Gas Chromatography-Mass Spectrometry (GC-MS) Metabolites Analysis in Endometriosis Patients: A Prospective Observational Translational Study.

BACKGROUND: Endometriosis affects women of reproductive age, and its pathogenesis is still unclear. Typically, it overlaps other similar medical and surgical conditions, determining a delay in early diagnosis. Metabolomics allows studying metabolic changes in different physiological or pathological states to discover new potential biomarkers. We used the gas chromatography-mass spectrometer (GC-MS) to explore metabolic alterations in endometriosis to better understand its pathophysiology and find new biomarkers. METHODS: Twenty-two serum samples of patients with symptomatic endometriosis and ten without it were collected and subjected to GC-MS analysis. Multivariate and univariate statistical analyses were performed, followed by pathway analysis. RESULTS: Partial least squares discriminant analysis was performed to determine the differences between the two groups (p = 0.003). Threonic acid, 3-hydroxybutyric acid, and proline increased significantly in endometriosis patients, while alanine and valine decreased. ROC curves were built to test the diagnostic power of metabolites. The pathway analysis identified the synthesis and degradation of ketone bodies and the biosynthesis of phenylalanine, tyrosine, and tryptophan as the most altered pathways. CONCLUSIONS: The metabolomic approach identifies metabolic alterations in women with endometriosis. These findings may improve our understanding of the pathophysiological mechanisms of disease and the discovery of new biomarkers.

Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines.

High-dose of vitamin C (L-ascorbic acid, ascorbate) exhibits anti-tumoral effects, primarily mediated by pro-oxidant mechanisms. This cytotoxic effect is thought to affect the reciprocal crosstalk between redox balance and cell metabolism in different cancer types. Vitamin C also inhibits the growth of papillary thyroid carcinoma (PTC) cells, although the metabolic and redox effects remain to be fully understood. To shed light on these aspects, PTC-derived cell lines harboring the most common genetic alterations characterizing this tumor were used. Cell viability, apoptosis, and the metabolome were explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, and UHPLC/MS. Changes were observed in redox homeostasis, with increased reactive oxygen species (ROS) level and perturbation in antioxidants and electron carriers, leading to cell death by both apoptosis and necrosis. The oxidative stress contributed to the metabolic alterations in both glycolysis and TCA cycle. Our results confirm the pro-oxidant effect of vitamin C as relevant in triggering the cytotoxicity in PTC cells and suggest that inhibition of glycolysis and alteration of TCA cycle via NAD+ depletion can play an important role in this mechanism of PTC cancer cell death.

Clinical Phenotypes of Parkinson's Disease Associate with Distinct Gut Microbiota and Metabolome Enterotypes.

Parkinson's disease (PD) is a clinically heterogenic disorder characterized by distinct clinical entities. Most studies on motor deficits dichotomize PD into tremor dominant (TD) or non-tremor dominant (non-TD) with akinetic-rigid features (AR). Different pathophysiological mechanisms may affect the onset of motor manifestations. Recent studies have suggested that gut microbes may be involved in PD pathogenesis. The aim of this study was to investigate the gut microbiota and metabolome composition in PD patients in relation to TD and non-TD phenotypes. In order to address this issue, gut microbiota and the metabolome structure of PD patients were determined from faecal samples using 16S next generation sequencing and gas chromatography-mass spectrometry approaches. The results showed a reduction in the relative abundance of Lachnospiraceae, Blautia, Coprococcus, Lachnospira, and an increase in Enterobacteriaceae, Escherichia and Serratia linked to non-TD subtypes. Moreover, the levels of important molecules (i.e., nicotinic acid, cadaverine, glucuronic acid) were altered in relation to the severity of phenotype. We hypothesize that the microbiota/metabolome enterotypes associated to non-TD subtypes may favor the development of gut inflammatory environment and gastrointestinal dysfunctions and therefore a more severe α-synucleinopathy. This study adds important information to PD pathogenesis and emphasizes the potential pathophysiological link between gut microbiota/metabolites and PD motor subtypes.

Metabolic Alteration in Plasma and Biopsies From Patients With IBD.

