Metabolomics and fetal-neonatal nutrition: Between "not enough" and "too much"

Metabolomics is a new analytical technique defined as the study of the complex system of metabolites that is capable of describing the biochemical phenotype of a biological system. In recent years the literature has shown an increasing interest in paediatric obesity and the onset of diabetes and the metabolic syndrome in adulthood. Some studies show that fetal malnutrition, both excessive and insufficient, may permanently alter the metabolic processes of the fetus and increase the risk of future chronic pathologies. At present then, attention is being focused mainly on the formulation of new hypotheses, by means of metabolomics, concerning the biological mechanisms to departure from fetal-neonatal life that may predispose to the development of these diseases. © 1996-2013 MDPI AG

Integrative Multiomics Approach to Skin: The Sinergy between Individualised Medicine and Futuristic Precision Skin Care?

The skin is a complex ecosystem colonized by millions of microorganisms, the skin microbiota, which are crucial in regulating not only the physiological functions of the skin but also the metabolic changes underlying the onset of skin diseases. The high microbial colonization together with a low diversity at the phylum level and a high diversity at the species level of the skin is very similar to that of the gastrointestinal tract. Moreover, there is an important communication pathway along the gut-brain-skin axis, especially associated with the modulation of neurotransmitters by the microbiota. Therefore, it is evident that the high complexity of the skin system, due not only to the genetics of the host but also to the interaction of the host with resident microbes and between microbe and microbe, requires a multi-omics approach to be deeply understood. Therefore, an integrated analysis, with high-throughput technologies, of the consequences of microbial interaction with the host through the study of gene expression (genomics and metagenomics), transcription (transcriptomics and meta-transcriptomics), and protein production (proteomics and meta-proteomics) and metabolite formation (metabolomics and lipidomics) would be useful. Although to date very few studies have integrated skin metabolomics data with at least one other 'omics' technology, in the future, this approach will be able to provide simple and fast tests that can be routinely applied in both clinical and cosmetic settings for the identification of numerous skin diseases and conditions. It will also be possible to create large archives of multi-omics data that can predict individual responses to pharmacological treatments and the efficacy of different cosmetic products on individual subjects by means of specific allotypes, with a view to increasingly tailor-made medicine. In this review, after analyzing the complexity of the skin ecosystem, we have highlighted the usefulness of this emerging integrated omics approach for the analysis of skin problems, starting with one of the latest 'omics' sciences, metabolomics, which can photograph the expression of the genome during its interaction with the environment

Metabolomic profiles and microbiota of GDM offspring: The key for future perspective?

Gestational diabetes mellitus (GDM), or any degree of glucose intolerance recognized for the first time during pregnancy, is one of the diseases that most frequently aggravates the course of gestation. Missed or late diagnosis and inadequate treatment are associated with high maternal and fetal morbidity, with possible short- and long-term repercussions. Estimates on the prevalence of GDM are alarming and increasing by about 30% in the last 10-20 years. In addition, there is the negative influence of the SARS-CoV-2 emergency on the glycemic control of pregnant women, making the matter increasingly topical. To date, knowledge on the metabolic maturation of newborns is still incomplete. However, in light of the considerable progress of the theory of "developmental origins of health and disease," the relevant role of the intrauterine environment cannot be overlooked. In fact, due to the high plasticity of the early stages of development, some detrimental metabolic alterations during fetal growth, including maternal hyperglycemia, are associated with a higher incidence of chronic diseases in adult life. In this context, metabolomic analysis which allows to obtain a detailed phenotypic portrait through the dynamic detection of all metabolites in cells, tissues and different biological fluids could be very useful for the early diagnosis and prevention of complications. Indeed, if the diagnostic timing is optimized through the identification of specific metabolites, the detailed understanding of the altered metabolic pathway could also allow better management and more careful monitoring, also from a nutritional profile, of the more fragile children. In this context, a further contribution derives from the analysis of the intestinal microbiota, the main responsible for the fecal metabolome, given its alteration in pregnancies complicated by GDM and the possibility of transmission to offspring. The purpose of this review is to analyze the available data regarding the alterations in the metabolomic profile and microbiota of the offspring of mothers with GDM in order to highlight future prospects for reducing GDM-related complications in children of mothers affected by this disorder

Clinical metabolomics and nutrition: the new frontier in neonatology and pediatrics.

