Modification of gut barrier dysfunction in sepsis by phosphytidylcholine
Acronym: Phosphatidylcholine
Principal Investigator: Dr. Carsten Schmidt
Team: Dr. Philipp Reuken, Prof. Hortense Slevogt, Ursula Frischmann, Christian Lautenschläger
Research Area: D Sepsis related Organ Failure
Project Number: D2.1
Duration: 01.01.2012 - 31.12.2013
Module: Senior Research Group
The Problem
Gut barrier dysfunction gives rise to bacterial translocation and is one of the main causes of sepsis. We suggest that this barrier defect caused by mucus phosphatidylcholine (PC) deficiency can be reverted at least in part by oral substitution of delayed released PC. The project aims to investigate these prophylactic properties in a mouse model of sepsis.
Results so far
A significant reduction in mortality of sepsis can be reached mainly by prevention of sepsis induction and modulation of septic pathophysiology. Disturbances of microcirculation of the gastrointestinal tract give rise to bacterial translocation and are one of the main causes of sepsis. Recently, we were able to show that probe-based confocal laser endomicroscopy is able to quantify microcirculatory alterations in the gastrointestinal mucosa in a porcine model of septic shock. These results demonstrate a reduced vascularisation of the upper and lower GI-tract, preliminary data in patients suffering from sepsis show analogue results. Pathogenesis and supportive therapeutic implications of these sepsis related aspects are comparable in some aspects to ulcerative colitis, where three independent studies showed clinical response or remission of the disease in about 50% of patients. In prior studies of LPS-induced rodent sepsis an increased degradation of the extracellular protective phospholipid layer has been demonstrated, leading to an increased GI permeability and inflammation. We suggest that this barrier defect caused by mucus phosphatidylcholine deficiency can be reverted at least in part by oral substitution of delayed released PC compared to placebo in a murine sepsis model. Microbial translocation into the systemic circulation and affected organs are supposed to be reduced by PC-pretreatment. Moreover, outcome parameters such as morbidity and mortality as well as histological damage of affected organs will be examined. This concept will be followed by examination of local mucus PC content and hydrophobicity of the mucus (surface tension).
Contact
Tel. +49 (0)3641 - 9 32 46 44
Universitätsklinikum Jena
Klinik für Innere Medizin II
Abteilung Gastroenterologie, Hepatologie, Infektiologie
Erlanger Allee 101
07747 Jena