Figure 3. Comparisons of the plasma metabolome in community-acquired sepsis survivors and nonsurvivors.
(A) Comparison of annotated plasma metabolite concentrations at t24 in 132 discovery subjects (represented by columns). Individuals who died were ordered by days-to-death (decreasing from left to right as indicated by the black triangle). Rows show 82 host metabolites with statistically significant differences between groups (stratified ANOVA, p<0.05). Colors indicate log-transformed standardized values. Highlighted are 13 acyl-glycerophosphocholines (GPCs) and acyl-glycerophosphoethanolamines (GPEs), which were decreased in sepsis survivors and further decreased in sepsis nonsurvivors (in comparison with controls), 13 RNA catabolites and 14 acyl-carnitines, both of which were decreased in sepsis survivors and increased in sepsis nonsurvivors (in comparison with controls). Detailed images in supplementary materials (Fig. S5). (B–D) Three-dimensional scatterplots showing plasma acyl-carnitine and acyl-GPC concentrations in 378 samples, as measured by quantitative, targeted assays. (B, C) Acylcarnitine concentrations were generally increased in day-28 sepsis nonsurvivors (green contour ellipsoid) and decreased in sepsis survivors (blue ellipsoid) when compared with non-infected controls (red ellipsoid). Samples obtained from patients who died with sepsis within the 28 day follow-up period are indicated by green diamonds (n=93; 4-cis-decenoylcarnitine 1825±168 mg/dL; hexanoylcarnitine 41.2±3.5 mg/dL; butyroylcarnitine 68.2±11.7 mg/dL [mean±S.E.M.]), sepsis survivors by blue dots (n=235; 4-cis-decenoylcarnitine 932±50 mg/dL; hexanoylcarnitine 20.3±1.1 mg/dL; butyroylcarnitine 31.9±2.3 mg/dL) and non-infected controls by red dots (n=54; 4-cis-decenoylcarnitine 1200±115 mg/dL; hexanoylcarnitine 24.6±2.9 mg/dL; butyroylcarnitine 35.0±3.7 mg/dL). (D) Three -dimensional scatterplot showing similar trends in plasma values of two acyl-glycerophosphocholines (acyl-GPCs) and an RNA catabolite in 378 samples. Acyl-GPCs generally were highest in non-infected (red contour ellipsoid), lower in sepsis survivors (blue contour ellipsoid) and lowest in day-28 sepsis nonsurvivors (green contour ellipsoid). Sepsis day 28-deaths are shown by green diamonds (n=93; 1-arachidonoyl-GPC 1.10±0.09 mg/dL; 1-linoleoyl-GPC 2.23±0.21 mg/dL; pseudouridine 954±65 mg/dL [mean±S.E.M.]), sepsis survivors by blue dots (n=235; 1-arachidonoyl-GPC 1.38±0.07 mg/dL; 1-linoleoyl-GPC 3.40±0.29 mg/dL; pseudouridine 708±43 mg/dL) and non-infected controls by red dots (n=54; 1-arachidonoyl-GPC 2.49±0.13mg/dL; 1-linoleoyl-GPC 6.15±0.52 mg/dL; pseudouridine 628±88 mg/dL). Ellipsoids encompass 90% of sample values. (E). Box and whisker plots of MS lactate values and targeted, quantitative values (red boxes) in 378 plasma samples. Sample values are shown in black. Ranges are shown by black horizontal lines. Means are connected by blue lines.