The fascinating theory of fetal programming of adult diseases: A review of the fundamentals of the Barker hypothesis.

The theory of fetal programming of adult diseases was first proposed by David J.P. Barker in the eighties of the previous century, to explain the higher susceptibility of some people toward the development of ischemic heart disease. According to his hypothesis, poor maternal living conditions during gestation represent an important risk factor for the onset of atherosclerotic heart disease later in life. The analysis of the early phases of fetal development is a fundamental tool for the risk stratification of children and adults, allowing the identification of susceptible or resistant subjects to multiple diseases later in life. Here, we provide a narrative summary of the most relevant evidence supporting the Barker hypothesis in multiple fields of medicine, including neuropsychiatric disorders, such as Parkinson disease and Alzheimer disease, kidney failure, atherosclerosis, coronary heart disease, stroke, diabetes, cancer onset and progression, metabolic syndrome, and infectious diseases including COVID-19. Given the consensus on the role of body weight at birth as a practical indicator of the fetal nutritional status during gestation, every subject with a low birth weight should be considered an "at risk" subject for the development of multiple diseases later in life. The hypothesis of the "physiological regenerative medicine," able to improve fetal organs' development in the perinatal period is discussed, in the light of recent experimental data indicating Thymosin Beta-4 as a powerful growth promoter when administered to pregnant mothers before birth.

Clinical Efficacy and Metabolomics Modifications Induced by Polyphenol Compound Supplementation in the Treatment of Residual Dizziness following Semont Maneuver in Benign Paroxysmal Positional Vertigo (BPPV) of the Posterior Semicircular Canal (PSC): Preliminary Results.

Benign paroxysmal positional vertigo (BPPV) represents the most frequent cause of peripheral vertigo. In most cases, it is successfully treated using the canalith repositioning procedure, but it is often followed by continuous lightheadedness in the absence of vertigo or nystagmus (residual dizziness, RD). Our aim is to describe the clinical effectiveness and the urine metabolomics profile of treating these patients with polyphenol compound supplementation. We enrolled 30 patients reporting RD after BPPV of the posterior semicircular canal (PSC) successfully treated using the Semont maneuver. Supplementation with a polyphenol compound was administered for 60 days, and patients were evaluated after 30 and 60 days of treatment using self-administered questionnaires (Visual Analog Scales for Dizziness and Nausea, Dizziness Handicap Inventory, DHI) and urine metabolomics analysis performed using 1H-NMR spectroscopy and multivariate followed by univariate analysis. Most patients reported excellent or good efficacy in the treatment of RD with a significant decrease in VAS and DHI values. The metabolomics analysis identified six significant metabolites related to the treatment, namely 1-methylnicotinamide, anserine, hippurate, lysine, methyl succinate and urea, indicating the inflammatory activities and antioxidant properties of the polyphenol compound. These preliminary data suggest that supplementation with a polyphenol compound could induce some metabolic changes that can help in recovery from RD. However, future steps will require confirmation with a more significant cohort of patients and an extension of the metabolomics evaluation to other problems concerning the different clinical aspects of BPPV, such as the high rate of relapse.

Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder.

The evolving field of multi-omics combines data and provides methods for simultaneous analysis across several omics levels. Here, we integrated genomics (transmitted and non-transmitted polygenic scores [PGSs]), epigenomics, and metabolomics data in a multi-omics framework to identify biomarkers for Attention-Deficit/Hyperactivity Disorder (ADHD) and investigated the connections among the three omics levels. We first trained single- and next multi-omics models to differentiate between cases and controls in 596 twins (cases = 14.8%) from the Netherlands Twin Register (NTR) demonstrating reasonable in-sample prediction through cross-validation. The multi-omics model selected 30 PGSs, 143 CpGs, and 90 metabolites. We confirmed previous associations of ADHD with glucocorticoid exposure and the transmembrane protein family TMEM, show that the DNA methylation of the MAD1L1 gene associated with ADHD has a relation with parental smoking behavior, and present novel findings including associations between indirect genetic effects and CpGs of the STAP2 gene. However, out-of-sample prediction in NTR participants (N = 258, cases = 14.3%) and in a clinical sample (N = 145, cases = 51%) did not perform well (range misclassification was [0.40, 0.57]). The results highlighted connections between omics levels, with the strongest connections between non-transmitted PGSs, CpGs, and amino acid levels and show that multi-omics designs considering interrelated omics levels can help unravel the complex biology underlying ADHD.

