Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.

BACKGROUND: Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide. METHODS: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed. RESULTS: Longer colonic transit was linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point. CONCLUSIONS: Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response syndrome.

Metabolomic Profiles Associated with Obesity and Periodontitis during Pregnancy: Cross-Sectional Study with Proton Nuclear Magnetic Resonance (1H-NMR)-Based Analysis.

This study aimed to elucidate the metabolomic signature associated with obesity and periodontitis during pregnancy in plasma and saliva biofluids. Ninety-eight pregnant women were divided into: with obesity and periodontitis (OP = 20), with obesity but without periodontitis (OWP = 27), with normal BMI but with periodontitis (NP = 21), with normal BMI and without periodontitis (NWP = 30). Saliva and plasma were analyzed by 1H-NMR for metabolites identification. Partial Least Squares-Discriminant Analysis (PLS-DA), Sparse PLS-DA (sPLS-DA), and Variable Importance of Projection (VIP) were performed. ANOVA and Pearson's correlation were applied (p < 0.05). Plasmatic analysis indicated the levels of glucose (p = 0.041) and phenylalanine (p = 0.015) were positively correlated with periodontal parameters and BMI, respectively. In saliva, periodontitis was mainly associated with high levels of acetic acid (p = 0.024), isovaleric acid, butyric acid, leucine, valine, isoleucine, and propionic acid (p < 0.001). High salivary concentrations of glycine (p = 0.015), succinic acid (p = 0.015), and lactate (p = 0.026) were associated with obesity. Saliva demonstrated a more elucidative difference than plasma, indicating the glucose-alanine cycle, alanine metabolism, valine, leucine and isoleucine degradation, glutamate metabolism, and Warburg effect as the main metabolic pathways.

Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in Salmonella enterica.

In Salmonella enterica, 2-aminoacrylate (2AA) is a reactive enamine intermediate generated during a number of biochemical reactions. When the 2-iminobutanoate/2-iminopropanoate deaminase (RidA; EC: 3.5.99.10) is eliminated, 2AA accumulates and inhibits the activity of multiple pyridoxal 5'-phosphate(PLP)-dependent enzymes. In this study, untargeted proton nuclear magnetic resonance (1H NMR) metabolomics and transcriptomics data were used to uncover the global metabolic response of S. enterica to the accumulation of 2AA. The data showed that elimination of RidA perturbed folate and branched chain amino acid metabolism. Many of the resulting perturbations were consistent with the known effect of 2AA stress, while other results suggested additional potential enzyme targets of 2AA-dependent damage. The majority of transcriptional and metabolic changes appeared to be the consequence of downstream effects on the metabolic network, since they were not directly attributable to a PLP-dependent enzyme. In total, the results highlighted the complexity of changes stemming from multiple perturbations of the metabolic network, and suggested hypotheses that will be valuable in future studies of the RidA paradigm of endogenous 2AA stress.

Ultrafast double-quantum NMR spectroscopy.

We demonstrate the acquisition of double-quantum NMR spectra in less than three seconds and illustrate the synergies between double-quantum and ultrafast NMR spectroscopy for the analysis of complex mixtures.

Evaluation of fast 2D NMR for metabolomics.

Two-dimensional nuclear magnetic resonance (2D NMR) is increasingly explored as a tool for metabolomics because of its superior resolution compared to one-dimensional NMR (1D NMR). However, 2D NMR is characterized by longer acquisition times, which makes it less suitable for high-throughput studies. In this Article, we evaluated two methods for the acceleration of nD NMR, ultrafast (UF) and nonuniform sampling (NUS), in the context of metabolomics. To this end, model samples mimicking the metabolic profile variations in serum from subjects affected by colorectal cancer and controls were analyzed by 1D (1)H NMR along with conventional and accelerated DQF-COSY and HSQC. A statistical analysis (OPLS-DA) yielded similar results for the group separation with all techniques, but biomarker identification from 2D spectra was substantially enhanced, both in terms of number of molecules and easiness of assignment. Most interestingly, fast 2D NMR techniques lead to similar results as conventional 2D NMR, opening the way for high-throughput metabolomics studies using 2D NMR.