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Host defenses against metabolic endotoxaemia and their impact on lipopolysaccharide detection

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Pages 125-144 | Received 31 Aug 2016, Accepted 06 Jan 2017, Published online: 01 Mar 2017
 

ABSTRACT

Bacterial endotoxin (lipopolysaccharide, LPS), is one of the most potent inducers of inflammatory signaling, yet it is abundant in the human gut and the modern diet. Small quantities of LPS routinely translocate from the gut lumen to the circulation (so-called metabolic endotoxaemia), and elevated plasma LPS concentrations are reported in a variety of chronic non-communicable diseases, including obesity, non-alcoholic fatty liver disease, atherosclerosis and type II diabetes. Murine models of experimentally-induced endotoxaemia and Toll-like receptor-4 deficiency suggest that endotoxin may promote the metabolic disturbances that underpin these diseases. However, as bioactive LPS is cleared rapidly from the circulation, and reported levels of endotoxin in human plasma vary widely, the potential relevance of metabolic endotoxaemia to human disease remains unclear. We here review insight into these questions gained from human and murine models of experimental endotoxaemia, focusing on the kinetics of LPS neutralization and its clearance from blood, the limitations of the widely used limulus assay and alternative methods for LPS quantitation. We conclude that although new methods for LPS measurement will be required to definitively quantify the extent of metabolic endotoxaemia in man, evidence from numerous approaches suggests that this molecule may play a key role in the development of diverse metabolic diseases.

Acknowledgments

TolaFaraj is supported by a PhD studentship sponsored by the Higher Committee for Education Development in Iraq (D-11-242).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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