An investigation into the temporal reproducibility of Tryptophan metabolite networks among healthy adolescents

Tryptophan and its bioactive metabolites are associated with health conditions such as systemic inflammation, cardiometabolic diseases, and neurodegenerative disorders. There are dynamic interactions among metabolites of tryptophan. The interactions between metabolites, particularly those that are strong and temporally reproducible could be of pathophysiological relevance. Using a targeted metabolomics approach, the concentration levels of tryptophan and 18 of its metabolites across multiple pathways was quantified in 24-hours urine samples at 2 time-points, age 17 years (baseline) and 18 years (follow-up) from 132 (52% female) apparently healthy adolescent participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. In sex-specific analyses, we applied 2 network approaches, the Gaussian graphical model and Bayesian network to (1) explore the network structure for both time-points, (2) retrieve strongly related metabolites, and (3) determine whether the strongly related metabolites were temporally reproducible. Independent of selected covariates, the 2 network approaches revealed 5 associations that were strong and temporally reproducible. These were novel relationships, between kynurenic acid and indole-3-acetic acid in females and between kynurenic acid and xanthurenic acid in males, as well as known relationships between kynurenine and 3-hydroxykynurenine, and between 3-hydroxykynurenine and 3-hydroxyanthranilic acid in females and between tryptophan and kynurenine in males. Overall, this epidemiological study using network-based approaches shed new light into tryptophan metabolism, particularly the interaction of host and microbial metabolites. The 5 observed relationships suggested the existence of a temporally stable pattern of tryptophan and 6 metabolites in healthy adolescent, which could be further investigated in search of fingerprints of specific physiological states. The metabolites in these relationships may represent a multi-biomarker panel that could be informative for health outcome

Discrimination of monovarietal Italian red wines using derivative voltammetry

Identification of specific analytical fingerprints associated to grape variety, origin, or vintage is of great interest for wine producers, regulatory agencies, and consumers. However, assessing such varietal fingerprint is complex, time consuming, and requires expensive analytical techniques. Voltammetry is a fast, cheap, and user-friendly analytical tool that has been used to investigate and measure wine phenolics

Use of Untargeted Liquid Chromatography\u2013Mass Spectrometry Metabolome To Discriminate Italian Monovarietal Red Wines, Produced in Their Different Terroirs

The aim of this project was to register, in a liquid chromatography\u2013mass spectrometry-based untargeted single-batch analysis, the metabolome of 11 single-cultivar, single-vintage Italian red wines (Aglianico, Cannonau, Corvina, Montepulciano, Nebbiolo, Nerello, Primitivo, Raboso, Sagrantino, Sangiovese, and Teroldego) from 12 regions across Italy, each one produced in their terroirs under ad hoc legal frameworks to guarantee their quality and origin. The data provided indications regarding the similarity between the cultivars and highlighted a rich list of putative biomarkers of origin wines (pBOWs) characterizing each individual cultivar\u2013terroir combination, where Primitivo, Teroldego, and Nebbiolo had the maximum number of unique pBOWs. The pBOWs included anthocyanins (Teroldego), flavanols (Aglianico, Sangiovese, Nerello, and Nebbiolo), amino acids and N-containing metabolites (Primitivo), hydroxycinnamates (Cannonau), and flavonols (Sangiovese). The raw data generated in this study are publicly available and, therefore, accessible and reusable as a baseline data set for future investigations

Quantification of Urinary Phenyl-γ-Valerolactones and Related Valeric Acids in Human Urine on Consumption of Apples

Flavan-3-ols are dietary bioactive molecules that have beneficial effects on human health and reduce the risk of various diseases. Monomeric flavan-3-ols are rapidly absorbed in the small intestine and released in the blood stream as phase II conjugates. Polymeric flavan-3-ols are extensively metabolized by colonic gut microbiota into phenyl-γ-valerolactones and their related phenylvaleric acids. These molecules are the main circulating metabolites in humans after the ingestion of flavan-3-ol rich-products; nevertheless, they have received less attention and their role is not understood yet. Here, we describe the quantification of 8 phenyl-γ-valerolactones and 3 phenylvaleric acids in the urine of 11 subjects on consumption of apples by using UHPLC-ESI-Triple Quad-MS with pure reference compounds. Phenyl-γ-valerolactones, mainly as sulfate and glucuronic acid conjugates, reached maximum excretion between 6 and 12 after apple consumption, with a decline thereafter. Significant differences were detected in the cumulative excretion rates within subjects and in the ratio of dihydroxyphenyl-γ-valerolactone sulfate to glucuronide conjugates. This work observed for the first time the presence of two distinct metabotypes with regards to the excretion of phenyl-γ-valerolactone phase II conjugates