Metabolomics of head and neck cancer in biofluids: an integrative systematic review.

INTRODUCTION: Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC. OBJECTIVES: To summarize and consolidate the available evidence on metabolomics and HNC in plasma/serum, saliva, and urine. METHODS: A systematic search of experimental research was executed using PubMed and Web of Science. Available data on areas under the curve was extracted. Metabolic pathway enrichment analysis were performed to identify metabolic pathways altered in HNC. Fifty-four studies were eligible for data extraction (33 performed in plasma/serum, 15 in saliva and 6 in urine). RESULTS: Metabolites with high discriminatory performance for detection of HNC included single metabolites and combination panels of several lysoPCs, pyroglutamate, glutamic acid, glucose, tartronic acid, arachidonic acid, norvaline, linoleic acid, propionate, acetone, acetate, choline, glutamate and others. The glucose-alanine cycle and the urea cycle were the most altered pathways in HNC, among other pathways (i.e. gluconeogenesis, glycine and serine metabolism, alanine metabolism, etc.). Specific metabolites that can potentially serve as complementary less- or non-invasive biomarkers, as well as metabolic pathways integrating the data from the available studies, are presented. CONCLUSION: The present work highlights utility of metabolite-based biomarkers for risk assessment, early detection, and prognostication of HNC, as well as facilitates incorporation of available metabolomics studies into multi-omics data integration and big data analytics for personalized health.

Gas Chromatography-Mass Spectrometry (GC-MS) Metabolites Analysis in Endometriosis Patients: A Prospective Observational Translational Study.

BACKGROUND: Endometriosis affects women of reproductive age, and its pathogenesis is still unclear. Typically, it overlaps other similar medical and surgical conditions, determining a delay in early diagnosis. Metabolomics allows studying metabolic changes in different physiological or pathological states to discover new potential biomarkers. We used the gas chromatography-mass spectrometer (GC-MS) to explore metabolic alterations in endometriosis to better understand its pathophysiology and find new biomarkers. METHODS: Twenty-two serum samples of patients with symptomatic endometriosis and ten without it were collected and subjected to GC-MS analysis. Multivariate and univariate statistical analyses were performed, followed by pathway analysis. RESULTS: Partial least squares discriminant analysis was performed to determine the differences between the two groups (p = 0.003). Threonic acid, 3-hydroxybutyric acid, and proline increased significantly in endometriosis patients, while alanine and valine decreased. ROC curves were built to test the diagnostic power of metabolites. The pathway analysis identified the synthesis and degradation of ketone bodies and the biosynthesis of phenylalanine, tyrosine, and tryptophan as the most altered pathways. CONCLUSIONS: The metabolomic approach identifies metabolic alterations in women with endometriosis. These findings may improve our understanding of the pathophysiological mechanisms of disease and the discovery of new biomarkers.

The kidney in COVID-19: protagonist or figurant?

The etiology of injury in COVID-19 patients is diverse and multifactorial. Autopsy and biopsy studies reveal, alongside podocyte and tubular cell anomalies, the presence of virion within the cells. Evidence suggests that, in addition to the direct cytopathic effect of SARS-CoV-2 on the glomeruli and renal tubules, there is also the indirect effect of cell-mediated immunity, the cytokines storm and the cross-talk between organs with possible systemic effects of the disease. These mechanisms are interconnected and have profound therapeutic implications involving extracorporeal removal of inflammatory cytokines. Dialysis patients, and children, in particular, should be classified as "at high risk" of contracting the disease. Infections are one of the most frequent causes of death in children with chronic renal failure who undergo dialysis. The reasons for this particular susceptibility are to be found in the compromised immune system, secondary to chronic malnutrition, immunosuppressive therapy, and uremia, frequent contact with healthcare personnel and other patients attending the dialysis unit and in need of the presence of other family members during treatment.

