Dynamic Changes in Amino Acid Concentration Profiles in Patients with Sepsis

<div><p>Objectives</p><p>The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies.</p><p>Methods</p><p>Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU) admission, and the serum concentrations of 42 amino acids were measured.</p><p>Results</p><p>The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs), especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively.</p><p>Conclusions</p><p>Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic.</p><p>Trial Registration</p><p>ClinicalTrial.gov identifier <a href="https://clinicaltrials.gov/ct2/show/NCT01818830" target="_blank">NCT01818830</a>.</p></div

The dynamic changes in cystine (A), taurine (B), and sulfur-containing amino acid (C) levels between the sepsis and severe sepsis groups on days 1, 3, 5, 7, 10, and 14.

<p>*P<0.05.</p

ROC curves for the outcome prediction value of the cystine, taurine, and sulfur-containing amino acid levels and the APACHE II and SOFA scoring systems at all time points post-admission.

<p>Sensitivity means true positive rate; 1-specificity means false positive rate; the 45-degree reference line stands for the chance diagonal, which means a diagnostic test is completely free of diagnostic value (the area under the curve equals 0.5).</p

The relationships between the APACHE II (A) and SOFA (B) scoring systems and the serum concentrations of cystine (1), taurine (2), and sulfur-containing amino acids (3) at all time points post-admission.

<p>The relationships between the APACHE II (A) and SOFA (B) scoring systems and the serum concentrations of cystine (1), taurine (2), and sulfur-containing amino acids (3) at all time points post-admission.</p

Comparison of amino acid serum concentrations among the normal control, SIRS, and sepsis groups on the day of ICU admission.

<p>AAs, amino acids; EAAs, essential AAs; NEAAs, nonessential AAs; GAAs, glycogenic AAs; BCAAs, branched-chain AAs; AAAs, aromatic AAs; SAAs, sulfur-containing AAs.</p><p>* Indicates sepsis vs. normal control groups, P<0.05;</p><p># indicates sepsis vs. SIRS groups, P<0.05;</p><p>^ indicates SIRS vs. normal control groups, P<0.05.</p><p>Comparison of amino acid serum concentrations among the normal control, SIRS, and sepsis groups on the day of ICU admission.</p

Pregnancy-Induced Metabolic Phenotype Variations in Maternal Plasma

Metabolic variations occur during normal pregnancy to provide the growing fetus with a supply of nutrients required for its development and to ensure the health of the woman during gestation. Mass spectrometry-based metabolomics was employed to study the metabolic phenotype variations in the maternal plasma that are induced by pregnancy in each of its three trimesters. Nontargeted metabolomics analysis showed that pregnancy significantly altered the profile of metabolites in maternal plasma. The levels of six metabolites were found to change significantly throughout pregnancy, with related metabolic pathway variations observed in biopterin metabolism, phospholipid metabolism, amino acid derivatives, and fatty acid oxidation. In particular, there was a pronounced elevation of dihydrobiopterin (BH₂), a compound produced in the synthesis of dopa, dopamine, norepinephrine, and epinephrine, in the second trimester, whereas it was markedly decreased in the third trimester. The turnover of BH₂ and tryptophan catabolites indicated that the fluctuations of neurotransmitters throughout pregnancy might reveal the metabolic adaption in the maternal body for the growth of the fetus. Furthermore, 11 lipid classes and 41 carnitine species were also determined and this showed variations in the presence of long-chain acylcarnitines and lysophospholipids in later pregnancy, suggesting changes of acylcarnitines and lysophospholipids to meet the energy demands in pregnant women. To our knowledge, this work is the first report of dynamic metabolic signatures and proposed related metabolic pathways in the maternal plasma for normal pregnancies and provided the basis for time-dependent metabolic trajectory against which disease-related disorders may be contrasted