A review of the impact of xenobiotics from dietary sources on infant health: Early life exposures and the role of the microbiota

Xenobiotics are worldwide distributed and humans are unavoidably exposed to multiple chemical compounds during life, from preconception to adulthood. The human microbiota is mainly settled during early life and modulate host health and fitness. One of the main routes for chemical exposure is by intake of contaminated food and water. Thus, the interplay between diet-xenobiotics-microbiota during pregnancy and perinatal period may have relevant consequences for infant and adult health. Maternal exposure to metal(oid)s, persistent organic pollutants, and some food additives can modify the infant’s microbiota with unknown consequences for child or adult health. Toxicants’ exposure may also modulate the maternal transfer of microorganisms to the progeny during birth and breastfeeding; however, scarce information is available. The rapid increase in releasing novel chemicals to the environment, the exposure to chemical mixtures, the chronic/low dose scenario, and the delay in science-stakeholders action call for novel and groundbreaking approaches to improve a comprehensive risk assessment in sensitive population groups like pregnant women and neonates, with emphasis on microbiota as modulating factor and target-organ of xenobiotic’s toxicity.Collado M.C. and Calatayud Arroyo M acknowledge the support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC starting grant, n° 639226) and the Project from The Ramón Areces Foundation (ref. CIVP19A5918). García Barrera T., Callejón Leblic B. and Arias Borrego A. have been supported by the projects UHU-1256905 from the FEDER Andalusian operative program (Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain) and PGC 2018-096608-B-C21 from the Spanish Ministry of Economy and Competitiveness (MINECO)Peer reviewe

Mice brain metabolomics after the exposure to a "chemical cocktail" and selenium supplementation through the gut-brain axis

Several environmental pollutants have been shown to damage brain and affect gut microbiota. Limited evidence is available about the impact of "chemical cocktails" (CC) of xenobiotics on brain metabolome and their possible influence in the gut-brain crosstalk. To this end, BALB/c mice were exposed to heavy metals (As, Hg, Cd) and pharmaceuticals (diclofenac and flumequine) under regular rodent diet or supplemented with selenium (Se). Selenium, an antioxidant well-known for its antagonism against the neurotoxicity of several pollutants, modulated several brain metabolic impairments caused by CC (e.g., brain levels of the excitatory amino acid N-acetyl aspartic acid) by influencing mainly the metabolisms of purine, glycosylate and dicarboxylate, glutamate, glycerophospholipid, alanine and aspartate. Numerous associations were obtained between brain metabolites and gut microbes and they changed after Se-supplementation (e.g., Lactobacillus was positively associated with a brain ceramide, phosphoserine, phosphocholine, vitamin D3 derivative, fatty acids, malic acid, amino acids, and urea after the exposure, but not after Se-supplementation). Our results showed numerous evidences about the impact of CC on brain metabolome, the potential role of Se as an antagonist and their impact on the gut-brain axis. Further research is needed to understand the complex mechanism of action implied on CC-brain-microbiota interactions.This work was supported by the projects: PG2018–096608-B-C21 and PID2021-123073NB-C21 from the Spanish Ministry of Science and Innovation (MICIN). Generación del Conocimiento. MCI/AEI/ FEDER “Una manera de hacer Europa”, UHU-1256905 and UHU-202009 from the FEDER Andalusian Operative Program 2014–2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). The authors are grateful to FEDER (European Community) for financial support, Grant UNHU13–1E-1611. CPM thanks MICIN for a predoctoral grant (ref. PRE2019–091650). Funding for open access charge: Universidad de Huelva / CBUA. The authors would like to acknowledge the support from The Ramón Areces Foundation (ref. CIVP19A5918).Peer reviewe

Selenium, selenoproteins and selenometabolites in mother and baby at time of birth.

The deficiency of Se, an essential micronutrient, has been implicated in adverse pregnancy outcomes. Our study was designed to determine total serum Se, selenoproteins (extracellular glutathione peroxidase (GPx-3), selenoprotein P (SeP)), selenoalbumin (SeAlb) and selenometabolites in healthy women and their newborns at delivery. This cross-sectional study included eighty-three healthy mother–baby couples. Total Se and Se species concentrations were measured in maternal and umbilical cord sera by an in-series coupling of two-dimensional size-exclusion and affinity HPLC. Additional measurements of serum SeP concentration and of serum GPx-3 enzyme activity were carried out using ELISA. Total Se concentration was significantly higher in maternal serum than in cord serum (68·9 (sd 15·2) and 56·1 (sd 14·6) µg/l, respectively; P<0·01). There were significant correlations between selenoprotein and SeAlb concentrations in mothers and newborns, although they also showed significant differences in GPx-3 (11·2 (sd 3·7) v. 10·5 (sd 3·5) µg/l; P<0·01), SeP (42·5 (sd 9·5) v. 28·1 (sd 7·7) µg/l; P<0·01) and SeAlb (11·6 (sd 3·6) v. 14·1 (sd 4·3) µg/l; P<0·01) concentrations in maternal and cord sera, respectively. Serum GPx-3 activity and concentration were positively correlated in mothers (r 0·33; P=0·038) but not in newborns. GPx-3 activity in cord serum was significantly correlated with gestational age (r 0·44; P=0·009). SeAlb concentration was significantly higher in babies, whereas SeP and GPx-3 concentrations were significantly higher in mothers. The differences cannot be explained by simple diffusion; specific transfer mechanisms are probably involved. GPx-3 concentrations in mothers, at delivery, are related to maternal Se status, whereas the GPx-3 activity in cord serum depends on gestational age

Selenium, selenoproteins and selenometabolites in mother and baby at time of birth.

