Nontargeted urine metabolomic analysis of acute intermittent porphyria reveals novel interactions between bile acids and heme metabolism: New promising biomarkers for the long-term management of patients.

Acute intermittent porphyria is an inherited error of heme synthesis. The underlying pathophysiology, involving mainly hepatic heme synthesis, is poorly understood despite its occurrence, and the severity of acute porphyria attack is still difficult to control. A better understanding of the interactions between heme synthesis and global metabolism would improve the management of AIP patients.

Increasing plant protein in the diet induces changes in the plasma metabolome that may be beneficial for metabolic health. A randomized crossover study in males.

Background & Aim: Dietary shifts replacing animal protein (AP) with plant protein (PP) sources have been associated with lowering cardiometabolic risk (CMR), but underlying mechanisms are poorly characterized. This nutritional intervention aims to characterize the metabolic changes induced by diets containing different proportions of AP and PP sources in males at CMR.

Design: This study is a 4-week, crossover, randomized, controlled-feeding trial in which 19 males with CMR followed two diets providing either 36 % for the control diet (CON-D) or 64 % for the flexitarian diet (FLEX-D) of total protein intake from PP sources.

Red blood cell metabolomics identify ergothioneine as a key metabolite in DMARD-naïve rheumatoid arthritis and response to methotrexate.

Using a new red blood cell (RBC) metabolite extraction protocol, we performed a metabolomic analysis on RBCs in rheumatoid arthritis (RA) patients treated or not with methotrexate (MTX), with the two following objectives: to compare the RBC metabolic profiles of MTX-naïve RA patients and healthy controls (HC), and to investigate whether RBC profiles before and after MTX treatment in RA differed between responders and non-responders. Plasma analysis was performed in parallel. Metabolites were extracted and identified in RBCs and plasma by liquid chromatography-mass spectrometry.

Metabolomics Analysis of Rabbit Plasma after Ocular Exposure to Vapors of Sulfur Mustard.

Sulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In order to identify relevant biomarkers and to obtain a deeper understanding of the underlying biochemical events, we performed an untargeted metabolomics analysis using liquid chromatography coupled to high-resolution mass spectrometry of plasma samples from New Zealand white rabbits ocularly exposed to vapors of SM.

An orally active carbon monoxide-releasing molecule enhances beneficial gut microbial species to combat obesity in mice.

Carbon monoxide (CO), a gaseous signaling molecule, has shown promise in preventing body weight gain and metabolic dysfunction induced by high fat diet (HFD), but the mechanisms underlying these effects are largely unknown. An essential component in response to HFD is the gut microbiome, which is significantly altered during obesity and represents a target for developing new therapeutic interventions to fight metabolic diseases. Here, we show that CO delivered to the gut by oral administration with a CO-releasing molecule (CORM-401) accumulates in faeces and enriches a variety of microbial species that were perturbed by a HFD regimen.

In-depth characterization of a selection of gut commensal bacteria reveals their functional capacities to metabolize dietary carbohydrates with prebiotic potential.

Unlabelled: The microbial utilization of dietary carbohydrates is closely linked to the pivotal role of the gut microbiome in human health. Inherent to the modulation of complex microbial communities, a prebiotic implies the selective utilization of a specific substrate, relying on the metabolic capacities of targeted microbes. In this study, we investigated the metabolic capacities of 17 commensal bacteria of the human gut microbiome toward dietary carbohydrates with prebiotic potential.

Metabolomic changes in adults with status epilepticus: A human case-control study.

Objective: Status epilepticus (SE) is a life-threatening prolonged epileptic seizure that affects ~40 per 100 000 people yearly worldwide. The persistence of seizures may lead to excitotoxic processes, neuronal loss, and neuroinflammation, resulting in long-term neurocognitive and functional disabilities. A better understanding of the pathophysiological mechanisms underlying SE consequences is crucial for improving SE management and preventing secondary neuronal injury.

Uveitic glaucoma-like features in Yap conditional knockout mice.

Glaucoma is a multifactorial neurodegenerative disease characterized by the progressive and irreversible degeneration of the optic nerve and retinal ganglion cells. Despite medical advances aiming at slowing degeneration, around 40% of treated glaucomatous patients will undergo vision loss. It is thus of utmost importance to have a better understanding of the disease and to investigate more deeply its early causes.

