ena-STUDY-Microbiota Center Amsterdam-28-03-2018-09:35:23:460-1060
The GRIEG study: Effects of oral vancomycin on the gut microbiome and coagulation parameters in healthy and obese volunteers. The GRIEG study.
Recently, (changes in) the gut microbiome (flora / bacteria) have been associated with obesity and insulin resistance, and other cardiovascular risk factors or atherogenic processes. Venous thrombosis shares these risk factors, probably by a shared low-grade inflammatory profile. This low-grade inflammation may partially be caused by changes in the composition of the gut microbiome or shifts in absolute numbers or abundance of phyli or species of bacteria. This in turn may lead to an increase of gut leakage and to an increased production of lipopolysaccharids (pieces of the outer membrane of gram-negative bacteria) that enter the bloodstream. Consequently a low grade inflammation is present, causing activation of the coagulation system. Changes in the gut microbiome can be caused by dietary influences, antibiotics and probiotics among other (partially unknown) causes. We hypothesize that changes in the microbiome of the gut by application of oral vancomycin might increase systemic metabolic endotoxemia in healthy lean volunteers, consequently creating a pro-coagulant state, marked by increased levels of factor VIII, d-dimer, TF+ monocytes and increased thrombin generation and a reduced fibrinolytic system (expressed as a increased clot lysis time), probably caused by increased levels of plasminogen activator inhibitor (PAI). Also, the classical pathway of the complement system might be more activated after the vancomycin challenge. In obese volunteers, one might speculate that the microbiome will change more towards a normal pattern (more alike to baseline [untreated] values of the lean volunteers) but this might be the other way around according to other literature. However, comparing baseline coagulation parameters of obese with non-obese volunteers, we expect to find that obese volunteers having a pro-coagulant and low-grade inflammatory state, with a changed Firmicutes/Bacteriodetes ratio.
Recently, (changes in) the gut microbiome (flora / bacteria) have been associated with obesity and insulin resistance, and other cardiovascular risk factors or atherogenic processes. Venous thrombosis shares these risk factors, probably by a shared low-grade inflammatory profile. This low-grade inflammation may partially be caused by changes in the composition of the gut microbiome or shifts in absolute numbers or abundance of phyli or species of bacteria. This in turn may lead to an increase of gut leakage and to an increased production of lipopolysaccharids (pieces of the outer membrane of gram-negative bacteria) that enter the bloodstream. Consequently a low grade inflammation is present, causing activation of the coagulation system. Changes in the gut microbiome can be caused by dietary influences, antibiotics and probiotics among other (partially unknown) causes. We hypothesize that changes in the microbiome of the gut by application of oral vancomycin might increase systemic metabolic endotoxemia in healthy lean volunteers, consequently creating a pro-coagulant state, marked by increased levels of factor VIII, d-dimer, TF+ monocytes and increased thrombin generation and a reduced fibrinolytic system (expressed as a increased clot lysis time), probably caused by increased levels of plasminogen activator inhibitor (PAI). Also, the classical pathway of the complement system might be more activated after the vancomycin challenge. In obese volunteers, one might speculate that the microbiome will change more towards a normal pattern (more alike to baseline [untreated] values of the lean volunteers) but this might be the other way around according to other literature. However, comparing baseline coagulation parameters of obese with non-obese volunteers, we expect to find that obese volunteers having a pro-coagulant and low-grade inflammatory state, with a changed Firmicutes/Bacteriodetes ratio.