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, with periods of latency alternating with phases of exacerbation, and include 2 forms: Crohn disease (CD) and ulcerative colitis (UC). Although the etiology of IBD is still unclear, the identification and understanding of pathophysiological mechanisms underlying IBD could reveal newly targeted intestinal alterations and determine therapeutic approaches. METHODS: In this study, by using gas chromatography-mass spectrometry, we characterized plasma and biopsies from the metabolomics profiles of patients with IBD compared with those of a control group. RESULTS: The results showed a different metabolomics profile between patients with CD (n = 50) and patients with UC (n = 82) compared with the control group (n = 51). Multivariate statistical analysis of the identified metabolites in CD and UC showed changes in energetic metabolism, and lactic acid and ornithine in particular were altered in both plasma and colon biopsies. Moreover, metabolic changes were evidenced between the normal ileum and colon tissues. These differences disappeared when we compared the inflamed ileum and colon tissues, suggesting a common metabolism. CONCLUSIONS: This study showed how the metabolomics profile could be a potential tool to identify intestinal alterations associated with IBD and may have application in precision medicine and for better defining the pathogenesis of the disease.

Metabolic Profile of Patients with Severe Endometriosis: a Prospective Experimental Study.

Endometriosis is a common disease affecting women in reproductive age. There are several hypotheses on the pathogenesis of this disease. Often, its lesions and symptoms overlap with those of many other medical and surgical conditions, causing a delay in diagnosis. Metabolomics represents a useful diagnostic tool for the study of metabolic changes during a different physiological or pathological status. We used 1H-NMR to explore metabolic alteration in a cohort of patients with endometriosis in order to contribute to a better understanding of the pathophysiology of the disease and to suggest new useful biomarkers. Thirty-seven patients were recruited for the metabolomic analysis: 22 patients affected by symptomatic endometriosis and 15 not affected by it. Their serum samples were collected and analyzed with 1H-NMR. Multivariate statistical analysis was conducted, followed by univariate and pathway analyses. Partial Least Square Discriminant Analysis (PLS-DA) was performed to determine the presence of any differences between the non-endometriosis and endometriosis samples (R2X = 0.596, R2Y = 0.713, Q2 = 0.635, and p < 0.0001). ß-hydroxybutyric acid and glutamine were significantly increased, whereas tryptophan was significantly decreased in the endometriosis patients. ROC curves were built to test the diagnostic power of the metabolites (ß-hydroxybutyric acid: AUC = 0.85 CI = 0.71-0.99; glutamine: AUC = 0.83 CI = 0.68-0.98; tryptophan: AUC = 0.75 CI = 0.54-0.95; ß-hydroxybutyric acid + glutamine + tryptophan AUC = 0.92 CI = 0.81-1). The metabolomic approach enabled the identification of several metabolic alterations occurring in women with endometriosis. These findings may provide new bases for a better understanding of the pathophysiological mechanisms of the disease and for the discovery of new biomarkers. Trial registration number NCT02337816.

Gut microbiota and metabolome distinctive features in Parkinson disease: Focus on levodopa and levodopa-carbidopa intrajejunal gel.

BACKGROUND AND PURPOSE: Recent data suggest that imbalances in the composition of the gut microbiota (GM) could exacerbate the progression of Parkinson disease (PD). The effects of levodopa (LD) have been poorly assessed, and those of LD-carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and LCIG, in particular, on the GM and metabolome. METHODS: Fecal DNA samples from 107 patients with a clinical diagnosis of PD were analyzed by next-generation sequencing of the V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG group, n = 38) and on LD (LD group, n = 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve group). Fecal metabolic extracts were evaluated by gas chromatography mass spectrometry. RESULTS: The multivariate analysis showed a significantly higher abundance in the LCIG group of Enterobacteriaceae, Escherichia, and Serratia compared to the LD group. Compared to the Naïve group, the univariate analysis showed a reduction of Blautia and Lachnospirae in the LD group. Moreover, an increase of Proteobacteria, Enterobacteriaceae, and a reduction of Firmicutes, Lachnospiraceae, and Blautia was found in the LCIG group. No significant difference was found in the multivariate analysis of these comparisons. The LD group and LCIG group were associated with a metabolic profile linked to gut inflammation. CONCLUSIONS: Our results suggest that LD, and mostly LCIG, might significantly influence the microbiota composition and host/bacteria metabolism, acting as stressors in precipitating a specific inflammatory intestinal microenvironment, potentially related to the PD state and progression.

Gut Microbiota and Metabolome Alterations Associated with Parkinson's Disease.

Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson's disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson's disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson's disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson's disease.IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson's disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson's disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson's disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.

Metabolomics Fingerprint Induced by the Intranigral Inoculation of Exogenous Human Alpha-Synuclein Oligomers in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is considered a synucleinopathy because of the intraneuronal accumulation of aggregated α-synuclein (αSyn). Recent evidence points to soluble αSyn-oligomers (αSynO) as the main cytotoxic species responsible for cell death. Given the pivotal role of αSyn in PD, αSyn-based models are crucial for the investigation of toxic mechanisms and the identification of new therapeutic targets in PD. By using a metabolomics approach, we evaluated the metabolic profile of brain and serum samples of rats infused unilaterally with preformed human αSynOs (HαSynOs), or vehicle, into the substantia nigra pars compacta (SNpc). Three months postinfusion, the striatum was dissected for striatal dopamine (DA) measurements via High Pressure Liquid Chromatography (HPLC) analysis and mesencephalon and serum samples were collected for the evaluation of metabolite content via gas chromatography mass spectrometry analysis. Multivariate, univariate and correlation statistics were applied. A 40% decrease of DA content was measured in the HαSynO-infused striatum as compared to the contralateral and the vehicle-infused striata. Decreased levels of dehydroascorbic acid, myo-inositol, and glycine, and increased levels of threonine, were found in the mesencephalon, while increased contents of fructose and mannose, and a decrease in glycine and urea, were found in the serum of HαSynO-infused rats. The significant correlation between DA and metabolite content indicated that metabolic variations reflected the nigrostriatal degeneration. Collectively, the metabolomic fingerprint of HαSynO-infused rats points to an increase of oxidative stress markers, in line with PD neuropathology, and provides hints for potential biomarkers of PD.

Modulatory Effect of Nicotinic Acid on the Metabolism of Caco-2 Cells Exposed to IL-1ß and LPS.

Inflammatory bowel diseases (IBD) are the most common gastrointestinal inflammatory pathologies. Previous work evidenced a lower content of nicotinic acid (NA) in feces of IBD patients compared to healthy subjects. In the present study, we aimed to understand the effects of NA on intestinal inflammation, as several studies reported its possible beneficial effect, and investigate its influence on inflammation-driven metabolism. NA was tested on a Caco-2 in-vitro model in which inflammation was induced with interleukin-1ß (IL-1ß) and lipopolysaccharide (LPS), two mayor proinflammatory compounds produced in IBD, that stimulate the production of cytokines, such as interleukin 8. A metabolomics approach, with gas chromatography-mass spectrometry (GC-MS) and nuclear proton magnetic resonance (1H-NMR), was applied to study the metabolic changes. The results showed that NA significantly reduced the level of IL-8 produced in both LPS and IL-1ß stimulated cells, confirming the anti-inflammatory effect of NA also on intestinal inflammation. Moreover, it was demonstrated that NA treatment had a restoring effect on several metabolites whose levels were modified by treatments with IL-1ß or LPS. This study points out a possible use of NA as anti-inflammatory compound and might be considered as a promising starting point in understanding the beneficial effect of NA in IBD.

Seminal Fluid Metabolomic Markers of Oligozoospermic Infertility in Humans.

