Can the FUT2 non-secretor phenotype associated with gut microbiota increase the children susceptibility for type 1 diabetes? A mini review

The global toll of type 1 diabetes (T1D) has steadily increased over the last decades. It is now widely acknowledged that T1D pathophysiology is more complex than expected. Indeed, a multifaceted interplay between genetic, metabolic, inflammatory and environmental factors exists that leads to heterogeneous clinical manifestations across individuals. Children with non-secretor phenotype and those affected by T1D share low abundance of bifidobacteria, low content of short-chain fatty acids, intestinal phosphatase alkaline and a high incidence of inflammatory bowel diseases. In this context, host-gut microbiota dyad may represent a relevant contributor to T1D development and progression due to its crucial role in shaping host immunity and susceptibility to autoimmune conditions. The FUT2 gene is responsible for the composition and functional properties of glycans in mucosal tissues and bodily secretions, including human milk. FUT2 polymorphisms may profoundly influence gut microbiota composition and host susceptibility to viral infections and chronic inflammatory disease. In this minireview, the possible interplay between mothers’phenotype, host FUT2 genetic background and gut microbiota composition will be discussed in perspective of the T1D onset. The study of FUT2-gut microbiota interaction may add a new piece on the puzzling T1D etiology and unveil novel targets of intervention to contrast T1D development and progression. Dietary interventions, including the intake of a-(1, 2)-fucosyl oligosaccharides in formula milk and the use of specific prebiotics and probiotics, could be hypothesized

Landfill fire impact on bee health. Beneficial effect of dietary supplementation with medicinal plants and probiotics in reducing oxidative stress and metal accumulation

The honey bee is an important pollinator insect susceptible to environmental contaminants. We investigated the effects of a waste fire event on elemental content, oxidative stress, and metabolic response in bees fed different nutrients (probiotics, Quassia amara, and placebo). The level of the elements was also investigated in honey and beeswax. Our data show a general increase in elemental concentrations in all bee groups after the event; however, the administration of probiotics and Quassia amara help fight oxidative stress in bees. Significantly lower concentrations of Ni, S, and U for honey in the probiotic group and a general and significant decrease in elemental concentrations for beeswax in the probiotic group and Li in the Quassia amara group were observed after the fire waste event. The comparison of the metabolic profiles through pre- and post-event PCA analyses showed that bees treated with different feeds react differently to the environmental event. The greatest differences in metabolic profiles are observed between the placebo-fed bees compared to the others. This study can help to understand how some stress factors can affect the health of bees and to take measures to protect these precious insects

NMR-based metabolomics for investigating urinary profiles of metal carpentry workers exposed to welding fumes and volatile organic compounds

IntroductionMetal carpentry includes a wide range of work activities such as welding and cutting metallic components, use of solvents and paints. Therefore, the employees in these types of activities are mainly exposed to welding fumes and volatile organic solvents. Here, we present an NMR-based metabolomic approach for assessing urinary profiles of workers in the same company that are exposed to two different risk factors.MethodsThe study enrolled 40 male subjects exposed to welding fumes, 13 male subjects exposed to volatile organic compounds of a metal carpentry company, and 24 healthy volunteers. All samples were collected, in the middle of the working week at fast. Thirty-five urinary metabolites belonging to different chemical classes such as amino acids, organic acids and amines were identified and quantified. Results were processed by multivariate statistical analysis for identifying significant metabolites for each working group examined, compared to controls.ResultsWorkers exposed to welding fumes displayed urinary increase in glutamine, tyrosine, taurine, creatine, methylguanidine and pseudouridine associated to oxidative impairment, while workers exposed to volatile organic compounds showed higher urinary levels of branched chain aminoacids.ConclusionOur work identified specific urinary profile related to each occupational exposure, even if it is below the threshold limit values

Antibiotics treatment promotes vasculogenesis in the brain of glioma-bearing mice

