Septic shock is the most severe phase of sepsis and is associated with high rates of mortality. However, early stage prediction of septic shock outcomes remains difficult. Metabolomic techniques have emerged as a promising tool for improving prognosis. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models separating the serum metabolomes of survivors from those of non-survivors were established with samples obtained at the intensive care unit (ICU) admission (H0) and 24 h later (H24). For 51 patients with available H0 and H24 samples, multi-level modeling was performed to provide insight into different metabolic evolutions that occurred between H0 and H24 in the surviving and non-surviving patients. Relative quantification and receiver operational characteristic curves (ROC) were applied to estimate the predictability of key discriminatory metabolites for septic shock mortality. Metabolites that were involved in energy supply and protein breakdown were primarily responsible for differentiating survivors from non-survivors. This was not only seen in the H0 and H24 discriminatory models, but also in the H0-H24 paired models. Reanalysis of extra H0-H24 paired samples in the established multi-level model demonstrated good performance of the model for the classification of samplings. According to the ROC results, nine discriminatory metabolites defined consistently from the unpaired model and the H0-H24 time-trend change (ΔH24-H0) show good prediction of mortality. These results suggest that NMR-based metabolomic analysis is useful for a better overall assessment of septic shock patients. Dysregulation of the metabolites identified by this study is associated with poor outcomes for septic shock. Evaluation of these compounds during the first 24 h after ICU admission in the septic shock patient may be helpful for estimating the severity of cases and for predicting outcomes. All human serum samples were collected and stored, provided by the “center of biologic resources for liver disease”, in Jean Verdier Hospital, Bondy, France (BB-0033-00027).

Background: The prevention and early screening of PCa is highly dependent on the identification of new biomarkers. In this study, we investigated whether plasma metabolic profiles from healthy males provide novel early biomarkers associated with future risk of PCa. Methods: Using the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, we identified plasma samples collected from 146 PCa cases up to 13 years prior to diagnosis and 272 matched controls. Plasma metabolic profiles were characterized using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Results: Orthogonal partial least squares discriminant analysis (OPLS-DA) discriminated PCa cases from controls, with a median area under the receiver operating characteristic curve (AU-ROC) of 0.92 using a 1000-time repeated random sub-sampling validation. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) identified the top 10 most important metabolites (p < 0.001) discriminating PCa cases from controls. Among them, phosphate, ethyl oleate, eicosadienoic acid were higher in individuals that developed PCa than in the controls during the follow-up. In contrast, 2-hydroxyadenine, sphinganine, L-glutamic acid, serotonin, 7-keto cholesterol, tiglyl carnitine, and sphingosine were lower. Conclusion: Our results support the dysregulation of amino acids and sphingolipid metabolism during the development of PCa. After validation in an independent cohort, these signatures may promote the development of new prevention and screening strategies to identify males at future risk of PCa.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that usually affects young adults. The development of MS is closely related to the changes in the metabolome. Metabolomics studies have been performed using biofluids or tissue samples from rodent models and human patients to reveal metabolic alterations associated with MS progression. This review aims to provide an overview of the applications of metabolomics that for the investigations of the perturbed metabolic pathways in MS and to reveal the potential of metabolomics in personalizing treatments. In conclusion, informative variations of metabolites can be potential biomarkers in advancing our understanding of MS pathogenesis for MS diagnosis, predicting the progression of the disease, and estimating drug effects. Metabolomics will be a promising technique for improving clinical care in MS.

Sepsis, a life-threatening organ dysfunction caused by dysregulated host responses to infection, often leads to sepsis-associated acute lung injury (SALI), a major contributor to mortality. Spermidine (SPD), a natural polyamine with anti-inflammatory and metabolic regulatory properties, has emerged as a potential nutritional adjunct for sepsis management. However, whether and how SPD ameliorates SALI remains to be elucidated. Here, cecal ligation and puncture (CLP) was performed in rats to simulate sepsis. Rat survival, lung injury score, Dry/Wet ratio, histopathology, cytokine levels and immunohistochemical analysis were analyzed to evaluate SPD’s effects on SALI. Targeted metabolomics, molecular docking and cellular thermal shift assay (CETSA) identified AMP-activated protein kinase (AMPK) as an underlying target of SPD’s action. In vitro investigations were based on lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs), with flow cytometry assessing apoptosis. AMPK inhibitor (Compound C) and downstream signaling were examined in vivo and in vitro through q-PCR and Western blot experiments. Consequently, SPD improved rat survival, reduced lung injury, and decreased pro-inflammatory cytokines in CLP rats. Metabolomics, molecular docking and CETSA suggested AMPK-mediated energy metabolism modulation. Mechanistically, SPD attenuated necroptosis via AMPK/RIPK1/MLKL signaling. Moreover, Compound C counteracted the protective effect of SPD on SALI in vivo and in vitro. Our findings evidence that SPD significantly ameliorates SALI via the regulation of AMPK-mediated necroptosis. SPD supplementation may serve as a complementary therapeutic approach, warranting further investigation in subsequent clinical trials for sepsis treatment.