Metabolomic workflow for the accurate and high-throughput exploration of the pathways of tryptophan, tyrosine, phenylalanine, and branched-chain amino acids in human biofluids

10openInternationalInternational coauthor/editorThe modulation of host and dietary metabolites by gut microbiota (GM) is important for maintaining correct host physiology and in the onset of various pathologies. An ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the targeted quantitation in human plasma, serum, and urine of 89 metabolites resulting from human-GM cometabolism of dietary essential amino acids tryptophan, tyrosine, and phenylalanine as well as branched-chain amino acids. Ninety-six-well plate hybrid-SPE enables fast clean-up of plasma and serum. Urine was diluted and filtered. A 15 min cycle enabled the acquisition of 96 samples per day, with most of the metabolites stable in aqueous solution for up to 72 h. Calibration curves were specifically optimized to cover expected concentrations in biological fluids, and limits of detection were at the order of ppb. Matrix effects were in acceptable ranges, and analytical recoveries were in general greater than 80%. Inter and intraday precision and accuracy were satisfactory. We demonstrated its application in plasma and urine samples obtained from the same individual in the frame of an interventional study, allowing the quantitation of 51 metabolites. The method could be considered the reference for deciphering changes in human-gut microbial cometabolism in health and disease. Data are available via Metabolights with the identifier MTBLS4399.openAnesi, Andrea; Berding, Kirsten; Clarke, Gerard; Stanton, Catherine; Cryan, John F.; Caplice, Noel; Ross, R. Paul; Doolan, Andrea; Vrhovsek, Urska; Mattivi, FulvioAnesi, A.; Berding, K.; Clarke, G.; Stanton, C.; Cryan, J.F.; Caplice, N.; Ross, R.P.; Doolan, A.; Vrhovsek, U.; Mattivi, F

Phenolic extraction and mechanical properties of skins and seeds during maceration of four main italian red wine grape varieties

Red grape varieties are characterized by different phenolic contents (prominently tannins and anthocyanins) found in skins and seeds. The extractability of these compounds varies during maceration, as well as the mechanical properties of skins and seeds. Four main Italian red winegrape varieties were tested to understand these differences during a simulated maceration process

The macromolecular diversity of Italian monovarietal red wines

13openInternationalItalian coauthor/editorWhile red wine phenolics have been extensively studied, polysaccharides and proteins have not received the same level of attention, especially when considering Italian wines. In this study, for the first time, quantitative and qualitative data on the macromolecular (proteins and polysaccharides) and tannin composition of 110 monovarietal red wines from 11 of the most important Italian grape varieties are reported. The winemaking did not include any filtration, oak contact, fining treatments, or ageing on yeast lees. Results highlighted a great inter- and intra- varietal diversity. The protein content ranged between 0 and 159 mg/L, polysaccharides between 211 and 1081 mg/L and total tannins between 171 and 3746 mg/L, with averages of 41 mg/L, 497 mg/L and 1687 mg/L, respectively. Six varieties with protein content representative of the variability observed were selected and submitted to electrophoresis. Within each variety, the SDS-PAGE mobility of protein-tannin complexes was similar but showed two distinct patterns for wines of different varieties (higher mobility for Corvina, Teroldego and Raboso Piave, lower mobility for Nebbiolo, Aglianico, Cannonau), suggesting that the Italian monovarietal wines can be diverse also in their colloidal-forming structures. This can be explained by looking at the different percentages of protein-reactive tannins (TBSA) on the total tannin content (TMCP), which is a varietal characteristicopenMarangon, Matteo; De Iseppi, Alberto; Gerbi, Vincenzo; Mattivi, Fulvio; Moio, Luigi; Piombino, Paola; Parpinello, Giuseppina Paola; Rolle, Luca; Slaghenaufi, Davide; Versari, Andrea; Vrhovsek, Urska; Ugliano, Maurizio; Curioni, AndreaMarangon, M.; De Iseppi, A.; Gerbi, V.; Mattivi, F.; Moio, L.; Piombino, P.; Parpinello, G.P.; Rolle, L.; Slaghenaufi, D.; Versari, A.; Vrhovsek, U.; Ugliano, M.; Curioni, A

