DiscussionDerangement in gut barrier function occurs in many clinical settings. Endotoxin translocation has been never evidenced in some cases and more frequently than in systemic bacterial translocation. Still, endotoxin is only representative of Gram-negative bacteria, microbial translocation may occur more regularly than previously reported after endotoxin measurement. The aim of this study was: to develop a tool allowing us to measure PGN, representative of both Gram-negative and Gram-positive; to address its presence within the bloodstream of patients in a clinical situation known to favor translocation of microbial products; to perform a survey during and after surgery to assess the frequency of the translocation of microbial products; and to attempt linking PGN translocation with the inflammatory process.

AAS is thought to be associated with endotoxin and bacterial translocation through the gut barrier, following manipulation of the gut by the surgeon and aortic clamping. However, evidence to prove this link was difficult to gather, probably because bacteria translocated into the bloodstream are rapidly killed and do not give rise to positive hemocultures [30,34]. Several studies, including ours, aimed to address this question by measuring circulating endotoxin [8,9]. However, this approach is hindered by the presence of many interfering or blocking molecules (soluble CD14, LPS-binding protein, lipoproteins) [15,16,35]. Thus the determination of LPS levels in the plasma of patients after surgery was not reliable enough, and did not allow for the demonstration that translocation was taking place systematically.

In the present study, we set up a new method for detecting bacterial NOD2 agonist in plasma, using a cell line transfected with NOD2, a general sensor of PGN through its minimal motif MDP [20,21], and a reporter gene under the control of the NF-��B transcription factor. Measurement of PGN is relevant in many aspects. First, it is the major component of Gram-positive bacteria and is also found in Gram-negative bacteria. Thus, when LPS detection addresses only Gram-negative bacteria, PGN detection addresses both types. Second, we showed that our system efficiently detected anaerobic bacterial PGN, expected to be more representative of the intestinal flora. Finally, the specificity of our test was confirmed by the use of a frameshift mutant of NOD2, which cannot be activated by bacterial PGN or its fragment [20,21].

This system showed that translocation of pathogen-associated molecular patterns (PAMPs) occurred in abdominal aortic surgery with a frequency higher than that measured so far, and that the assay of NOD2 agonist in plasma is a useful and sensitive tool for early detection of a bacterial product in the bloodstream. As the exact Dacomitinib nature of circulating PGN is unknown, we used the terms ‘NOD2 agonist’ to name the circulating PAMP found in patients’ plasma.