Involvement of Aromatic Metabolites in the Pathogenesis of Septic Shock

We hypothesized that aromatic microbial metabolites (AMM), such as phenyllactic (PhLA), p-hydroxyphenylacetic (p-HPhAA), and p-hydroxyphenyllactic (p-HPhLA) acids, contribute to the pathogenesis of septic shock.Clinical and laboratory data of patients with community-acquired pneumonia were obtained on intensive care unit admission and the next day. Patients were divided into two groups based on septic shock presence or absence. The levels of AMM (PhLA, p-HPhAA, p-HPhLA, and their sum, ∑3AMM), catecholamine metabolites (3,4-dihydroxymandelic [DHMA], 3,4-dihydroxyphenylacetic [DOPAC], and homovanillic [HVA] acids), lactate, N-terminal pro-brain natriuretic peptide (NT-proBNP), inducible nitric oxide synthase (iNOS), and procalcitonin (PCT) were compared. Correlations between AMM and clinical and laboratory data were calculated.There were 20 patients in the septic shock group and 21 in the nonseptic shock group. On admission, the septic shock patients demonstrated significantly higher levels of PhLA (2.3 vs. 0.8 μmol/L), p-HPhAA (4.6 vs. 1.4 μmol/L), p-HPhLA (7.4 vs. 2.6 μmol/L), HVA, lactate, and significantly lower levels of iNOS. The next day, the two groups also showed significant differences in the levels of PCT and NT-proBNP. The correlation between ∑3AMM and presence of shock, levels of lactate, HVA, and NT-proBNP on admission was 0.44, 0.67, 0.57, and 0.38, respectively, and the correlation on the next day was 0.59, 0.73, 0.76, and 0.6, respectively (P < 0.01). These findings can be explained by the ability of AMM to reduce tyrosine hydroxylase activity, thus limiting the synthesis of catecholamines.AMM are involved in the pathogenesis of septic shock.