Endotoxemia Clinical Trial
Official title:
The Role of the Gut Microbiota in the Systemic Immune Response During Human Endotoxemia
The purpose of this study is to determine whether treatment with antibiotics, which harm the gut flora, causes the immune system to be less effective.
Rationale: Sepsis ranks among the top ten leading causes of death worldwide. Most
nonsurvivors die in a state of immunosuppression. The gut microbiota exerts numerous
beneficial functions in the host response against infections. Gut flora components express
microorganism-associated molecular patterns (MAMPs) such as lipopolysaccharide (LPS), which
are recognized by pattern recognition receptors (PRRs) expressed by neutrophils and
macrophages. MAMPs from the intestinal microbiota constitutively translocate to the
circulation and prime bone marrow derived neutrophils via PRRs. Antibiotic treatment, which
is standard of care for all patients with sepsis, depletes the gut microbiota and leads to a
diminished release of MAMPs and other bacteria derived products. This causes diminished
priming of systemic immunity, which may attribute to sepsis associated immunosuppression and
an increased susceptibility to invading bacteria.
Objective: To investigate the role of the gut microbiota in the systemic priming of immune
effector cells during human endotoxemia
Study design: Randomized, between- and within-subject-controlled intervention study in human
volunteers
Intervention: All subjects will receive lipopolysaccharide (endotoxin; 2 ng/kg bodyweight)
intravenously to induce experimental endotoxemia. Eight subjects will be pretreated with
broad spectrum antibiotics (ciprofloxacin, vancomycin, metronidazole) for seven days
(washout period of 36 hours before endotoxemia), in order to deplete the gut microbiota.
Blood and faeces will be sampled before, during and after endotoxemia.
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Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
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