Monoterpenoids and norisoprenoids in Italian red wines

This work aimed to investigate the occurrence of different monoterpenoids and norisoprenoids in 10 monovarietal Italian red wines (Aglianico, Cannonau, Corvina, Montepulciano, Nebbiolo, Nerello, Primitivo, Raboso, Sangiovese and Teroldego) from 12 regions across Italy. The wines were produced in their terroirs following the oenological practices and legislation of the respective appellation. Data showed that different wine varietals were characterised by peculiar profiles of monoterpenoids and norisoprenoids. Montepulciano and Cannonau wines showed highest levels of nerol, terpinolene, α-terpineol, limonene and of the norisoprenoids β-damascenone, α-ionone, TPB, TDN and vitispirane. Aglianico, Corvina, Nebbiolo and Primitivo were characterised by relatively high levels of linear monoterpene alcohols such as linalool and geraniol. Sangiovese samples from Tuscany could be differentiated from those of Romagna, with the former characterised by a higher content of α-terpinene and the latter of γ-terpinene. The monoterpene 1,4-cineole was present in Montepulciano, Raboso and Sangiovese at potentially relevant olfactory levels, its occurrence associated with higher content of terpinen-1-ol acting as a potential precursor under wine acid condition

Association between the indole pathway of tryptophan metabolism and subclinical depressive symptoms in obesity: a preliminary study

12partially_openInternationalInternational coauthor/editorConverging data support the role of chronic low-grade inflammation in depressive symptomatology in obesity. One mechanism likely to be involved relies on the effects of inflammation on tryptophan (TRP) metabolism. While recent data document alterations in the indole pathway of TRP metabolism in obesity, the relevance of this mechanism to obesity-related depressive symptoms has not been investigated. The aim of this preliminary study was to assess the association between plasma levels of TRP and indole metabolites and depressive symptoms in 44 subjects with severe or morbid obesity, free of clinically relevant neuropsychiatric disorders. The interaction effect of inflammation, reflected in serum high-sensitive C-reactive protein (hsCRP) levels, and indoles on depressive symptoms was also determined. Higher serum levels of hsCRP and lower concentrations of TRP and indoles, particularly indole-3-carboxaldehyde (IAld), correlated with more severe depressive symptoms. Interestingly, the effect of high hsCRP levels in predicting greater depressive symptoms was potentiated by low IAld levels. These results comfort the link between inflammation, the indole pathway of TRP metabolism, and obesity-related depressive symptomsmixedDelgado, Inês; Cussotto, Sofia; Anesi, Andrea; Dexpert, Sandra; Aubert, Agnès; Aouizerate, Bruno; Beau, Cédric; Forestier, Damien; Ledaguenel, Patrick; Magne, Eric; Mattivi, Fulvio; Capuron, LucileDelgado, I.; Cussotto, S.; Anesi, A.; Dexpert, S.; Aubert, A.; Aouizerate, B.; Beau, C.; Forestier, D.; Ledaguenel, P.; Magne, E.; Mattivi, F.; Capuron, L

Geomorphic flood hazard mapping: from floodplain delineation to flood hazard characterization

Recent studies show how geomorphic descriptors, retrieved from digital elevation models (DEMs), can be used for flood hazard mapping. As they strictly depend on the accuracy of the input DEMs and reference flood hazard maps used for training, DEM-based flood hazard models may display severe inconsistencies. Our study shows the application of two advanced DEM-based models to a large study area, and presents two main innovative points. First, the delicate tasks of appropriately selecting the input DEM and flood hazard map are specifically addressed with newly defined methods. Second, the ability of DEM-based models to exploit their natural features to enhance flood hazard mapping over the study region is investigated. Our results show (a) the benefits of considering multiple geomorphic descriptors, (b) the potential of DEM-based models for completing the information of imperfect reference flood hazard maps, and (c) the advantages of continuous representation of hazard over binary flood maps