Clinical Trial: The Role of the Gut Microbiota in the Systemic Immune Response During Human Endotoxemia
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: The Role of the Gut Microbiota in the Systemic Immune Response During Human Endotoxemia
Brief Summary: 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.
Detailed Summary:
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.
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Current Primary Outcome: Cytokine production in blood [ Time Frame: within 8 hours after LPS administration ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Dates:
Date Received: April 28, 2014
Date Started: June 2014
Date Completion:
Last Updated: December 29, 2015
Last Verified: December 2015
