Endobolome, a New Concept for Determining the Influence of Microbiota Disrupting Chemicals (MDC) in Relation to Specific Endocrine Pathogenesis

This work was carried out within the frame of GP/EFSA/ENCO/380 2018/03/G04: OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers. This research was also funded by Spanish State Research Agency (SRA) EIN2019-103431, EIN2019-103082 and Proyecto cofinanciado FEDER-Consejeria de Salud y Familias, Junta de Andalucia PE-0250-2019.The results presented in this article constitute part of YG-O doctoral thesis, performed in the Nutrition and Food Sciences Doctorate Program of the University of Granada.Endogenous steroid hormones and Endocrine Disrupting Chemicals (EDC) interact with gut microbiota through different pathways. We suggest the use of the term “endobolome” when referring to the group of gut microbiota genes and pathways involved in the metabolism of steroid hormones and EDC. States of dysbiosis and reduced diversity of the gut microbiota may impact and modify the endobolome resulting at long-term in the development of certain pathophysiological conditions. The endobolome might play a central role in the gut microbiota as seen by the amount of potentially endobolome-mediated diseases and thereby it can be considered an useful diagnostic tool and therapeutic target for future functional research strategies that envisage the use of next generation of probiotics. In addition, we propose that EDC and other xenobiotics that alter the gut microbial composition and its metabolic capacities should be categorized into a subgroup termed “microbiota disrupting chemicals” (MDC). This will help to distinguish the role of contaminants from other microbiota natural modifiers such as those contained or released from diet, environment, physical activity and stress. These MDC might have the ability to promote specific changes in the microbiota that can ultimately result in common intestinal and chronic or long-term systemic diseases in the host. The risk of developing certain disorders associated with gut microbiota changes should be established by determining both the effects of the MDC on gut microbiota and the impact of microbiota changes on chemicals metabolism and host susceptibility. In any case, further animal controlled experiments, clinical trials and large epidemiological studies are required in order to establish the concatenated impact of the MDC-microbiota-host health axis.OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers GP/EFSA/ENCO/380 2018/03/G04Spanish State Research Agency (SRA) EIN2019-103431 EIN2019-103082Junta de Andalucia PE-0250-201

Endocrine Disruptors in Food: Impact on Gut Microbiota and Metabolic Diseases

The results presented in this article constitute part of Yolanda Gálvez-Ontiveros doctoral thesis, performed in the Nutrition and Food Sciences Doctorate Program of the University of Granada.Endocrine disruptors (EDCs) have been associated with the increased incidence of metabolic disorders. In this work, we conducted a systematic review of the literature in order to identify the current knowledge of the interactions between EDCs in food, the gut microbiota, and metabolic disorders in order to shed light on this complex triad. Exposure to EDCs induces a series of changes including microbial dysbiosis and the induction of xenobiotic pathways and associated genes, enzymes, and metabolites involved in EDC metabolism. The products and by-products released following the microbial metabolism of EDCs can be taken up by the host; therefore, changes in the composition of the microbiota and in the production of microbial metabolites could have a major impact on host metabolism and the development of diseases. The remediation of EDC-induced changes in the gut microbiota might represent an alternative course for the treatment and prevention of metabolic diseases.This work was carried out within the frame of GP/EFSA/ENCO/380 2018/03/G04: OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers. This research was also funded by Plan Estatal de I+D+I 2013-2016, Proyecto cofinanciado FEDER-ISCIII PI17/01758, Proyecto cofinanciado FEDER-Consejería de Salud y Familias, Junta de Andalucía PE-0250-2019 and by Fundación Mapfre MAPFRE2018

The Role of Endocrine Disrupting Chemicals in Gestation and Pregnancy Outcomes

This research was funded by the Plan Propio de Investigación de la Universidad de Granada of Spain (grant number PP2022.PP-07). J.M.T. and M.P.-J. are grateful to the Ph.D. Excellence Program “Nutrición y Ciencias de los Alimentos” from the University of Granada. J.M.T. was supported by an FPU contract with grant reference FPU21/04865 funded by the Ministry of Education of Spain.Endocrine disrupting chemicals (EDCs) are exogenous substances widely disseminated both in the environment and in daily-life products which can interfere with the regulation and function of the endocrine system. These substances have gradually entered the food chain, being frequently found in human blood and urine samples. This becomes a particularly serious issue when they reach vulnerable populations such as pregnant women, whose hormones are more unstable and vulnerable to EDCs. The proper formation and activity of the placenta, and therefore embryonic development, may get seriously affected by the presence of these chemicals, augmenting the risk of several pregnancy complications, including intrauterine growth restriction, preterm birth, preeclampsia, and gestational diabetes mellitus, among others. Additionally, some of them also exert a detrimental impact on fertility, thus hindering the reproductive process from the beginning. In several cases, EDCs even induce cross-generational effects, inherited by future generations through epigenetic mechanisms. These are the reasons why a proper understanding of the reproductive and gestational alterations derived from these substances is needed, along with efforts to establish regulations and preventive measures in order to avoid exposition (especially during this particular stage of life).Universidad de Granada PP2022.PP-07Ministry of Education of Spain FPU21/0486

