Sepsis Clinical Trial
Official title:
Biological Modulation of Bacterial QSSMs, Innate and Adaptive Immunity by Antibiotics, Probiotics and Prebiotics in Healthy Individuals
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.
n/a
Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
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