The role of selenium in shaping mice brain metabolome and selenoproteome through the gut-brain axis by combining metabolomics, metallomics, gene expression, and amplicon sequencing.

Selenium (Se) is a trace element crucial for human health. Recently, the impact of Se supplementation on gut microbiota has been pointed out as well as its influence on the expression of certain selenoproteins and gut metabolites. This study aims to elucidate the link between Se supplementation, brain selenoproteins and brain metabolome as well as the possible connection with the gut-brain axis. To this end, an in vivo study with 40 BALB/c mice was carried out. The study included conventional (n=20) and mice model with microbiota depleted by antibiotics (n=20) under a regular or Se supplemented diet. Brain selenoproteome was determined by a transcriptomic/gene expression profile, while brain metabolome and gut microbiota profiles were accomplished by untargeted metabolomics and amplicon sequencing, respectively. The total content of Se in brain was also determined. The selenoproteins genes Dio and Gpx isoenzymes, SelenoH, SelenoI, SelenoT, SelenoV, and SelenoW and 31 metabolites were significantly altered in the brain after Se supplementation in conventional mice, while 11 selenoproteins and 26 metabolites were altered in microbiota depleted mice. The main altered brain metabolites were related to glyoxylate and dicarboxylate metabolism, amino acid metabolism, and gut microbiota that have been previously related with the gut-brain axis (e.g., members of Lachnospiraceae and Ruminococcaceae families). Moreover, specific associations were determined between brain selenoproteome and metabolome, which correlated with the same bacteria, suggesting an intertwined mechanism. Our results demonstrated the effect of Se on brain metabolome through specific selenoproteins gene expression and gut microbiota.

Single and joint effects of cadmium and selenium on bioaccumulation, oxidative stress and metabolomic responses in the clam Scrobicularia plana.

Selenium (Se) is a vital trace element for many living organisms inclusive of aquatic species. Although the antagonistic action of this element against other pollutants has been previously described for mammals and birds, limited information on the join effects in bivalves is available. To this end, bivalves of the species Scrobicularia plana were exposed to Se and Cd individually and jointly. Digestive glands were analysed to determine dose-dependent effects, the potential influence of Se on Cd bioaccumulationas well as the possible recover of the oxidative stress and metabolic alterations induced by Cd. Selenium co-exposure decreased the accumulation of Cd at low concentrations. Cd exposure significantly altered the metabolome of clams such as aminoacyltRNA biosynthesis, glycerophospholipid and amino acid metabolism, while Se co-exposure ameliorated several altered metabolites such asLysoPC (14:0), LysoPE (20:4), LysoPE (22:6), PE (14:0/18:0), PE (20:3/18:4) andpropionyl-l-carnitine.Additionally, Se seems to be able to regulate the redox status of the digestive gland of clams preventing the induction of oxidativedamage in this organ. This study shows the potential Se antagonism against Cd toxicity in S. plana and the importance to study join effects of pollutants to understand the mechanism underlined the effects.

Selenium supplementation influences mice testicular selenoproteins driven by gut microbiota.

Selenium is a well-known essential element with important roles in human reproductive health mainly due to its antioxidant character. This study aimed to investigate the potential role of selenoproteins on gut microbiota and male reproductive health. A new assay for the absolute quantification of selenoproteins in testicular tissue based on two dimensional chromatography with inductively coupled plasma mass spectrometry was performed for the first time. The gut microbiota profile was obtained by 16S rRNA gene sequencing. Numerous associations were found between testicular selenoproteins and gut microbiota (e.g. Mucispirillum, related with sperm activity and testosterone, was associated with glutathione peroxidase (GPx) and selenoalbumin (SeAlb), while Escherichia/Shigella, related to sex hormones, correlated with GPx, selenoprotein P (SelP) and SeAlb). The effects of Se-supplementation on testicular selenoproteins only occur in conventional mice, suggesting a potential selenoproteins-microbiota interplay that underlies testicular function. The selenoproteins GPx and SelP have been quantified for the first time in the testicles, and the novel identification of SeAlb, a protein with nonspecifically incorporated Se, is also reported. These findings demonstrate the significant impact of Se-supplementation on gut microbiota and male reproductive health. In addition, the analytical methodology applied here in selenoprotein quantification in testicular tissue opens new possibilities to evaluate their role in gut microbiota and reproductive health axis.