Assessment of local and systemic signature of eosinophilic esophagitis (EoE) in children through multi-omics approaches.

Background: Eosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers.

Development of an Untargeted Metabolomics Strategy to Study the Metabolic Rewiring of Dendritic Cells upon Lipopolysaccharide Activation.

Dendritic cells (DCs) are essential immune cells for defense against external pathogens. Upon activation, DCs undergo profound metabolic alterations whose precise nature remains poorly studied at a large scale and is thus far from being fully understood. The goal of the present work was to develop a reliable and accurate untargeted metabolomics workflow to get a deeper insight into the metabolism of DCs when exposed to an infectious agent (lipopolysaccharide, LPS, was used to mimic bacterial infection).

Despite similar clinical features metabolomics reveals distinct signatures in insulin resistant and progressively obese minipigs.

Obesity is a major contributor to the silent and progressive development of type 2 diabetes (T2D) whose prevention could be improved if individuals at risk were identified earlier. Our aim is to identify early phenotypes that precede T2D in diet-induced obese minipigs. We fed four groups of minipigs (n = 5-10) either normal-fat or high-fat high-sugar diet during 2, 4, or 6 months.

Identification of the Major Degradation Pathways of Selumetinib.

Selumetinib is administered orally in capsule form and is indicated for the treatment of neurofibromatosis. To facilitate dosage adjustments, liquid preparations, such as solutions or suspensions, are to be developed. This led, first, to determine the stability profile of soluble or dispersed selumetinib and, secondly, to look for ways to stabilize the active substance.

The Human Meconium Metabolome and Its Evolution during the First Days of Life.

Meconium represents the first newborn stools, formed from the second month of gestation and excreted in the first days after birth. As an accumulative and inert matrix, it accumulates most of the molecules transferred through the placenta from the mother to the fetus during the last 6 months of pregnancy, and those resulting from the metabolic activities of the fetus. To date, only few studies dealing with meconium metabolomics have been published.

Cystine uptake inhibition potentiates front-line therapies in acute myeloid leukemia.

By querying metabolic pathways associated with leukemic stemness and survival in multiple AML datasets, we nominated SLC7A11 encoding the xCT cystine importer as a putative AML dependency. Genetic and chemical inhibition of SLC7A11 impaired the viability and clonogenic capacity of AML cell lines in a cysteine-dependent manner. Sulfasalazine, a broadly available drug with xCT inhibitory activity, had anti-leukemic activity against primary AML samples in ex vivo cultures.

Chronic Consumption of Cocoa Rich in Procyanidins Has a Marginal Impact on Gut Microbiota and on Serum and Fecal Metabolomes in Male Endurance Athletes.

Cocoa is used in the sports world as a supplement, although there is no consensus on its use. We investigated the effect of cocoa intake on intestinal ischemia (intestinal fatty acid-binding protein (I-FABP)), serum lipopolysaccharide (LPS) levels, gastrointestinal symptoms, and gut microbiota in endurance athletes during their training period on an unrestricted diet. We also performed a metabolomics analysis of serum and feces after a bout of exercise before and after supplementation.

ProMetIS, deep phenotyping of mouse models by combined proteomics and metabolomics analysis.

Genes are pleiotropic and getting a better knowledge of their function requires a comprehensive characterization of their mutants. Here, we generated multi-level data combining phenomic, proteomic and metabolomic acquisitions from plasma and liver tissues of two C57BL/6 N mouse models lacking the Lat (linker for activation of T cells) and the Mx2 (MX dynamin-like GTPase 2) genes, respectively. Our dataset consists of 9 assays (1 preclinical, 2 proteomics and 6 metabolomics) generated with a fully non-targeted and standardized approach.

Metabolomics in the understanding and management of hepatic encephalopathy.

Metabolomics refers to the study of biological components below 1000 Daltons (Da) involved in metabolic pathways as substrates, products or effectors. According to the interconnected metabolic disturbances that have been described in the pathophysiology of hepatic encephalopathy (HE), this technique appears to be well adapted to study and better delineate the disease. This review will focus on recent advances in metabolomics in the field of HE.