In recent years, several studies described the close relationship between the composition of gut microbiota and brain functions, highlighting the importance of gut-derived metabolites in mediating neuronal and glial cells cross-talk in physiological and pathological condition. Gut dysbiosis may affects cerebral tumors growth and progression, but the specific metabolites involved in this modulation have not been identified yet. Using a syngeneic mouse model of glioma, we have investigated the role of dysbiosis induced by the administration of non-absorbable antibiotics on mouse metabolome and on tumor microenvironment. We report that antibiotics treatment induced: (1) alteration of the gut and brain metabolome profiles; (2) modeling of tumor microenvironment toward a pro-angiogenic phenotype in which microglia and glioma cells are actively involved; (3) increased glioma stemness; (4) trans-differentiation of glioma cells into endothelial precursor cells, thus increasing vasculogenesis. We propose glycine as a metabolite that, in ABX-induced dysbiosis, shapes brain microenvironment and contributes to glioma growth and progression

Hyperbaric exposure and oxidative Stress in occupational activities (HEOxS): the study protocol

Background: Hyperbaric exposure (HE) is proven to be a stressor to several mechanisms in living cells. Even if after homeostasis restoration, harmful effects are expected, in particular a presence of free radicals. These latter are the stimulus to negative phenomenon as inflammation or cancer. In Italy, with 7500 km of sea shores, a large quantity of workers is exposed to HE during occupational activities. A deep knowledge of HE and bodily effects is not well defined; hence a multidisciplinary assessment of risk is needed. To detect one or more indicators of HE a research group is organised, under the INAIL sponsorship. The research project focused on the oxidative stress (OxS) and this paper details on the possible protocol to estimate, with a large amount of techniques on several human liquids, the relationship between OxS and HE. Specific attention will be paid to identify confounding factors and their influence. Methods: Blood and urine will be sampled. Several lab techniques will be performed on samples, both targeted, to measure the level of well-known biomarkers, and untargeted. Regard the formers: products of oxidation of DNA and RNA in urine; inflammation and temperature cytokines and protein carbonyles in blood. Untargeted evaluation will be performed for a metabolomics analysis in urine. Confounding factors: temperature, body fat, fitness, allergies and dietary habits. These factors will be assessed, directly or indirectly, prior and after HE. The final scope of the project is to determine one or more indicators that relates to HE in hits twofold nature: depth and duration. Conclusion: The relationship between OxS and HE is not deeply investigated and literature proposes diverging results. The project aims to define the time dependence of biomarkers related to OxS, to rise knowledge in risk assessment in workers exposed to HE

Metabolites

An altered amino acid metabolism has been described in frail older adults which may contribute to muscle loss and functional decline associated with frailty. In the present investigation, we compared circulating amino acid profiles of older adults with physical frailty and sarcopenia (PF&S, = 94), frail/pre-frail older adults with type 2 diabetes mellitus (F-T2DM, = 66), and robust non-diabetic controls ( = 40). Partial least squares discriminant analysis (PLS-DA) models were built to define the amino acid signatures associated with the different frailty phenotypes. PLS-DA allowed correct classification of participants with 78.2 ± 1.9% accuracy. Older adults with F-T2DM showed an amino acid profile characterized by higher levels of 3-methylhistidine, alanine, arginine, ethanolamine, and glutamic acid. PF&S and control participants were discriminated based on serum concentrations of aminoadipic acid, aspartate, citrulline, cystine, taurine, and tryptophan. These findings suggest that different types of frailty may be characterized by distinct metabolic perturbations. Amino acid profiling may therefore serve as a valuable tool for frailty biomarker discovery

“Insights in the electro-fermentation process with 13C-labelled experiments supported by NMR spectroscopy analysis”

The electro-fermentation (EF) process is an interesting and promising approach to control the spectrum of products deriving from microbial anaerobic fermentations, in terms of both composition and concentration. In EF a polarized electrode, functioning either as an anode [1] or a cathode [2], is used to modify the intracellular redox balance so as to redirect the carbon flux towards the desired end-products. To date, however, it is still not clear whether an electron transfer between microorganisms and the electrode is involved or if the process is simply triggered by a change in the oxidation-reduction potential of the reaction medium. Here, in order to gain a deeper understanding on the effect of the polarized electrode on the microbial metabolism, EF experiments have been performed by supplying 13C-labelled glucose, along with ethanol and acetate, to anaerobic mixed cultures inoculated at the cathode chamber of H-type reactors with the electrode potential controlled at -0.70 V (vs. SHE). The fermentation pattern has been tracked over time with the nuclear magnetic resonance (NMR) spectroscopy, that is the elective technique for 13C-labelled analysis. Parallel control tests (under identical conditions but in the absence of electrode polarization) have been carried out and compared to EF experiments

Approccio metabolomico per la caratterizzazione del profilo urinario di lavoratori esposti in un’industria del comparto metallurgico tramite spettroscopia NMR: uno studio pilota.