In the pediatric clinic, nutritional research is focusing more and more on preventing the development of long-term diseases as well as supporting the repair processes important in the therapy of already fully developed diseases. Most children who are hospitalized or affected by chronic diseases could benefit from specific and careful attention to nutrition. Indeed, the state of nutrition modulates all body functions, including the different metabolic processes which, all together, have a profound effect on the development of the health and future of all individuals. Inappropriate food, even in the first periods of life, can accelerate the development of chronic metabolic diseases, especially in the pediatric age. To gain further insights into metabolic cycles and how they are connected with diet and health, nutrition and metabolomics interact to develop and apply modern technologies for metabolic assessment. In particular, nutritionists are evaluating the metabolomic approach to establish the single nutritional phenotypes, that is, the way in which diet interacts with individuals' metabolisms. This strategy offers the possibility of providing a complete definition of the individual's nutritional and health status, predict the risk of disease, and create metabolomic databases supporting the development of "personalized nutrition," in which diet is attuned to the nutritional needs of individual patients

Metabolomics in Children Cow’s Milk Protein Allergy: Possible Contribution from a System Biology Approach?

One of the most frequent triggers of food anaphylaxis in pediatric age but also among the most common, early, and complex causes of childhood food allergy is cow's milk protein allergy (CMPA). The diagnostic course and management of this allergy is defined in a complex clinical picture due to several factors. First of all, the epidemiological data are not uniform, mainly as a consequence of the diagnostic methodology used in the various studies and the different age ranges covered. In addition, there is the complexity of terminology, since although CMPA traditionally refers to immune-mediated reactions to cow's milk, it is a term encompassing numerous clinical features with different symptoms and the requirement for specific treatments. Moreover, the differential diagnosis with other very frequent diseases, especially in the first year of life, such as gastro-esophageal reflux disease or colic, is still complex. This can result in misdiagnosis and incorrect treatment, with harmful health consequences and significant economic repercussions. In this context, the combination of several omics sciences together, which have already proved useful in clarifying the allergenicity of cow's milk proteins with greater precision, could improve the diagnostic tests currently in use through the identification of new, more specific, and precise biomarkers that make it possible to improve diagnostic accuracy and predict the patient's response to the various available treatments for the recovery of tolerance

Childhood Obesity and the Cryptic Language of the Microbiota: Metabolomics' Upgrading

The growing obesity epidemic in childhood is increasingly concerning for the related physical and psychological consequences, with a significant impact on health care costs in both the short and the long term. Nonetheless, the scientific community has not yet completely clarified the complex metabolic mechanisms underlying body weight alterations. In only a small percentage of cases, obesity is the result of endocrine, monogenic, or syndromic causes, while in much more cases, lifestyle plays a crucial role in obesity development. In this context, the pediatric age appears to be of considerable importance as prevention strategies together with early intervention can represent important therapeutic tools not only to counteract the comorbidities that increasingly affect children but also to hinder the persistence of obesity in adulthood. Although evidence in the literature supporting the alteration of the microbiota as a critical factor in the etiology of obesity is abundant, it is not yet fully defined and understood. However, increasingly clear evidence is emerging regarding the existence of differentiated metabolic profiles in obese children, with characteristic metabolites. The identification of specific pathology-related biomarkers and the elucidation of the altered metabolic pathways would therefore be desirable in order to clarify aspects that are still poorly understood, such as the consequences of the interaction between the host, the diet, and the microbiota. In fact, metabolomics can characterize the biological behavior of a specific individual in response to external stimuli, offering not only an eventual effective screening and prevention strategy but also the possibility of evaluating adherence and response to dietary intervention

