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 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

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

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

Correction to: Scientific Reports https://doi.org/10.1038/s41598-017-10034-5, published online 25 August 2017

A metabolomic study of preterm human and formula milk by high resolution NMR and GC/MS analysis: preliminary results

OBJECTIVE: The aim of the present study was to investigate the metabolic profile of preterm human breast milk (HBM) by using a metabolomic approach. METHODS: NMR spectroscopy and GC/MS were used to analyze the water-soluble and lipid fractions extracted from milk samples obtained from mothers giving birth at 26-36 weeks of gestation. For the sake of comparison, preterm formula milk was also studied. RESULTS: The multivariate statistical analysis of the data evidenced biochemical variability both between preterm HBM and commercial milk and within the group of HBM samples. CONCLUSIONS: The preliminary results of this study suggest that metabolomics may provide a promising tool to study aspects related to the nutrition and health of preterm infant

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

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

BACKGROUND: Recent data suggest that imbalances in the composition of the gut microbiome (GM) could exacerbate the progression of Parkinson's Disease (PD). The effect of Levodopa (LD) has 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, in particular, LCIG on GM and metabolome. METHODS: Faecal DNA samples from 107 patients with clinical diagnosis of PD were analyzed by next-generation-sequencing of 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). Faecal metabolic extracts were evaluated by Gas Chromatography Mass Spectrometry (GC-MS). RESULTS: The multivariate analysis showed a significant higher abundance in the LCIG-Group of Enterobacteriaceae, Escherichia and Serratia compared to LD-Group. Compared to Naïve-Group, the univariate analysis showed a reduction of Blautia, Lachnospirae in 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 to a metabolic profile linked to gut inflammation. CONCLUSION: 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 microenviroment, potentially related to the PD state and progression

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.This study was funded by Agilent Technologies, Regione Autonoma della Sardegna (L.R.7/2007, Grant Number F71J12001180002), and the Medical Research Council UK (Grant Number MR/P011705/1)