Infertility affects 12-15% of couples worldwide, and male factors are the cause of nearly half of all cases. Studying seminal fluid composition could lead to additional diagnostic accuracy and a better understanding of the pathophysiology of male factor infertility. Metabolomics offers a new opportunity to evaluate biomarkers and better understand pathological mechanisms. The aim of the study was to identify new markers or therapeutic targets to improve outcomes in male factor or idiopathic infertility patients. Semen samples were obtained from 29 men with a normal spermogram test, and from 18 oligozoospermic men. Samples were processed and analyzed by Nuclear Magnetic Resonance spectroscopy and, subsequently, multivariate and univariate statistical analyses. Receiving Operator Curves (ROC) and Spearman correlations were also performed. An Orthogonal Partial Least Square Discriminant Analysis supervised multivariate model was devised to compare the groups. The levels of fructose, myo-inositol, aspartate and choline were altered. Moreover, Spearman Correlation associated fructose, aspartate and myo-inositol with the total amount of spermatozoa, total motile spermatozoa, % of immotility and % of "in situ" spermatozoic motility respectively. NMR-based metabolomics allowed the identification of a specific metabolic fingerprint of the seminal fluids of patients affected by oligozoospermia.

Metabolic fingerprinting of chorionic villous samples in normal pregnancy and chromosomal disorders.

OBJECTIVE: Placenta-related biological samples are used in biomedical research to investigate placental development. Metabolomics represents a promising approach for studying placental metabolism in an effort to explain physiological and pathological mechanisms. The aim of this study was to investigate metabolic changes in chorionic villi during the first trimester of pregnancy in euploid and aneuploid cases. METHODS: Samples from 21 women (13 euploid and eight aneuploid) were analyzed with 1 H-nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC). Multivariate statistical analysis was performed, and differences in metabolites were used to identify the altered metabolic pathways. RESULTS: A regression model to test the correlation between fetal crown-rump length (CRL) and metabolic profile of chorionic villi was performed in euploid pregnancies (R2 was 0.69 for the NMR analysis and 0.94 for the GC-MS analysis). Supervised analysis was used to compare chorionic villi of euploid and aneuploid fetuses (NMR: R2 X = 0.70, R2 Y = 0.65, Q2  = 0.30, R2 X = 0.62; GC-MS: R2 Y = 0.704, Q2  = 0.444). Polyol pathways, myo-inositol, and oxidative stress seem to have a fundamental role in euploid and aneuploid pregnancies. CONCLUSION: Polyol pathways may have a crucial role in energy production in early pregnancy. Excessive activation in aneuploid pregnancies may lead to increased oxidative stress. Metabolomics represents a promising approach to investigate placental metabolic changes.

Metabolic characterization of amniotic fluids of fetuses with enlarged nuchal translucency.

Background In prenatal diagnosis, a thickened nuchal translucency (NT) is one of the most sensitive and specific markers for several defects but it may also be found in 5% of healthy fetuses. The pathophysiological causes that lead to an increase in NT are not yet fully understood. Metabolomics represents a new promising approach, useful for studying different metabolites in biological organisms in response to environmental stressors. The aim of our study was to investigate the metabolomic profile of the amniotic fluid samples (AFS) of euploid fetuses with enlarged nuchal translucency (ENT) compared to a control group (C group). Methods This study was carried out on a group of women who underwent second-trimester amniocentesis for advanced maternal age (C group) or for NT ≥95th percentile (ENT group) found during first-trimester aneuploidy screening. AFS were analyzed with proton nuclear magnetic resonance (1H-NMR) and high-performance liquid chromatography (HPLC), and subsequent multivariate and univariate statistical analyses were conducted, followed by pathway analysis. Results In total, 67 AFS from the C group and 23 from the ENT group were analyzed. Partial least square discriminate analysis was carried out (R2X=0.784, R2Y=0.658, Q2=0.622, P<0.0001). A different metabolic profile was observed in the ENT group compared with the C group, suggesting an energetic shift to a glycolytic phenotype in an oxidative environment in the ENT group compared to the C group. Conclusion Metabolomic studies enable the identification of metabolic alterations occurring in fetuses with ENT. These findings may provide a new basis for better understanding the pathophysiological mechanisms in this prenatal phenomenon.

Crosstalk between Metabolic Alterations and Altered Redox Balance in PTC-Derived Cell Lines.