Metabolomics in NEC: An Updated Review

Necrotizing enterocolitis (NEC) represents the most common and lethal acute gastrointestinal emergency of newborns, mainly affecting those born prematurely. It can lead to severe long-term sequelae and the mortality rate is approximately 25%. Furthermore, the diagnosis is difficult, especially in the early stages, due to multifactorial pathogenesis and complex clinical pictures with mild and non-specific symptoms. In addition, the existing tests have poor diagnostic value. Thus, the scientific community has been focusing its attention on the identification of non-invasive biomarkers capable of prediction, early diagnosis and discriminating NEC from other intestinal diseases in order to intervene early and block the progression of the pathology. In this regard, the use of "omics" technologies, especially metabolomics and microbiomics, could be a fundamental synergistic strategy to study the pathophysiology of NEC. In addition, a deeper knowledge of the microbiota-host cross-talk can clarify the metabolic pathways potentially involved in the pathology, allowing for the identification of specific biomarkers. In this article, the authors analyze the state-of-the-art concerning the application of metabolomics and microbiota analysis to investigate this pathology and discuss the future possibility of the metabolomic fingerprint of patients for diagnostic purposes

Metabolomics in Pediatric Neuropsychiatry

Metabolomics is one of the newest “omics” sciences that is being applied to date to investigate several aspects of pathologies and medical topics in general. It provides a snapshot of the metabolic state of an individual by the detection of metabolites in several biological fluids, such as saliva, blood and sweat. Our research group has more than a decade of experience in this field and we ourselves applied this technology to investigate, for instance, every aspect of breast milk, different neonatal diseases and neuropsychiatric disorders. In this paper, which is adapted from the lecture given by Professor Fanos at the 5th edition of the Galatia Congress (2021), we discuss the usefulness of metabolomics in the investigation of paediatric neuropsychiatric disorders. We are convinced that this technique, in the future, will provide all the answer to the infinite questions concerning the paediatric brain and its disorders, in order to help the clinicians and families of these children to give the best life possible to these little patients.</em

Breast milk stem cells: four questions looking for an answer

The finding of stem/progenitor cells in the maternal milk and the discovery of their multilineage potential, associated with some evidence regarding the ability of maternal cells to cross the gastrointestinal barrier and integrate into the organs of the breastfed neonate, has opened an intriguing debate, regarding the strict relationship between mother and son in the postnatal period. In particular, thanks to the discovery of the presence in high quantities of mammary stem cells, a new vision of maternal milk is emerging, in which breastfeeding appears as an unique occasion for reinforcing the physiological development of the newborn, putting all the formulas at a different level of relevance for the neonate. In this contribution the authors try to give an answer to the following 4 questions: 1. is there heterogeneity and a hierarchy among breast milk stem cells? 2. can stem cells present in breast milk enter into the newborn organism? 3. can breast milk stem cells integrate in the neonatal organs and differentiate toward different tissues, including neurons and neuroglia? 4. could metabolomics be useful for the study of stem cells in the human milk

Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life.

BACKGROUND: Perinatal asphyxia is a severe clinical condition affecting around four million newborns worldwide. It consists of an impaired gas exchange leading to three biochemical components: hypoxemia, hypercapnia and metabolic acidosis. METHODS: The aim of this longitudinal experimental study was to identify the urine metabolome of newborns with perinatal asphyxia and to follow changes in urine metabolic profile over time. Twelve babies with perinatal asphyxia were included in this study; three babies died on the eighth day of life. Total-body cooling for 72 hours was carried out in all the newborns. Urine samples were collected in each baby at birth, after 48 hours during hypothermia, after the end of the therapeutic treatment (72 hours), after 1 week of life, and finally after 1 month of life. Urine metabolome at birth was considered the reference against which to compare metabolic profiles in subsequent samples. Quantitative metabolic profiling in urine samples was measured by gas chromatography mass spectrometry (GC-MS). The statistical approach was conducted by using the multivariate analysis by means of principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). Pathway analysis was also performed. RESULTS: The most important metabolites depicting each time collection point were identified and compared each other. At birth before starting therapeutic hypothermia (TH), urine metabolic profiles of the three babies died after 7 days of life were closely comparable each other and significantly different from those in survivors. CONCLUSIONS: In conclusion, a plethora of data have been extracted by comparing the urine metabolome at birth with those observed at each time point collection. The modifications over time in metabolites composition and concentration, mainly originated from the depletion of cellular energy and homeostasis, seems to constitute a fingerprint of perinatal asphyxia