Biological Modulation of Bacterial QSSMs, Innate and Adaptive Immunity by Antibiotics, Probiotics and Prebiotics in Healthy Individuals

May 31, 2011 updated by: University of Nottingham

It has recently been discovered that bacteria are able to communicate using specialised molecules known as Quorum Sensing Signalling Molecules (QSSMs). An accumulation of QSSMs in their surrounding environment allow for the bacteria to quantify the size of colonies. At specific colony sizes the concentration of QSSMs reaches a critical threshold leading to the activation of genes that cause an infection. It is by this mechanism that bacteria within a colony coordinate behaviour to activate infectivity when colony sizes are large enough to withstand defensive measures from the host's immune system. A disruption of quorum sensing may reduce the severity of infection and this has led to the development of inhibitors of quorum sensing as a new strategy in antibacterial therapy.

QSSMs are also thought to facilitate infection by other mechanisms and are able to influence the number and function of a specific type of immune cell known as an 'antigen presenting cell'. These cells are pivotal in allowing the immune system to recognise components of bacteria as foreign and thereby mount the appropriate response. It was found that large numbers of these types of cells underwent programmed cell death (cell suicide) in the presence of QSSMs compared to when QSSMs were absent. This mirrors the situation in blood sampled from patients with severe infections where there is a greater proportion of cell deaths among antigen presenting cells than other types of immune cell.

This study aims to establish in healthy volunteers, the mechanisms by which QSSMs affect immune cells and facilitate the spread of infection. Antibiotic administration in humans can alter the environment of the intestine and can lead to an overgrowth of harmful bacteria to potentially cause an infection. Probiotics supplements can prevent bacterial overgrowth and potentially reduce infective complications. The mechanism, which we aim to clarify, may involve changes in both the production of QSSMs and the function of immune cells.

Hypothesis

  1. Antibiotic use alters gut flora, leading to the appearance in the systemic circulation of bacterial QSSMs and changes in immune function of the host.
  2. Probiotics and/or prebiotics have beneficial effects by preserving the normal resident gut flora, thereby, modulating bacterial QSSMs and preserving the immune function of the host.

Aims

The aims of our study are 2 fold:

  1. Firstly, to study the effect of orally administered antibiotic on QSSMs (in faeces and blood) and on innate and adaptive immunity in healthy humans.
  2. Secondly, to study the effect of orally administered combinations of prebiotic, probiotic and antibiotic on QSSMs (in faeces and blood) and on innate and adaptive immunity in healthy humans.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
        • University of Nottingham

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Male volunteers
  • Age 18-55 years
  • Willing to participate and able to give informed consent
  • Alcohol abstinence during study

Exclusion Criteria:

  • Smokers/substance abusers
  • Individuals with diabetes mellitus
  • Oral/Intravenous steroids
  • Allergy to azithromycin
  • Individuals already taking regular medications/probiotics/nutritional supplements
  • Individuals with chronic disease or currently under investigation
  • Individuals with ≤3 bowel movements/week
  • Individuals with ≥2 bowel movements/day

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Placebo/Probiotic
Dietary supplement: Bifidobacterium longum BB536
2 capsules od
Drug: Azithromycin
250mg od
Active Comparator: Placebo/Prebiotic
Drug: Azithromycin
250mg od
Dietary supplement: Active hexose correlated compound (AHCC)
One capsule tds
Active Comparator: Prebiotic/Probiotic
Drug: Azithromycin
250mg od
Dietary supplement: Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC)
One capsule tds (prebiotic) and two capsules od (probiotic)
Placebo Comparator: Placebo/Placebo
Drug: Azithromycin
250mg od
Dietary supplement: Corn starch placebo capsule
One capsule tds and two capsules od

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Serum QSSM level
Time Frame: 14 days
14 days

Secondary Outcome Measures

Outcome Measure
Time Frame
T cell Th1/Th2 ratio
Time Frame: 14 days
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nottingham

Investigators

  • Principal Investigator: Abeed Chowdhury, MB ChB BSc MRCS, University of Nottingham
  • Study Director: Dileep Lobo, MBBS DM FRCS, University of Nottingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

September 13, 2010

First Submitted That Met QC Criteria

September 13, 2010

First Posted (Estimate)

September 14, 2010

Study Record Updates

Last Update Posted (Estimate)

June 1, 2011

Last Update Submitted That Met QC Criteria

May 31, 2011

Last Verified

May 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09GA014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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