The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called ‘First 1000 Days’) are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.

Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction. A 500 MHz proton nuclear magnetic resonance (1H-NMR)-based analysis was performed on blood samples from three groups of individuals: 9 control subjects (Group A), 9 HF patients with mild to moderate impairment of left ventricle ejection fraction (LVEF: 41.9 ± 4.0 %; Group B), and 15 HF patients with severe LVEF impairment (25.3 ± 10.3 %; Group C). In order to create a descriptive model of HF, a supervised orthogonal projection on latent structures discriminant analysis (OPLS-DA) was applied using speckle tracking-derived longitudinal strain rate as the Y-variable in the multivariate analysis. OPLS-DA identified three metabolic clusters related to the studied groups achieving good values for R2 [R2(X) = 0.64; R2(Y) = 0.59] and Q2 (0.39). The most important metabolites implicated in the clustering were 2-hydroxybutyrate, glycine, methylmalonate, and myo-inositol. The results demonstrate the suitability of metabolomics in combination with functional evaluation techniques in HF staging. This innovative tool should facilitate investigation of perturbed metabolic pathways in HF and their correlation with the impairment of myocardial function.

Several differential panels of metabolites have been associated with the presence of metabolic syndrome and its related conditions, namely non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). This study aimed to perform a systematic review to summarize the most recent finding in terms of circulating biomarkers following NAFLD/NASH syndromes. Hence, the research was focused on NAFLD/NASH studies analysed by metabolomics approaches. Following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, a systematic search was conducted on the PubMed database. The inclusion criteria were (i) publication date between 2010 and 2021, (ii) presence of the combination of terms: metabolomics and NAFLD/NASH, and (iii) published in a scholarly peer-reviewed journal. Studies were excluded from the review if they were (i) single-case studies, (ii) unpublished thesis and dissertation studies, and (iii) not published in a peer-reviewed journal. Following these procedures, 10 eligible studies among 93 were taken into consideration. The metabolisms of amino acids, fatty acid, and vitamins were significantly different in patients affected by NAFLD and NASH compared to healthy controls. These findings suggest that low weight metabolites are an important indicator for NAFLD/NASH syndrome and there is a strong overlap between NAFLD/NASH and the metabolic syndrome. These findings may lead to new perspectives in early diagnosis, identification of novel biomarkers, and providing novel targets for pharmacological interventions.

Urinary tract infection (UTI) is one of the most common diagnoses in girls and women, and to a lesser extent in boys and men younger than 50 years. Escherichia coli, followed by Klebsiella spp. and Proteus spp., cause 75-90% of all infections. Infection of the urinary tract is identified by growth of a significant number of a single species in the urine, in the presence of symptoms. Urinary culture is an accurate diagnostic method but takes several hours or days to be carried out. Metabolomics analysis aims to identify biomarkers that are capable of speeding up diagnosis. Urine samples from 51 patients with a prior diagnosis of Escherichia coli-associated UTI, from 21 patients with UTI caused by other pathogens (bacteria and fungi), and from 61 healthy controls were analyzed. The 1H-NMR spectra were acquired and processed. Multivariate statistical models were applied and their performance was validated using permutation test and ROC curve. Orthogonal Partial Least Squares-discriminant Analysis (OPLS-DA) showed good separation (R2Y = 0.76, Q2=0.45, p < 0.001) between UTI caused by Escherichia coli and healthy controls. Acetate and trimethylamine were identified as discriminant metabolites. The concentrations of both metabolites were calculated and used to build the ROC curves. The discriminant metabolites identified were also evaluated in urine samples from patients with other pathogens infections to test their specificity. Acetate and trimethylamine were identified as optimal candidates for biomarkers for UTI diagnosis. The conclusions support the possibility of a fast diagnostic test for Escherichia coli-associated UTI using acetate and trimethylamine concentrations.

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.

Cancer cells adjust their metabolism to meet energy demands. In particular, glutamine addiction represents a distinctive feature of several types of tumors, including colorectal cancer. In this study, four colorectal cancer cell lines (Caco-2, HCT116, HT29 and SW480) were cultured with or without glutamine. The growth and proliferation rate, colony-forming capacity, apoptosis, cell cycle, redox homeostasis and metabolomic analysis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, high-performance liquid chromatography and gas chromatography/mass spectrometry techniques. The results show that glutamine represents an important metabolite for cell growth and that its deprivation reduces the proliferation of colorectal cancer cells. Glutamine depletion induces cell death and cell cycle arrest in the GO/G1 phase by modulating energy metabolism, the amino acid content and antioxidant defenses. Moreover, the combined glutamine starvation with the glycolysis inhibitor 2-deoxy-D-glucose exerted a stronger cytotoxic effect. This study offers a strong rationale for targeting glutamine metabolism alone or in combination with glucose metabolism to achieve a therapeutic benefit in the treatment of colon cancer.