Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children.

Aims/hypothesis: Appearance of multiple islet cell autoantibodies in early life is indicative of future progression to overt type 1 diabetes, however, at varying rates. Here, we aimed to study whether distinct metabolic patterns could be identified in rapid progressors (RP, disease manifestation within 18 months after the initial seroconversion to autoantibody positivity) vs. slow progressors (SP, disease manifestation at 60 months or later from the appearance of the first autoantibody). Methods: Longitudinal samples were collected from RP (n=25) and SP (n=41) groups at the ages of 3, 6, 12, 18, 24, or ≥ 36 months. We performed a comprehensive metabolomics study, analyzing both polar metabolites and lipids. The sample series included a total of 239 samples for lipidomics and 213 for polar metabolites. Results: We observed that metabolites mediated by gut microbiome, such as those involved in tryptophan metabolism, were the main discriminators between RP and SP. The study identified specific circulating molecules and pathways, including amino acid (threonine), sugar derivatives (hexose), and quinic acid that may define rapid vs. slow progression to type 1 diabetes. However, the circulating lipidome did not appear to play a major role in differentiating between RP and SP. Conclusion/interpretation: Our study suggests that a distinct metabolic profile is linked with the type 1 diabetes progression. The identification of specific metabolites and pathways that differentiate RP from SP may have implications for early intervention strategies to delay the development of type 1 diabetes.

Dynamics of the Lipidome in a Colon Simulator.

Current evidence suggests that gut microbiome-derived lipids play a crucial role in the regulation of host lipid metabolism. However, not much is known about the dynamics of gut microbial lipids within the distinct gut biogeographic. Here we applied targeted and untargeted lipidomics to in vitro-derived feces. Simulated intestinal chyme was collected from in vitro gut vessels (V1-V4), representing proximal to distal parts of the colon after 24 and 48 h with/without polydextrose treatment. In total, 44 simulated chyme samples were collected from the in vitro colon simulator. Factor analysis showed that vessel and time had the strongest impact on the simulated intestinal chyme lipid profiles. We found that levels of phosphatidylcholines, sphingomyelins, triacylglycerols, and endocannabinoids were altered in at least one vessel (V1-V4) during simulation. We also found that concentrations of triacylglycerols, diacylglycerols, and endocannabinoids changed with time (24 vs. 48 h of simulation). Together, we found that the simulated intestinal chyme revealed a wide range of lipids that remained altered in different compartments of the human colon model over time.

Serum metabolome associated with severity of acute traumatic brain injury.

Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Ozonation of carbamazepine and its main transformation products: product determination and reaction mechanisms.

Carbamazepine (CBZ) is a recalcitrant pharmaceutical often detected in wastewater and in the environment. CBZ can be removed from wastewater through advanced oxidation treatment methods such as ozonation. In this study, CBZ and its transformation product 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD) were ozonated, and the formation and transformation of their ozonation products were investigated using liquid chromatography coupled to ion trap mass spectrometry and high-resolution mass spectrometry as well as nuclear magnetic resonance (NMR). The main products, 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM) and BQD were quantified using isolated standards and LC-UV. Of the original CBZ concentration, 74% was transformed into BQM and 83% of BQM was further transformed into BQD. Both products are more stable than CBZ and could still be detected after 240 min of ozonation. Another major product, 2,2'-azanediyldibenzaldehyde (TP225) was for the first time identified using NMR. Twelve further CBZ products were identified.

Catalytic ozonation of the antibiotic sulfadiazine: Reaction kinetics and transformation mechanisms.

In this work, ozone has been used to study the transformation of the antibiotic sulfadiazine (SDZ). SDZ and its transformation products was investigated using liquid chromatography coupled to mass spectrometry and using NMR. The results revealed that 6% of SDZ is transformed into 2-aminopyrimidine. A significant amount of SDZ undergoes a rearrangement reaction followed by ring-closing reactions. One of these products, SDZ-P15, is the main product after 240 min of ozonation. Almost 30% of SDZ transforms into SDZ-P15. SDZ was also transformed via the addition of one or more hydroxyl groups, via the oxidation of an amine group to a nitro group as well as via a bond cleavage reaction. Most of the intermediate products presented in this study have not previously been reported as SDZ transformation products formed using ozonation technology.

Bacterial diversity and population shifts driven by spotlight wastewater micropollutants in low-temperature highly nitrifying activated sludge.

In this study the influence of low-temperature (8°C), sludge retention time (SRT) and loading of spotlight wastewater micropollutants (MPs) on bacterial community of activated sludge was investigated with a special focus on nitrification. Two Sequencing batch reactors (SBR) and two membrane bioreactors (MBR) were operated with synthetic municipal-like wastewater receiving and not receiving ibuprofen, diclofenac, estrone and 17α-ethynylestradiol (EE2). Bacterial population studies were related to removal efficiencies of studied MPs. The results showed that studied bacterial communities significantly differed from all previously published nitrifying activated sludge communities. Exceptionally low concentration of autotrophic nitrifying bacteria were found (<0.5%) as well as no common heterotrophic nitrifies were presenting in activated sludge and therefore could not be related to the MPs removal. Additionally SRT had a spacious effect on the diversity of bacteria and bacterial population shifts under pressure of MPs. Growth of Firmicutes was suppressed by presence of MPs in all the reactors. Increase of MPs concentrations in wastewater improved the removal of EE2. Abundance of Delta- and Gammaproteobacteria showed positive correlation with diclofenac removal.

Comparative study of emerging micropollutants removal by aerobic activated sludge of large laboratory-scale membrane bioreactors and sequencing batch reactors under low-temperature conditions.

Four emerging micropollutants ibuprofen, diclofenac, estrone (E1) and 17α-ethinylestradiol (EE2) were studied in large laboratory-scale wastewater treatment plants (WWTPs) with high nitrifying activity. Activated sludge (AS) with sludge retention times (SRTs) of 12days and 14days in sequencing batch reactors (SBRs) and 30days, 60days and 90days in membrane bioreactors (MBRs) were examined at 8°C and 12°C. Concentrations of pharmaceuticals and their main metabolites were analysed in liquid phase and solid phase of AS by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A remarkable amount of contaminants were detected in solids of AS, meaning the accumulation of micropollutants in bacterial cells. The biodegradation rate constants (Kbiol) were affected by SRT and temperature. MBR with a 90-day SRT showed the best results of removal. Conventional SBR process was inefficient at 8°C showing Kbiol values lower than 0.5lgSS(-1)d(-1) for studied micropollutants.