Presence of Parabens and Bisphenols in Food Commonly Consumed in Spain

Given the widespread use of bisphenols and parabens in consumer products, the assessment of their intake is crucial and represents the first step towards the assessment of the potential risks that these compounds may pose to human health. In the present study, a total of 98 samples of food items commonly consumed by the Spanish population were collected from different national supermarkets and grocery stores for the determination of parabens and bisphenols. Our analysis demonstrated that 56 of the 98 food samples contained detectable levels of parabens with limits of quantification (LOQ) between 0.4 and 0.9 ng g-1. The total concentration of parabens (sum of four parabens: åparabens) ranged from below the LOQ to 281.7 ng g-1, with a mean value of 73.86 ng g-1. A total of 52% of the samples showed detectable concentrations of bisphenols. Bisphenol A (BPA) was the most frequently detected bisphenol in the food samples analysed, followed by bisphenol S (BPS) and bisphenol E (BPE). Bisphenol AF (BPAF), bisphenol B (BPB) and bisphenol P (BPP) were not found in any of the analysed samples. LOQ for these bisphenols were between 0.4 and 4.0 ng g-1

Effect of olive oil phenolic compounds on osteoblast differentiation

"This is the peer reviewed version of the following article: Melguizo-Rodríguez L., Manzano-Moreno F.J., De Luna-Bertos E., Rivas A., Ramos-Torrecillas J., Ruiz C., García-Martínez O. Effect of olive oil phenolic compounds on osteoblast differentiation. European Journal of Clinical Investigation, 2018; 48(4): 1-6, which has been published in final form at 10.1111/eci.12904. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited."Background: Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes individuals to an increased risk of fracture. Previous in vivo and in vitro studies have reported that phenolic compounds present in extra virgin olive oil have a beneficial effect on osteoblasts in terms of increase cell proliferation. The aim of this study was to determine whether phenolic compounds present in olive oil could modify the expression of cell differentiation markers on osteoblasts. Study Design: An in vitro experimental design was peformed using MG-63 osteoblasts cell line. Methods: MG63 cells were exposed to different doses of luteolin, apigenin, or p-coumaric, caffeic, or ferulic acid. Alkaline phosphatase (ALP) was evaluated by spectrophotometry and antigen expression (CD54, CD80, CD86, and HLA-DR) by flow cytometry. Results: At 24 h, treated groups showed an increased ALP and modulated antigen profile, with respect to the non-treated group. Conclusion: These results demonstrate that the phenolic compounds studied induce cell maturation in vitro, increasing ALP synthesis and reducing the expression of antigens involved in immune functions of the osteoblast which would improve bone density.GRUPO BIO-27

Phenolic compounds in extra virgin olive oil stimulate human osteoblastic cell proliferation

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11–16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18–22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9–13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly

Bisphenol A Analogues in Food and Their Hormonal and Obesogenic Effects: A Review

Bisphenol A (BPA) is the most well-known compound from the bisphenol family. As BPA has recently come under pressure, it is being replaced by compounds very similar in structure, but data on the occurrence of these BPA analogues in food and human matrices are limited. The main objective of this work was to investigate human exposure to BPA and analogues and the associated health effects. We performed a literature review of the available research made in humans, in in vivo and in vitro tests. The findings support the idea that exposure to BPA analogues may have an impact on human health, especially in terms of obesity and other adverse health effects in children.This research was funded by Plan Estatal de I+D+I 2013-2016 Proyecto cofinanciado FEDER-ISCIII PI17/01758 and by Fundación Mapfre MAPFRE2018

Next Generation Probiotics for Neutralizing Obesogenic Effects: Taxa Culturing Searching Strategies