Integrative Multi-omics Analysis of Childhood Aggressive Behavior.

This study introduces and illustrates the potential of an integrated multi-omics approach in investigating the underlying biology of complex traits such as childhood aggressive behavior. In 645 twins (cases = 42%), we trained single- and integrative multi-omics models to identify biomarkers for subclinical aggression and investigated the connections among these biomarkers. Our data comprised transmitted and two non-transmitted polygenic scores (PGSs) for 15 traits, 78,772 CpGs, and 90 metabolites. The single-omics models selected 31 PGSs, 1614 CpGs, and 90 metabolites, and the multi-omics model comprised 44 PGSs, 746 CpGs, and 90 metabolites. The predictive accuracy for these models in the test (N = 277, cases = 42%) and independent clinical data (N = 142, cases = 45%) ranged from 43 to 57%. We observed strong connections between DNA methylation, amino acids, and parental non-transmitted PGSs for ADHD, Autism Spectrum Disorder, intelligence, smoking initiation, and self-reported health. Aggression-related omics traits link to known and novel risk factors, including inflammation, carcinogens, and smoking.

Familial Hypercholesterolaemia in Children and Adolescents: Current and Future Perspectives.

Familial hypercholesterolemia (FH) is a genetic disease, the underlying cause of which is represented by mutations capable of influencing the metabolism of low-density lipoproteins (LDL). The distinguishing characteristic of FH has increased LDL cholesterol blood levels since birth, triggering early development of atherosclerosis-related diseases. Diagnosis of FH is frequently either missed or made with a considerable delay. Prompt identification of the disease is pivotal in implementing early prevention measures. Safe and effective drugs have been approved for use in children and adolescents, with statins, with or without ezetimibe, representing first-line therapy. At times, however, these medications may not be sufficient to achieve the therapeutic target, particularly in homozygous FH patients. Lipoprotein apheresis, which has proved safe and efficient, is strongly suggested in such cases. New drugs still at the investigational stage may represent a promising and personalised therapy. Lowering cholesterol levels in childhood hampers the formation of arterial atherosclerotic plaques, thus reducing cardiovascular events later in life. Accordingly, early detection, diagnosis, and therapy in FH subjects are priority aims.

Metabolomics in Otorhinolaryngology.

Otorhinolaryngology (Ear, Nose and Throat-ENT) focuses on inflammatory, immunological, infectious, and neoplastic disorders of the head and neck and on their medical and surgical therapy. The fields of interest of this discipline are the ear, the nose and its paranasal sinuses, the oral cavity, the pharynx, the larynx, and the neck. Besides surgery, there are many other diagnostic aspects of ENT such as audiology and Vestibology, laryngology, phoniatrics, and rhinology. A new advanced technology, named metabolomics, is significantly impacting the field of ENT. All the "omics" sciences, such as genomics, transcriptomics, and proteomics, converge at the level of metabolomics, which is considered the integration of all "omics." Its application will change the way several of ENT disorders are diagnosed and treated. This review highlights the power of metabolomics, including its pitfalls and promise, and several of its most relevant applications in ENT to provide a basic understanding of the metabolites associated with these districts. In particular, the attention has been focused on different heterogeneous diseases, from head and neck cancer to allergic rhinitis, hearing loss, obstructive sleep apnea, noise trauma, sinusitis, and Meniere's disease. In conclusion, metabolomics study indicates a "fil rouge" that links these pathologies to improve three aspects of patient care: diagnostics, prognostics, and therapeutics, which in one word is defined as precision medicine.

Twelve Months with COVID-19: What Gastroenterologists Need to Know.

Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal-oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care.

Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases.

BACKGROUND: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. METHODS: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. RESULTS: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. CONCLUSIONS: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research.

Pulmonary hypertension in pediatrics. A feasible approach to bridge the gap between real world and guidelines.

