consistency)

Exclusion Criteria:

• • Evidence of physical or mental disease or planned major surgery, which might limit participation in or completion of the study

  • History of drug abuse, including alcohol
  • Severe allergy or a history of severe abnormal drug reaction
  • Participation in experimental drug trial within four weeks prior to study
  • Participation in prebiotics or laxative trial within the previous three months
  • Use of antibiotics within the previous six months
  • Chronic constipation, diarrhoea or other chronic gastro-intestinal complaint
  • Intake of other prebiotics or probiotics, drugs active on gastrointestinal motility, or a laxative of any class for four weeks prior to study
  • Use of prescribed medication
  • Regular use of aspirin or other anti-inflammatory drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; 8g/day maltodextrin
Experimental: Probiotic	Dietary supplement: Bi-07; 10^9 CFU B. lactis / day
Experimental: Prebiotic	Dietary supplement: Prebiotic; 8g/day xylo-oligosaccharide
Experimental: Synbiotic	Dietary supplement: Synbiotic; 8g/day xylo-oligosaccharide + 10^9 CFU Bi-07

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes to the gut microbiota	Changes in faecal bacterial populations will be assessed through the use of FISH with molecular probes targeting 16S rRNA genes. Genotypic probes targeting the predominant components of the gut microflora (Bacteroides, Bifidobacterium, Clostridium, Lactobacillus, Eubacterium, Atopobacterium, Streptococcus, sulphate reducing bacteria and enterobacteria) and total bacteria will be tagged with fluorescent markers such that quantifiable changes may be determined. Concentrations of short chain fatty acids (SCFA) will be quantified using gas chromatography (GC).	7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bowel function, immune function and plasma lipids	This will be achieved using volunteer diaries of bowel function and mood, and by investigating total plasma lipids, mucosal immunity (salivary and faecal IgA), total leukocyte numbers, expression of cell surface markers on immune cells to identify cell subsets and activation markers, production of inflammatory markers by whole blood cultures, plasma chemokines, phagocytosis and oxidative burst by monocytes and granulocytes, plasma/serum immunoglobulins, acute phase proteins, complement proteins and soluble adhesion molecules.	7 months

Collaborators and Investigators

• Sponsor: University of Reading
• Collaborators: Danisco
• Investigators: Principal Investigator: Glenn R Gibson, BSc, PhD, University of Reading

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: February 29, 2012
• First Submitted That Met QC Criteria: February 29, 2012
• First Posted (Estimate): March 6, 2012

Study Record Updates

• Last Update Posted (Estimate): March 7, 2012
• Last Update Submitted That Met QC Criteria: March 6, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Other Study ID Numbers: 08/38