The role of the microbiota in the systemic immune response

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 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. This may attribute to sepsis associated
immunosuppression. Our ultimate aim is to develop new therapeutic strategies to
restore immunity, such as faeces transplantation or administration of selective
components of the microbiota.

To investigate the role of the gut microbiota in the systemic priming of immune
effector cells

Within-subject-controlled intervention study in human volunteers, n=12

Subjects self-administer antibiotics for seven days:
- ciprofloxacin 500mg 2dd1 (Gram negatives and positives)
- vancomycin 250mg 3dd2 (Gram positives)
- metronidazol 500mg 3dd1 (anaerobes)
Blood and feces will be collected before taking antibiotics and 24 hours and 6
weeks after taking antibiotics.

Volunteers may experience side effects when using antibiotics, mostly
gastrointestinal complaints like diarrhoea. Subjects known with any allergic
reaction to any previously administered antibiotic will be excluded from
participation, but novel allergic reactions are possible. The burden also
includes 3 visits - after the initial screening for eligibility visit * to draw
blood and collect faeces (subject himself at home). Subjects are not allowed to
smoke, drink (until 48 hours after the last dose of antibiotics) or travel to
tropical countries.