Pulmonary hypertension (PH) is quite infrequent in pediatric age and its most common etiologies include idiopathic pulmonary arterial hypertension, PH related to congenital heart diseases, bronchopulmonary dysplasia (chronic lung disease), persistence of pulmonary hypertension of the newborn, and congenital diaphragmatic hernia. The developed for adult patients PH classification shows limitations when applied to pediatric subjects since the underlying causes are markedly different between the two ages. In 2011, the Pulmonary Vascular Research Institute Panama Task Force outlined the first specific pediatric pulmonary hypertensive vascular disease diagnostic classification, including 10 main categories and 109 subcategories, thus testifying PH complex pathophysiology during newborns/children growth and development. The unique, distinctive features of pediatric PH were recognized also during the fifth World Symposium on pulmonary hypertension in 2013 and then confirmed in the recent 2018 sixth World Symposium. For the sake of uniformity, an attempt to adapt the adult classification to pediatric patients was made. However, all these commendable classifications are very complex and maybe not of quick comprehension for clinicians. A clinical simpler and simplified method is now suggested, comprising only five groups: neonatal, cardiac, developmental, idiopathic, and syndromic PH. This approach is not aimed at replacing the already existing classifications but is mainly based on the kind of specialized physician (neonatologist, pediatric cardiologist, pediatrician, pulmonologist, general practitioner) who first faces and looks after the child with suspected PH. What is dramatically known is that pediatric PH is a severe disease which, when untreated or undertreated, may lead to increased morbidity and mortality.

How could metabolomics change pediatric health?

In the last years, 'omics' technologies, and especially metabolomics, emerged as expanding scientific disciplines and promising technologies in the characterization of several pathophysiological processes.In detail, metabolomics, able to detect in a dynamic way the whole set of molecules of low molecular weight in cells, tissues, organs, and biological fluids, can provide a detailed phenotypic portray, representing a metabolic "snapshot."Thanks to its numerous strength points, metabolomics could become a fundamental tool in human health, allowing the exact evaluation of individual metabolic responses to pathophysiological stimuli including drugs, environmental changes, lifestyle, a great number of diseases and other epigenetics factors.Moreover, if current metabolomics data will be confirmed on larger samples, such technology could become useful in the early diagnosis of diseases, maybe even before the clinical onset, allowing a clinical monitoring of disease progression and helping in performing the best therapeutic approach, potentially predicting the therapy response and avoiding overtreatments. Moreover, the application of metabolomics in nutrition could provide significant information on the best nutrition regimen, optimal infantile growth and even in the characterization and improvement of commercial products' composition.These are only some of the fields in which metabolomics was applied, in the perspective of a precision-based, personalized care of human health.In this review, we discuss the available literature on such topic and provide some evidence regarding clinical application of metabolomics in heart diseases, auditory disturbance, nephrouropathies, adult and pediatric cancer, obstetrics, perinatal conditions like asphyxia, neonatal nutrition, neonatal sepsis and even some neuropsychiatric disorders, including autism.Our research group has been interested in metabolomics since several years, performing a wide spectrum of experimental and clinical studies, including the first metabolomics analysis of human breast milk. In the future, it is reasonable to predict that the current knowledge could be applied in daily clinical practice, and that sensible metabolomics biomarkers could be easily detected through cheap and accurate sticks, evaluating biofluids at the patient's bed, improving diagnosis, management and prognosis of sick patients and allowing a personalized medicine. A dream? May be I am a dreamer, but I am not the only one.

Metabolomics in pharmacology - a delve into the novel field of pharmacometabolomics.

Introduction: Pharmacometabolomics is an emerging science pursuing the application of precision medicine. Combining both genetic and environmental factors, the so-called pharmacometabolomic approach guides patient selection and stratification in clinical trials and optimizes personalized drug dosage, improving efficacy and safety.Areas covered: This review illustrates the progressive introduction of pharmacometabolomics as an innovative solution for enhancing the discovery of novel drugs and improving research and development (R&D) productivity of the pharmaceutical industry. An extended analysis on published pharmacometabolomics studies both in animal models and humans includes results obtained in several areas such as hepatology, gastroenterology, nephrology, neuropsychiatry, oncology, drug addiction, embryonic cells, neonatology, and microbiomics.Expert opinion: a tailored, individualized therapy based on the optimization of pharmacokinetics and pharmacodynamics, the improvement of drug efficacy, and the abolition of drug toxicity and adverse drug reactions is a key issue in precision medicine. Genetics alone has become insufficient for deciphring intra- and inter-individual variations in drug-response, since they originate both from genetic and environmental factors, including human microbiota composition. The association between pharmacogenomics and pharmacometabolomics may be considered the new strategy for an in-deep knowledge on changes and alterations in human and microbial metabolic pathways due to the action of a drug.