Omic methodologies for assessing metal(-loid)s-host-microbiota interplay: A review.

Omic methodologies have become key analytical tools in a wide number of research topics such as systems biology, environmental analysis, biomedicine or food analysis. They are especially useful when they are combined providing a new perspective and a holistic view of the analytical problem. Methodologies for microbiota analysis have been mostly focused on genome sequencing. However, information provided by these metagenomic studies is limited to the identification of the presence of genes, taxa and their inferred functionality. To achieve a deeper knowledge of microbial functionality in health and disease, especially in dysbiosis conditions related to metal and metalloid exposure, the introduction of additional meta-omic approaches including metabolomics, metallomics, metatranscriptomics and metaproteomics results essential. The possible impact of metals and metalloids on the gut microbiota and their effects on gut-brain axis (GBA) only begin to be figured out. To this end new analytical workflows combining powerful tools are claimed such as high resolution mass spectrometry and heteroatom-tagged proteomics for the absolute quantification of metal-containing biomolecules using the metal as a "tag" in a sensitive and selective detector (e.g. ICP-MS). This review focus on current analytical methodologies related with the analytical techniques and procedures available for metallomics and microbiota analysis with a special attention on their advantages and drawbacks.

Environmental metal toxicity assessment by the combined application of metallomics and metabolomics.

The growing interest of our society for the environment, climate change, and the assurance of the quality of life and health has been the motor of new methodological proposals that allow a more comprehensive knowledge of the problems to be solved. In this sense, the potential of omic methodologies to study these problems from a global perspective represents a milestone in environmental studies. Therefore, the study of essential and toxic metals has a special interest, particularly in relation to toxicity issues and their association to biological interactions, transport, binding to biomolecules, and behavior in biological interfaces. These studies have promoted new instrumental platforms and methodological approaches that allow addressing these problems. Furthermore, to encompass the reality of molecule-atoms interactions in their completeness, combinations of omics have been tried, focusing on environment, food, and health issues. In this sense, the present work is situated, with the objective of reviewing the most recent methodological proposals in the field of the environment and their applications, considering not only the analytical approaches but also how they have to be applied, the use of bioindicators' exposure experiments in the laboratory, and the potential transfer of the findings from the laboratory to the field. This latter point is a true touchstone, which makes these new analytical methodologies in the necessary tools for understanding the environment and the consequences of its imbalance.

Arsenic, cadmium, and selenium exposures and bone mineral density-related endpoints: The HORTEGA study.

BACKGROUND AND OBJECTIVES: Experimental data suggest that trace elements, such as arsenic (As), cadmium (Cd), and selenium (Se) can influence the bone remodeling process. We evaluated the cross-sectional association between As, Cd, and Se biomarkers with bone mineral density (BMD) measured at the calcaneus, in a representative sample of a general population from Spain. As secondary analyses we evaluated the associations of interest in subgroups defined by well-established BMD determinants, and also conducted prospective analysis of osteoporosis-related incident bone fractures restricted to participants older than 50 years-old. METHODS: In N = 1365 Hortega Study participants >20 years-old, urine As and Cd were measured by inductively coupled-plasma mass spectrometry (ICPMS); plasma Se was measured by atomic absorption spectrometry (AAS) with graphite furnace; and BMD at the calcaneus was measured using the Peripheral Instaneuous X-ray Imaging system (PIXI). As levels were corrected for arsenobetaine (Asb) to account for inorganic As exposure. RESULTS: The median of total urine As, Asb-corrected urine As, urine Cd, and plasma Se was 61.3, 6.53 and 0.39 µg/g creatinine, and 84.9 µg/L, respectively. In cross-sectional analysis, urine As and Cd were not associated with reduced BMD (T-score < -1 SD). We observed a non-linear dose-response of Se and reduced BMD, showing an inverse association below ~105 µg/L, which became increasingly positive above ~105 µg/L. The evaluated subgroups did not show differential associations. In prospective analysis, while we also observed a U-shape dose-response of Se with the incidence of osteoporosis-related bone fractures, the positive association above ~105 µg/L was markedly stronger, compared to the cross-sectional analysis. CONCLUSIONS: Our results support that Se, but not As and Cd, was associated to BMD-related disease. The association of Se and BMD-related disease was non-linear, including a strong positive association with osteoporosis-related bone fractures risk at the higher Se exposure range. Considering the substantial burden of bone loss in elderly populations, additional large prospective studies are needed to confirm the relevance of our findings to bone loss prevention in the population depending on Se exposure levels.

