Biological Modulation of Bacterial QSSMs, Innate and Adaptive Immunity by Antibiotics, Probiotics and Prebiotics in Healthy Individuals
Condition: Quorum Sensing; Prebiotics; Probiotics; Sepsis
MeSH terms: Sepsis
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    


Intervention name(s): Bifidobacterium longum BB536; Active hexose correlated compound (AHCC); Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC); Corn starch placebo capsule; Azithromycin
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Drug
Intervention description(s): 2 capsules od; One capsule tds; One capsule tds (prebiotic) and two capsules od (probiotic); One capsule tds and two capsules od; 250mg od
Intervention MeSH terms: Azithromycin; Sulfalene
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Quorum sensing; Prebiotics; Probiotics; Sepsis