A review of current knowledge on Pollution, Cigarette Smoking and COVID-19 diffusion and their relationship with inflammation.

Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronavirus, Sars-Cov-2. This infection can cause mild to very severe respiratory and systemic illness mainly related with a cytokine storm. The epidemiology of COVID-19 is under continuous evolution, and studies are ongoing aiming at identifying the possible factors facilitating the diffusion of this infection. It is documented that air pollution and smoking are a leading cause of human morbidity and mortality globally, and can increase the risk of many diseases, including respiratory diseases. Overall, a linear relationship between exposure to atmospheric pollutants and diffusion of the Sars-Cov2 virus seems to exist. However, this correlation, cannot be regarded as a cause-effect relationship.  The available data show that air pollution is responsible for inflammation and hyper-activation of innate immunity that are associated with the worst outcomes of covid-19 but do not allow to conclude that atmospheric particulate is responsible for increased contagion. As to smoking, nicotine activation of nicotinic receptors leads to enhanced protease activation, apoptosis and inflammatory signaling through the same pathways (Renin-angiotensin system (RAS) and angiotensin-converting enzyme 2 (ACE2)) used by the virus increasing the inflammatory/destructive action of the virus itself. The increase in non-communicable diseases and of chronic inflammatory diseases is in line with environmental pollution, related climate changes, and with an augmented susceptibility to infectious diseases with increased contagiousness and morbidity. Restrictive measures to limit environmental pollution are needed worldwide as this represents a threat for human health.

Neonatal Congenital Central Hypoventilation Syndrome: Why We Should not Sleep on it. Literature Review of Forty-two Neonatal Onset Cases.

Congenital Central Hypoventilation Syndrome (CCHS), also referred with the expression "Ondine's Curse", is a rare genetic life-long disease resulting from the mutation of PHOX2B gene on chromosome 4p12.3. CCHS represents an autonomic nervous system disorder; its more fearsome manifestation is central hypoventilation, due to a deficient response of chemoreceptors to hypercapnia and hypoxia. Several associated symptoms can occur, such as pupillary anomalies, arrhythmias, reduced heart rate variability, esophageal dysmotility, and structural comorbidities (Hirschsprung's Disease or neural crest tumours). CCHS typical onset is during the neonatal period, but cases of delayed diagnosis have been reported; moreover, both sporadic or familial cases can occur. In preterm newborns, asphyxia and typical prematurity-related findings may overlap CCHS clinical manifestations and make it harder to formulate a correct diagnosis. The early recognition of CCHS allows appropriate management, useful to reduce immediate and long- term consequences.

The choice of amniotic fluid in metabolomics for the monitoring of fetus health - update.

Introduction: In recent years, several studies have highlighted the promising role of metabolomics in the analysis of amniotic fluid (AF), to describe and characterize the interactions occurring between the mother and the fetus during prenatal development. Among the available biological fluids, AF represents an ideal substrate to provide dynamic information regarding fetal organogenesis and metabolism through pregnancy, since it originates from both maternal and fetal tissues and contains substances derived from placenta, fetal skin, lungs, gastric fluid, and fetal urine. Areas covered: In this paper, we provide an update reporting the most recent results on AF metabolomics in the assessment of feto-maternal health, regarding physiological pregnancies but even fields such as prematurity, bronchopulmonary dysplasia, fetal malformations, chromosomopathies, maternal diseases, placental inflammation or infections, maternal diet or exposure to exogenous substances, according to the literature found on MEDLINE since 2015. Expert opinion: Metabolomics shows a promising role in describing both physiology and disease; the goal would be the identification of biomarkers able to precociously and efficaciously detect pathological conditions, allowing the identification of complicated pregnancy and improving their management. However, this field is under development and its reliability still needs to be clarified, especially through more numerous and accurate studies.

