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.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 . MCIN/ AEI /10.13039/50110 0 011033/ 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). S.R.A. thanks the Spanish Ministry of Science and Innovation for a PhD scholarship ( BES-2016-076364 ). The authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611 . The authors would like to acknowledge the support from The Ramón Areces Foundation (ref. CIVP19A5918 ). Funding for open access charge: Universidad de Huelva / CBUA

Proteomic profile of the effects of low-dose bisphenol A on zebrafish ovaries

Human exposure to bisphenol-A (BPA) is largely unavoidable because BPA is an environmental contaminant found in soil, water, food and indoor dust. The safety of authorized BPA amounts in consumer products is under question because new studies have reported adverse effects of BPA at doses far below that previously established by the NOAEL (50 μg/kg per day). To protect public health, the consequences of low-dose BPA exposure in different organs and organismal functions must be further studied to generate relevant data. This study attempted to investigate the effects and potential molecular mechanisms of short-term exposure to 1 μg/L BPA on zebrafish ovarian follicular development. We observed only minor changes at the histopathological level with a small (3 %) increase in follicular atresia. However, a shotgun proteomics approach indicated deep alterations in BPA-exposed ovarian cells, including induction of the oxidative stress response, metabolic shifts and degradome perturbations, which could drive oocytes towards premature maturation. Based on these results, it could be suggested that inadvertent exposure to small concentrations of BPA on a continuous basis causes alteration in biological processes that are essential for healthy reproduction

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.This work was supported by the projects PG2018-096608-B-C21 from the Spanish Ministry of Economy and Competitiveness (MINECO) and UHU-1256905 from the FEDER Andalusian Operative Program 2014–2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). S.R.A. thanks the Spanish Ministry of Science and Innovation for a PhD scholarship (BES-2016-076364). The authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611. The authors would like to acknowledge the support from The Ramón Areces Foundation (ref. CIVP19A5918).Peer reviewe