Novel Biomarker Candidates for Febrile Neutropenia in Hematological Patients Using Nontargeted Metabolomics

Background. Novel potential small molecular biomarkers for sepsis were analyzed with nontargeted metabolite profiling to find biomarkers for febrile neutropenia after intensive chemotherapy for hematological malignancies. Methods. Altogether, 85 patients were included into this prospective study at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The plasma samples for the nontargeted metabolite profiling analysis by liquid chromatography-mass spectrometry were taken when fever rose over 38° and on the next morning. Results. Altogether, 90 differential molecular features were shown to explain the differences between patients with complicated (bacteremia, severe sepsis, or fatal outcome) and noncomplicated courses of febrile neutropenia. The most differential compounds were an androgen hormone, citrulline, and phosphatidylethanolamine PE(18:0/20:4). The clinical relevance of the findings was evaluated by comparing them with conventional biomarkers like C-reactive protein and procalcitonin. Conclusion. These results hold promise to find out novel biomarkers for febrile neutropenia, including citrulline. Furthermore, androgen metabolism merits further studies.</p

Decreased plasma serotonin and other metabolite changes in healthy adults after consumption of wholegrain rye: an untargeted metabolomics study

International audienceBackground: Wholegrain consumption has been associated with beneficial health effects including reduction of diabetes and cancer risk; however, the underlying mechanisms are not fully understood. Objective: The aim of this study was to characterize the effects of wholegrain rye intake on circulating metabolites in a human intervention study using untargeted metabolomics. Methods: The intervention consisted of 2 successive 4-wk periods in a randomized crossover design, where 15 adults consumed wholegrain rye bread (WGR) or white wheat bread enriched with fermented rye bran (WW+RB), following a 4-wk rye-free period with white wheat bread (WW). Fasting plasma samples were collected at the end of each period and analyzed using liquid chromatography-mass spectrometry. Metabolic profiles were compared to identify compounds discriminating WGR from the WW+RB and WW periods. Because peripheral serotonin is produced mainly in the gut, a hypothesis of its altered biosynthesis as a response to increased cereal fiber intake was tested by measuring intestinal serotonin of mice fed for 9 wk on a high-fat diet supplemented with different sources of fiber (rye bran flour, ground wheat aleurone, or powdered cellulose). Results: Five endogenous metabolites and 15 rye phytochemicals associated with WGR intake were identified. Plasma concentrations of serotonin, taurine, and glycerophosphocholine were significantly lower after the WGR than WW period (Q < 0.05). Concentrations of 2 phosphatidylethanolamine plasmalogens, PE(18:2/P-18:0) and PE(18:2/P-16:0), were lower after the WGR period than the WW+RB period (Q < 0.05). The concentration of serotonin was significantly lower in the colonic tissue of mice that consumed rye bran or wheat aleurone compared with cellulose (P < 0.001). Conclusions: Wholegrain rye intake decreases plasma serotonin in healthy adults when compared with refined wheat. Intake of rye bran and wheat aleurone decreases colonic serotonin in mice. These results suggest that peripheral serotonin could be a potential link between wholegrain consumption and its associated health effects. Data used in the study were derived from a trial registered at www.clinicaltrials.gov as NCT03550365

A non-targeted LC–MS metabolic profiling of pregnancy:longitudinal evidence from healthy and pre-eclamptic pregnancies

Abstract Introduction: Maternal metabolism changes substantially during pregnancy. However, few studies have used metabolomics technologies to characterize changes across gestation. Objectives and methods: We applied liquid chromatography–mass spectrometry (LC–MS) based non-targeted metabolomics to determine whether the metabolic profile of serum differs throughout the pregnancy between pre-eclamptic and healthy women in the FINNPEC (Finnish Genetics of Preeclampsia Consortium) Study. Serum samples were available from early and late pregnancy. Results: Progression of pregnancy had large-scale effects to the serum metabolite profile. Altogether 50 identified metabolites increased and 49 metabolites decreased when samples of early pregnancy were compared to samples of late pregnancy. The metabolic signatures of pregnancy were largely shared in pre-eclamptic and healthy women, only urea, monoacylglyceride 18:1 and glycerophosphocholine were identified to be increased in the pre-eclamptic women when compared to healthy controls. Conclusions: Our study highlights the need of large-scale longitudinal metabolomic studies in non-complicated pregnancies before more detailed understanding of metabolism in adverse outcomes could be provided. Our findings are one of the first steps for a broader metabolic understanding of the physiological changes caused by pregnancy per se.Collaborators for The FINNPEC Core Investigator Group Eero Kajantie (Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland). Juha Kere (Department of Biosciences and Nutrition, and Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden; Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland), Katja Kivinen (Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland), Anneli Pouta (Department of Government Services, National Institute for Health and Welfare, Helsinki, Finland)