This work was carried out within the frame of GP/EFSA/ENCO/380 2018/03/G04: OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers. This research was also funded by FEDER-Infrastructure: IE_2019-198. A.L-M Incentivacion de la Investigacion. Plan Propio-UGR. K. Cerk is collaborating with UGR under the EU-FORA Programme (2020/2021).The combination of diet, lifestyle, and the exposure to food obesogens categorized into "microbiota disrupting chemicals" (MDC) could determine obesogenic-related dysbiosis and modify the microbiota diversity that impacts on individual health-disease balances, inducing altered pathogenesis phenotypes. Specific, complementary, and combined treatments are needed to face these altered microbial patterns and the specific misbalances triggered. In this sense, searching for next-generation beneficial microbes or next-generation probiotics (NGP) by microbiota culturing, and focusing on their demonstrated, extensive scope and well-defined functions could contribute to counteracting and repairing the effects of obesogens. Therefore, this review presents a perspective through compiling information and key strategies for directed searching and culturing of NGP that could be administered for obesity and endocrine-related dysbiosis by (i) observing the differential abundance of specific microbiota taxa in obesity-related patients and analyzing their functional roles, (ii) developing microbiota-directed strategies for culturing these taxa groups, and (iii) applying the successful compiled criteria from recent NGP clinical studies. New isolated or cultivable microorganisms from healthy gut microbiota specifically related to obesogens' neutralization effects might be used as an NGP single strain or in consortia, both presenting functions and the ability to palliate metabolic-related disorders. Identification of holistic approaches for searching and using potential NGP, key aspects, the bias, gaps, and proposals of solutions are also considered in this review.OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers GP/EFSA/ENCO/380 2018/03/G04FEDER-Infrastructure IE_2019-19

Dietary exposure to parabens and body mass index in an adolescent Spanish population

This work was carried out in line with 'GP/EFSA/ENCO/380 2018/03/G04: OBEMIRISK: Knowledge platform for assessing the risk of Bisphenols on gut microbiota and its role in obesogenic phenotype: looking for biomarkers'. This research was also funded by Plan Estatal de I + D + I 2013-2016 and co-funded by FEDER-ISCIII PI17/01758, FEDER-Consejeria de Salud y Familias, Junta de Andalucia PE-0250-2019, FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades/Proyecto P18-RT-4247. All individuals participating in this research signed an informed consent form and the study protocol was approved by the Ethics Com-mittee of the University of Granada.Parabens are alkyl esters of p-hydroxybenzoic acid which are extensively used in cosmetics, pharmaceuticals and foodstuffs due to their antimicrobial properties. The most commonly used parabens are methyl-(MeP), ethyl- (EtP), propyl-(PrP) and butyl-(BuP) paraben. Most human exposure to parabens is achieved through the consumption of food or pharmaceutical products and the use of personal care products. However, studies on dietary parabens exposure and the associated factors are very scarce. The main aim of the present study was to explore factors associated with dietary exposure to parabens in Spanish adolescents according to gender. Dietary data and anthropometric measures were collected from 585 adolescents (53.4% boys) aged 12–16 years. Parabens exposure through diet was assessed using a food frequency questionnaire with food products providing more than 95% of energy and macronutrient intake being included in analysis. Stepwise regression was used to identify the foods that most contributed to parabens intake. Logistic regression was used to evaluate factors predicting higher dietary exposure to parabens. The main contributors to dietary MeP, EtP, PrP and BuP exposure in adolescent boys were eggs (41.9%), canned tuna (46.4%), bakery and baked goods products (57.3%) and pineapple (61.1%). In adolescent girls, the main contributors were apples and pears (35.3%), canned tuna (42.1%), bakery and baked goods products (55.1%) and olives (62.1%). Overweight/obese girls were more likely to belong to the highest tertile of overall parabens intake (odds ratio [OR]: 3.32; 95% confidence interval [95% CI]: 1.21–9.15) and MeP (OR: 3.05; 95% CI: 1.14–8.12) than those with a body mass index lower than 25 kg/m2. These findings suggest a positive association between dietary exposure to parabens and overweight/obesity in adolescent girls.Plan Estatal de I + D + I 2013-2016FEDER-ISCIII PI17/01758FEDER-Consejeria de Salud y FamiliasJunta de Andalucia PE-0250-2019FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades/Proyecto P18-RT-424

Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study

Introduction: A growing number of studies link the increase in overweight/ obesity worldwide to exposure to certain environmental chemical pollutants that display obesogenic activity (obesogens). Since exposure to obesogens during the first stages of life has been shown to have a more intense and pronounced effect at lower doses, it is imperative to study their possible effects in childhood. The objective here was to study the association of Bisphenol A (BPA) and 11 BPA analogs in children, using three biological matrices (nails, saliva and urine), and overweight and obesity (n = 160). Methods: In this case–control study, 59 overweight/obese children and 101 controls were included. The measuring of Bisphenols in the matrices was carried out by ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to study the association between overweight/obesity and Bisphenol exposure. Results: The results suggested that BPF in nails is associated with overweight/ obesity in children (OR:4.87; p = 0.020). In saliva, however, the highest detected concentrations of BPAF presented an inverse association (OR: 0.06; p = 0.010) with overweight/obesity. No associations of statistical significance were detected between exposure to BPA or its other analogs and overweight/obesity in any of the biological matrices.FEDER-Consejería de Salud y Familias’ of the Junta de Andalucía PE-0250-201