The deficiency of Se, an essential micronutrient, has been implicated in adverse pregnancy outcomes. Our study was designed to determine total serum Se, selenoproteins (extracellular glutathione peroxidase (GPx-3), selenoprotein P (SeP)), selenoalbumin (SeAlb) and selenometabolites in healthy women and their newborns at delivery. This cross-sectional study included eighty-three healthy mother–baby couples. Total Se and Se species concentrations were measured in maternal and umbilical cord sera by an in-series coupling of two-dimensional size-exclusion and affinity HPLC. Additional measurements of serum SeP concentration and of serum GPx-3 enzyme activity were carried out using ELISA. Total Se concentration was significantly higher in maternal serum than in cord serum (68·9 (sd 15·2) and 56·1 (sd 14·6) µg/l, respectively; P<0·01). There were significant correlations between selenoprotein and SeAlb concentrations in mothers and newborns, although they also showed significant differences in GPx-3 (11·2 (sd 3·7) v. 10·5 (sd 3·5) µg/l; P<0·01), SeP (42·5 (sd 9·5) v. 28·1 (sd 7·7) µg/l; P<0·01) and SeAlb (11·6 (sd 3·6) v. 14·1 (sd 4·3) µg/l; P<0·01) concentrations in maternal and cord sera, respectively. Serum GPx-3 activity and concentration were positively correlated in mothers (r 0·33; P=0·038) but not in newborns. GPx-3 activity in cord serum was significantly correlated with gestational age (r 0·44; P=0·009). SeAlb concentration was significantly higher in babies, whereas SeP and GPx-3 concentrations were significantly higher in mothers. The differences cannot be explained by simple diffusion; specific transfer mechanisms are probably involved. GPx-3 concentrations in mothers, at delivery, are related to maternal Se status, whereas the GPx-3 activity in cord serum depends on gestational age

Different metals can be early biomarkers for lung cancer

Fundamento y objetivos: el cáncer de pulmón (CP) es el que provoca mayor mortalidad, especialmente por su frecuente diagnóstico tardío, con menos posibilidades de curación. En el inicio del proceso carcinogénico, previo al diagnóstico clínico, los oligoelementos (metales o metaloides), desempeñan un papel importante al activar o inhibir las reacciones enzimáticas y las metaloproteínas. El objetivo de nuestro estudio es analizar la utilidad de diversos metales como biomarcadores (BM) precoces de CP, obtenidos en muestras de suero, orina, y lavado broncoalveolar (LBA) Material y métodos: hemos analizado las concentraciones totales, incluyendo fracciones de alto y bajo peso molecular, de 11 metales en muestras de suero, orina y LBA de pacientes CP, controles sanos (CS) y pacientes con patología respiratoria no cáncer (NCP) empleando una técnica de análisis basada en un plasma de acoplamiento inductivo-espectrometría de masas (ICP-QQQ-MS) Resultados: obtuvimos una clara discriminación entre los grupos en las tres muestras analizadas. Hemos obtenido metales sobreexpresados o reducidos en el CP que podrían utilizarse como BM. La concentración de vanadio (V) y cromo (Cr) en suero es claramente mayor en pacientes con CP. Hemos demostrado que varios metales (V, Cr y cobre), relacionados con procesos metabólicos alterados en CP como estrés oxidativo y homeostasis, y/o sus relaciones podrían ser buenos BM de CP. Conclusiones: diversos metales, y sus relaciones y correlaciones, en la población estudiada diferencian claramente a los pacientes con cáncer de pulmón de los CS y NCP y parecen ser buenos biomarcadores en el diagnóstico precoz del cáncer de pulmón.Background and objectives: Lung cancer (LC) has the highest mortality rate, especially due to its late diagnosis, with a lower chance of recovery. At the start of the carcinogenic process, before a clinical diagnosis, trace elements (metals or metalloids) play an important role by activating or inhibiting enzymatic reactions and metalloproteins. The objective of our study is to analyze the utility of different metals as early biomarkers (BM) for LC which are obtained in serum, urine and bronchoalveolar lavage (BAL) samples. Material and methods: We analyzed the total concentrations, including fractions of high and low molecular weight, of 11 metals in serum, urine and BAL samples from patients with LC, healthy controls (HC) and patients with non-cancerous respiratory pathology (NCP) using an analysis technique based on inductively coupled plasma mass spectrometry (ICP-QQQ-MS). Results: We obtained a clear discrimination between groups for the three samples analyzed. We obtained overexpressed or reduced metals in LC that could be used as BM. The concentration of vanadium (V) and chromium (Cr) in serum is clearly higher in patients with LC. We have shown that several metals (V, Cr and copper) related to the altered metabolic processes in LC such as oxidative stress and homeostasis and/ or their connections could be good BM for LC. Conclusions: in the population studied, several metals and their connections and correlations were clearly differentiated in the patients with lung cancer compared to the HC and NCP groups and they appear to be good biomarkers for the early diagnosis of lung cancer

Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent

Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3–6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3′-dione were found altered in PRE, and their levels returned to those of a baseline control group 3–6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods