Abstract
Objective: Endotoxin, also known as lipopolysaccharide (LPS), is a potent immune stimulant. Low levels of endotoxin exposure (metabolic endotoxemia) play a pivotal role in metabolic disorders. However, there is no robust clinical assay to directly quantify metabolic endotoxemia. We aimed to validate the whole blood Endotoxin Activity Assay (EAA™) as a novel, rapid method to quantify low grade metabolic endotoxemia against the well-established lipopolysaccharide binging protein assay (LBP), a robust surrogate marker of endotoxaemia. Methods: 67 women and 47 men aged 21 to 47 years (35.4 ± 5.5 years, 34.5 ± 7.2 years respectively) were assessed for adiposity (BMI, waist circumference and % body fat using bio-impedance), endotoxin levels (LBP, EAA™) and inflammatory status (serum CRP, IL-6, IL-8). Results: There was no direct relationship between EAA™ and LBP measures for quantitating metabolic endotoxemia for either women or men (R=0.146, p=0.284; R=0.283 p=0.09 respectively). In women, the traditional indirect marker of endotoxemia LBP correlated significantly with CRP and IL-6, measures of generalised immune activation and inflammation (R=0.664, p<0.001, R=0.296, p=0.028 respectively), but not with EAA™ assed endotoxemia. Supporting this relationship, LBP correlated with BMI and body fat percentage (R=0.306, p=0.022; R=0.301, p=0.024 respectively). However, the EAA™ only correlated with body fat percentage (R=0.382, p=0.014). In men, LBP was significantly related to CRP and IL-6 (R=0.345, p=0.046; R=0.421, p=0.009 respectively), but no relationship was observed between these inflammatory markers and EAA™ assed metabolic endotoxemia (R=0.206, p=0.243; R=0.280, p=0.093 respectively). There was no relationship between EAA™ or LBP and any of the three measures of adiposity. Conclusion: In conclusion, the existing rapid whole blood EAA™ method of analysis was not suitable to detect low levels of endotoxemia known to be present in the obese state, while the results suggest LBP indirect analysis remains the superior tool for measuring low grade endotoxemia in this population.
Highlights
Endotoxins, known as lipopolysaccharides (LPS), are fragments derived from the outer membrane of gram negative bacteria [1]
Lipopolysaccharide binding protein assay (LBP) was significantly related to C-reactive protein (CRP) and Interleukin 6 (IL-6) (R=0.345, p=0.046; R=0.421, p=0.009 respectively), but no relationship was observed between these inflammatory markers and Endotoxin Activity Assay (EAATM) assed metabolic endotoxemia (R=0.206, p=0.243; R=0.280, p=0.093 respectively)
In conclusion, the existing rapid whole blood EAATM method of analysis was not suitable to detect low levels of endotoxemia known to be present in the obese state, while the results suggest LBP indirect analysis remains the superior tool for measuring low grade endotoxemia in this population
Summary
Endotoxins, known as lipopolysaccharides (LPS), are fragments derived from the outer membrane of gram negative bacteria [1]. Despite significant research interest on the effect of low levels of endotoxin exposure on health [2], there is no robust gold standard assay to directly test for metabolic endotoxemia, thereby limiting research advances in the field. The LBP is reported to be an easy to conduct and robust indirect measurement of endotoxin exposure, with this acute-phase reactant protein being produced, predominantly by the liver [3] in response to endotoxin exposure. The LBP has been used extensively to detect low levels of metabolic endotoxemia associated with obesity [5,6,7,8,9]. LBP has been used to detect varying levels of endotoxemia in inflammatory bowel conditions, pancreatitis, cirrhosis and sepsis where levels in serum can increase 10 to 50 fold during acute inflammation [10,11]
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