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Host defences against metabolic endotoxaemia and their impact on lipopolysaccharide detection

journal contribution
posted on 2023-09-01, 14:03 authored by Tola A. Faraj, Catherine McLaughlin, Clett Erridge
Bacterial endotoxin (lipopolysaccharide, LPS), is one of the most potent inducers of inflammatory signalling, 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, focussing on the kinetics of LPS neutralisation 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.

History

Refereed

  • Yes

Volume

36

Issue number

3

Page range

125-144

Publication title

International Reviews of Immunology

ISSN

1563-5244

Publisher

Taylor & Francis

File version

  • Other

Language

  • eng

Legacy posted date

2017-01-23

Legacy creation date

2017-01-19

Legacy Faculty/School/Department

ARCHIVED Faculty of Science & Technology (until September 2018)

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