Can gut-lymph become toxic for mitochondria in sepsis and acute pancreatitis?

Abstract

Acute disease can be caused by a wide range of conditions including sepsis, haemorrhagic shock, burns and acute pancreatitis. But these acute disease patients often exhibit two common features. 1) A similar progression in the order of organ dysfunction, i.e. the lungs proceed the heart, the kidneys then finally the liver. This organ failure defined as multiple organ dysfunction syndrome (MODS) is the major cause of death in these patients. 2) Since the blood is diverted to other vital organs such as heart and brain, the intestine is then damaged due to ischaemic injury. ‘Gutlymph’ hypothesis is currently the most popular hypothesis for the development of MODS. It suggests that the gut-lymph, which bypasses the liver and goes directly to the lungs and the heart and then systemic circulation, is the driving cause for the MODS. In normal condition, gutlymph transports interstitial fluid, lipids and proteins from the intestine to the systemic circulation. In acute diseases, gut-lymph is thought to transport toxic factors from gut to the systemic circulation, thus changing cellular or mitochondrial functions in the target organs to promote MODS. This study aims to investigate the toxic effects of gut-lymph in acute diseases, by investigating the mitochondrial function in heart tissue and peripheral blood mononuclear cells (PBMCs) after the incubation with gut-lymph drained from rodent disease models of sepsis, acute pancreatitis and sham control. Mitochondrial respiration was examined in the target organ and mononuclear cells relative to controls. Activation of complex IV was detected in heart tissues when it was not identified in PBMCs. Further research would be required to improve incubation methods and to find the appropriate concentration of gut-lymph for the mitochondrial study. In addition, the toxic effect of gut-lymph needs to be determined in other target organs and in other cellular functions. Such studies will advance our knowledge on the interactions between gut-lymph and mitochondria in acute diseases and will help to find a way to prevent and treat MODS.