Oxidative Stress and Bronchopulmonary Dysplasia: Evidences From Microbiomics, Metabolomics, and Proteomics.

Bronchopulmonary dysplasia is a major issue affecting morbidity and mortality of surviving premature babies. Preterm newborns are particularly susceptible to oxidative stress and infants with bronchopulmonary dysplasia have a typical oxidation pattern in the early stages of this disease, suggesting the important role of oxidative stress in its pathogenesis. Bronchopulmonary dysplasia is a complex disease where knowledge advances as new investigative tools become available. The explosion of the "omics" disciplines has recently affected BPD research. This review focuses on the new evidence coming from microbiomics, metabolomics and proteomics in relation to oxidative stress and pathogenesis of bronchopulmonary dysplasia. Since the pathogenesis is not yet completely understood, information gained in this regard would be important for planning an efficacious prevention and treatment strategy for the future.

A gas chromatography-mass spectrometry (GC-MS) metabolomic approach in human colorectal cancer (CRC): the emerging role of monosaccharides and amino acids.

BACKGROUND: Colorectal cancer (CRC) has been confirmed to be the third most commonly diagnosed cancer in males and the second in females. We investigated the blood plasma metabolome in CRC patients and in healthy adults to elucidate the role of monosaccharides, amino acids, and their respective metabolic pathways as prognostic factors in patients with CRC. METHODS: Fifteen patients with CRC and nine healthy adults were enrolled in the study and their blood plasma samples analyzed by gas chromatography-mass spectrometry (GC-MS). Univariate Student's t-test, multivariate principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) were conducted on MetaboAnalyst 4.0. The analysis of metabolic profiles was carried out by the web-based extension Metabolite Sets Enrichment Analysis (MSEA). RESULTS: Overall, 125 metabolites were identified in plasma samples by GC-MS. In CRC patient samples, nine metabolites, including D-mannose and fructose, were significantly more abundant than in controls; conversely, eleven amino derivatives were less abundant, including methionine, valine, lysine, and proline. Methionine was significantly less abundant in died patients compared with survivors. The most significantly altered metabolic pathways in CRC patients are those involving monosaccharides (primarily the catabolic pathway of fructose and D-mannose), and amino acids (primarily methionine, valine, leucine, and isoleucine). CONCLUSIONS: The abundance of D-mannose in CRC patient samples contributes to inhibiting the growth of cancer cells, while the abundance of fructose may be consistent either with low consumption of fructose by aerobic glycolysis within cancer cells or with a high bioavailability of fructose from diet. The reduction in methionine concentration may be related to increased activity of the threonine and methionine catabolic pathways, confirmed by high levels of α-hydroxybutyrate.

Exposure to tobacco smoke and low birth weight: from epidemiology to metabolomics.

INTRODUCTION: The exposure to tobacco smoke during pregnancy is one of the leading causes of perinatal adverse outcomes such as stillbirth, intrauterine growth restriction (IUGR), and low birth weight, but the underlying biological mechanisms are still unclear. The incidence of this phenomenon maybe largely underestimated since the evaluation is made mainly by self-assessment questionnaires rather than measuring nicotine metabolites (such as cotinine) in biological fluids. In this context metabolomics may be useful to assess the actual number of pregnant women and to highlight the pathophysiological mechanisms that lead to the abovementioned adverse outcomes. Areas covered: The aims of this review are to analyze the literature and the application of the omics sciences, such as genomics and metabolomics concerning the negative effects of smoking during pregnancy in order to give a comprehensive picture of all the study made so far and to point out the potential of metabolomics as an investigative, predictive, and diagnostic tool. Expert commentary: Metabolomics in recent years has proved an excellent tool to try to understand the problems in perinatal medicine. With the increase in the number of studies we are convinced that it can be a useful instrument of investigation in this field.