Metabolic Impairments Caused by a "Chemical Cocktail" of DDE and Selenium in Mice Using Direct Infusion Triple Quadrupole Time-of-Flight and Gas Chromatography-Mass Spectrometry.

Among organic contaminants, pesticides are one of the most important groups of chemicals due to their persistent character and toxicity. However, the biological systems are exposed to a complex environment in which the contaminants can interact in a synergistic/antagonistic fashion, and for this reason, the study of "chemical cocktails" is of great interest to fully understand the final biological effect. In this way, selenium is known for its antagonistic action against several toxicants. In this paper, metabolic impairments caused by the joint exposure of p,p'-dichloro diphenyl trichloroethane (DDE) and selenium (Se) have been issued for the first time. A metabolomic workflow was applied to mice fed DDE and DDE with Se diet, on the basis of the complementary use of two organic mass spectrometric techniques, combining direct infusion mass spectrometry (DI-ESI-QqQ-TOF MS) and gas chromatography-mass spectrometry (GC-MS). The results show a good classification between the studied groups caused by about 70 altered metabolites in the liver, kidney, or brain, including the pathways of energy metabolism, degradation of phospholipidic membrane, ß-oxidation, and oxidative stress, which confirm the potential of combined metabolomic platforms in environmental studies.

Metabolomic study of bioactive compounds in strawberries preserved under controlled atmosphere based on GC-MS and DI-ESI-QqQ-TOF-MS.

INTRODUCTION: The storage of the vegetables products in a controlled atmosphere (CA) with low O2 and high CO2 concentrations, reduces respiration rates and delays the ripening process, and in some cases, improves their quality and organoleptic properties. OBJECTIVE: To obtain deep insight into strawberry fruit metabolic changes caused by these CA treatments. METHODOLOGY: Freshly harvested strawberries were preserved under different atmospheres enriched with 10%, 20% and 30% of CO2 , for 2 days at 0°C, containing in all the cases 5% of O2 and were subjected to a metabolomic analysis based on gas chromatography-mass spectrometry (GC-MS) and direct-infusion with electrospray ionisation source equipped with triple quadrupole coupled to time of flight mass spectrometry (DI-ESI-QqQ-TOF-MS). Partial least square discriminant analysis (PLS-DA) was employed to compare the control and treated samples for the identification of altered metabolites. RESULTS: Several metabolites related to CA treatment could be identified by databases and literature, which are mainly sugars, organic acids and phenolic compounds (bioactive compounds). CONCLUSIONS: Good correlation coefficients were obtained between discriminant metabolites and fruit quality parameters. These results suggest that treated strawberries under CA could be considered as bioactive healthy compounds, suggesting that treated strawberries under CA could be used as raw material for the preparation and formulation of food supplements and nutraceutical products.

Environmental Metallomics.

Metallomics is the new paradigm about the metallobiomolecules related to living organisms, considering the interactions between toxic and essential metals, transport through biological fluids, passing across biological membranes and interfaces, synergic and antagonist actions among metal species, and alterations in metabolic pathways triggered by overexpression or inhibition of these metallobiomolecules. These challenging studies require the development of new analytical approaches in order to get suitable information of these species close to their native environment which has promoted the application of new tools based in mass spectrometry under the double focus of elemental (ICP-MS) and molecular (Qq-TOF-MS) mass spectrometry, generally arranged with chromatography in multidimensional platforms. The driving force for the design of these new analytical instrumental arrangements is the analyst imagination who adapts the new metallomic methodology to the new problems. In this work the most recent metallomic approaches proposed have been considered, deepening their application to the most frequent problems related to metal toxicity in environmental issues, such as exposure experiments of mice to toxic metals, interactions and homeostasis of metals, metal imaging, metabolic alterations caused by metallobiomolecules over- or down-expressed, and more interestingly real-life consequences of metal species expression in environmental field studies. In this way, the application of two-dimensional chromatographic approaches with ICP-MS detection, the use of multidimensional chromatography-column-switching-ICP-MS devices, metal imaging with LA-ICP-MS, combined application of metallomics and metabolomics for environmental toxicological appraisal, and the application of these metallomic techniques in environmental field studies have been reviewed.