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

This study has been completed.
Sponsor:
Information provided by:
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01201577
First received: September 13, 2010
Last updated: May 31, 2011
Last verified: May 2011
  Purpose

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.

Condition Intervention Phase
Quorum Sensing
Prebiotics
Probiotics
Sepsis
Dietary Supplement: Bifidobacterium longum BB536
Dietary Supplement: Active hexose correlated compound (AHCC)
Dietary Supplement: Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC)
Dietary Supplement: Corn starch placebo capsule
Drug: Azithromycin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Biological Modulation of Bacterial QSSMs, Innate and Adaptive Immunity by Antibiotics, Probiotics and Prebiotics in Healthy Individuals

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Serum QSSM level [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • T cell Th1/Th2 ratio [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: October 2009
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Placebo/Probiotic Dietary Supplement: Bifidobacterium longum BB536
2 capsules od
Drug: Azithromycin
250mg od
Active Comparator: Placebo/Prebiotic Dietary Supplement: Active hexose correlated compound (AHCC)
One capsule tds
Drug: Azithromycin
250mg od
Active Comparator: Prebiotic/Probiotic Dietary Supplement: Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC)
One capsule tds (prebiotic) and two capsules od (probiotic)
Drug: Azithromycin
250mg od
Placebo Comparator: Placebo/Placebo Dietary Supplement: Corn starch placebo capsule
One capsule tds and two capsules od
Drug: Azithromycin
250mg od

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01201577

Locations
United Kingdom
University of Nottingham
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Dileep Lobob, University of Nottingham
ClinicalTrials.gov Identifier: NCT01201577     History of Changes
Other Study ID Numbers: 09GA014
Study First Received: September 13, 2010
Last Updated: May 31, 2011
Health Authority: United Kingdom: National Institute for Health Research

Keywords provided by University of Nottingham:
Quorum sensing
Prebiotics
Probiotics
Sepsis

Additional relevant MeSH terms:
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Anti-Bacterial Agents
Azithromycin
Antibiotics, Antitubercular
Sulfalene
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on July 20, 2014