Introduzione Il comparto industriale della carpenteria metallica prevede mansioni di impiego come cui taglio, piegatura, saldatura, verniciatura e zincatura di semilavorati metallici. Pertanto, i lavoratori operanti in tale settore risultano potenzialmente esposti a differenti categorie di sostanze pericolose: dai fumi di saldatura ai composti organici volatili (VOC). A tal riguardo lo scopo di questo studio è stato quello di valutare il profilo metabolomico urinario di lavoratori impiegati in differenti settori di un’azienda ponendolo in relazione con i complessi scenari di esposizione possibili. La ricerca ha coinvolto 40 soggetti del comparto saldature e 13 soggetti del comparto verniciatura; in confronto con 24 volontari sani esterni all’azienda costituenti il gruppo di controllo. Materiali e Metodi Da ciascun campione di urina, raccolto nel mezzo della settimana al termine del turno lavorativo, è stata prelevata un’aliquota di 1200 µL. I campioni sono stati centrifugati a 11,000 rpm per 15 min ad una temperatura di 4°C, successivamente a 1000 µL di surnatante sono stati aggiunti 100 µL di TSP (acido 3- trimetilsilil-propionico-2,2,3,3-d4) come standard interno, ed il pH è stato portato a pH 7 attraverso piccole aggiunte di NaOH o HCl. Infine 700 µL del campione sono stati trasferiti in cryovials e conservati a -80°C fino al giorno dell’analisi tramite spettroscopia di risonanza magnetica nucleare (NMR). Per ciascun campione è stato registrato lo spettro monodimensionale del protone ( 1 H-NMR) in aggiunta ad esperimenti bidimensionali di tipo omonucleare 1 H- 1 H (TOCSY), ed eteronucleare 1 H- 13 C (HSQC, HMBC). Risultati e discussione Dall’analisi degli spettri sono stati identificati e quantificati 35 metaboliti appartenenti a differenti classi chimiche quali acidi organici, amminoacidi lineari e ramificati ed ammine. Sulla matrice dei dati ottenuti in concentrazione e normalizzati per i valori di Creatinina urinaria, è stata poi effettuata un’analisi statistica multivariata, tramite la realizzazione di modelli PLS (Partial Least Squares regression), ed univariata allo scopo di individuare i metaboliti significativi per ciascun gruppo di lavoratori rispetto al gruppo di controllo. I profili metabolici caratterizzanti ciascuno dei due gruppi di lavoratori reclutati, risultano analoghi: le concentrazioni urinarie di metaboliti appartenenti ai pathways di purine (Ipoxantina) e pirimidine (Pseudouridina) così come quelli coinvolti nel pathway della Glicina-Serina-Treonina (glicina, taurina, colina) sono significativamente più alti nei lavoratori rispetto ai controlli. In accordo con dati di letteratura [1] tale aumento può essere correlato ad un incremento di specie reattive dell’ossigeno (ROS) mediatrici di danno ossidativo a carico dell’organismo e conseguenza diretta dell’esposizione. In aggiunta, al danno ossidativo, può essere collegato anche l’incremento della concentrazione di Metilguanidina, metabolita sintetizzato nei perossisomi epatici, e spesso associato al danno tissutale; nonché di creatina, essendo i ROS responsabili dell’inibizione dell’enzima creatin-chinasi, coinvolto nella trasformazione della creatina in creatinina. Conclusioni Nonostante si tratti di uno studio pilota, l’analisi effettuata mette in luce l’alterazione di diversi pathways metabolici nei lavoratori rispetto al gruppo di controllo suggerendo una probabile influenza dell’esposizione sul metabolismo epatico. L’approccio metabolomico descritto è dunque in grado di fornire informazioni utili su alterazioni metaboliche nel caso di esposizione a miscele complesse anche quando l’esposizione è ben al di sotto dei valori limite di soglia imposti dalla vigente legislatura