Background: Thyroid cancer is the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most common (85⁻90%) among all the different types of thyroid carcinomas. Cancer cells show metabolic alterations and, due to their rapid proliferation, an accumulation of reactive oxygen species, playing a fundamental role in cancer development and progression. Currently, the crosstalk among thyrocytes metabolism, redox balance and oncogenic mutations remain poorly characterized. The aim of this study was to investigate the interplay among metabolic alterations, redox homeostasis and oncogenic mutations in PTC-derived cells. Methods: Metabolic and redox profile, glutamate-cysteine ligase, glutaminase-1 and metabolic transporters were evaluated in PTC-derived cell lines with distinguished genetic background (TPC-1, K1 and B-CPAP), as well as in an immortalized thyroid cell line (Nthy-ori3-1) selected as control. Results: PTC-derived cells, particularly B-CPAP cells, harboring BRAF, TP53 and human telomerase reverse transcriptase (hTERT) mutation, displayed an increase of metabolites and transporters involved in energetic pathways. Furthermore, all PTC-derived cells showed altered redox homeostasis, as reported by the decreased antioxidant ratios, as well as the increased levels of intracellular oxidant species. Conclusion: Our findings confirmed the pivotal role of the metabolism and redox state regulation in the PTC biology. Particularly, the most perturbed metabolic phenotypes were found in B-CPAP cells, which are characterized by the most aggressive genetic background.

Metabolomic Alterations in Thyrospheres and Adherent Parental Cells in Papillary Thyroid Carcinoma Cell Lines: A Pilot Study.

Papillary thyroid carcinoma (PTC), is characterized by a heterogeneous group of cells, including cancer stem cells (CSCs), crucially involved in tumor initiation, progression and recurrence. CSCs appear to have a distinct metabolic phenotype, compared to non-stem cancer cells. How they adapt their metabolism to the cancer process is still unclear, and no data are yet available for PTC. We recently isolated thyrospheres, containing cancer stem-like cells, from B-CPAP and TPC-1 cell lines derived from PTC of the BRAF-like expression profile class, and stem-like cells from Nthy-ori3-1 normal thyreocyte-derived cell line. In the present study, gas chromatography/mass spectrometry metabolomic profiles of cancer thyrospheres were compared to cancer parental adherent cells and to non cancer thyrospheres profiles. A statistically significant decrease of glycolytic pathway metabolites and variations in Krebs cycle metabolites was found in thyrospheres versus parental cells. Moreover, cancer stem-like cells showed statistically significant differences in Krebs cycle intermediates, amino acids, cholesterol, and fatty acids content, compared to non-cancer stem-like cells. For the first time, data are reported on the metabolic profile of PTC cancer stem-like cells and confirm that changes in metabolic pathways can be explored as new biomarkers and targets for therapy in this tumor.

KniMet: a pipeline for the processing of chromatography-mass spectrometry metabolomics data.

INTRODUCTION: Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow. OBJECTIVES: Merge in the same platform the steps required for metabolomics data processing. METHODS: KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform. RESULTS: The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation. CONCLUSION: KniMet provides the user with a local, modular and customizable workflow for the processing of both GC-MS and LC-MS open profiling data.

Author Correction: Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients.

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Italian cohort of patients affected by inflammatory bowel disease is characterised by variation in glycerophospholipid, free fatty acids and amino acid levels.

BACKGROUND: Inflammatory bowel disease is a group of pathologies characterised by chronic inflammation of the intestine and an unclear aetiology. Its main manifestations are Crohn's disease and ulcerative colitis. Currently, biopsies are the most used diagnostic tests for these diseases and metabolomics could represent a less invasive approach to identify biomarkers of disease presence and progression. OBJECTIVES: The lipid and the polar metabolite profile of plasma samples of patients affected by inflammatory bowel disease have been compared with healthy individuals with the aim to find their metabolomic differences. Also, a selected sub-set of samples was analysed following solid phase extraction to further characterise differences between pathological samples. METHODS: A total of 200 plasma samples were analysed using drift tube ion mobility coupled with time of flight mass spectrometry and liquid chromatography for the lipid metabolite profile analysis, while liquid chromatography coupled with triple quadrupole mass spectrometry was used for the polar metabolite profile analysis. RESULTS: Variations in the lipid profile between inflammatory bowel disease and healthy individuals were highlighted. Phosphatidylcholines, lyso-phosphatidylcholines and fatty acids were significantly changed among pathological samples suggesting changes in phospholipase A2 and arachidonic acid metabolic pathways. Variations in the levels of cholesteryl esters and glycerophospholipids were also found. Furthermore, a decrease in amino acids levels suggests mucosal damage in inflammatory bowel disease. CONCLUSIONS: Given good statistical results and predictive power of the model produced in our study, metabolomics can be considered as a valid tool to investigate inflammatory bowel disease.

Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract of uncertain origin, which includes ulcerative colitis (UC) and Crohn's disease (CD). The composition of gut microbiota may change in IBD affected individuals, but whether dysbiosis is the cause or the consequence of inflammatory processes in the intestinal tissue is still unclear. Here, the composition of the microbiota and the metabolites in stool of 183 subjects (82 UC, 50 CD, and 51 healthy controls) were determined. The metabolites content and the microbiological profiles were significantly different between IBD and healthy subjects. In the IBD group, Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria were significantly increased, whereas Bacteroidetes and Cyanobacteria were decreased. At genus level Escherichia, Faecalibacterium, Streptococcus, Sutterella and Veillonella were increased, whereas Bacteroides, Flavobacterium, and Oscillospira decreased. Various metabolites including biogenic amines, amino acids, lipids, were significantly increased in IBD, while others, such as two B group vitamins, were decreased in IBD compared to healthy subjects. This study underlines the potential role of an inter-omics approach in understanding the metabolic pathways involved in IBD. The combined evaluation of metabolites and fecal microbiome can be useful to discriminate between healthy subjects and patients with IBD.

Metabolomics analysis and modeling suggest a lysophosphocholines-PAF receptor interaction in fibromyalgia.

Fibromyalgia Syndrome (FMS) is a chronic disease characterized by widespread pain, and difficult to diagnose and treat. We analyzed the plasma metabolic profile of patients with FMS by using a metabolomics approach combining Liquid Chromatography-Quadrupole-Time Of Flight/Mass Spectrometry (LC-Q-TOF/MS) with multivariate statistical analysis, aiming to discriminate patients and controls. LC-Q-TOF/MS analysis of plasma (FMS patients: n = 22 and controls: n = 21) identified many lipid compounds, mainly lysophosphocholines (lysoPCs), phosphocholines and ceramides. Multivariate statistical analysis was performed to identify the discriminating metabolites. A protein docking and molecular dynamic (MD) study was then performed, using the most discriminating lysoPCs, to validate the binding to Platelet Activating Factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) Receptor (PAFr). Discriminating metabolites between FMS patients and controls were identified as 1-tetradecanoyl-sn-glycero-3-phosphocholine [PC(14:0/0:0)] and 1-hexadecanoyl-sn-glycero-3-phosphocholine [PC(16:0/0:0)]. MD and docking indicate that the ligands investigated have similar potentialities to activate the PAFr receptor. The application of a metabolomic approach discriminated FMS patients from controls, with an over-representation of PC(14:0/0:0) and PC(16:0/0:0) compounds in the metabolic profiles. These results and the modeling of metabolite-PAFr interaction, allowed us to hypothesize that lipids oxidative fragmentation might generate lysoPCs in abundance, that in turn will act as PAF-like bioactivators. Overall results suggest disease biomarkers and potential therapeutical targets for FMS.

Metabolomics explained to perinatologists and pediatricians.

Metabolomics is a new approach based on the systematic study of the full complement of low-molecular weight compounds (e.g. sugars, lipids, hormones, vitamins, secondary metabolites), both endogenous and exogenous, found within a cell, tissue, biofluid or organism. In order to avoid false expectation by using a metabolomics approach, it is important to have: (i) a properly planned design of the study based on a clear question to be answered, (ii) an appropriate knowledge of the equipments available; (iii) a proper statistical analysis and support and (iv) a validation of the results obtained. In the present short-review, these topics will be briefly described.