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

Air pollution and endocrine disruptors induce human microbiome imbalances: A systematic review of recent evidence and possible biological mechanisms

A rich body of literature indicates that environmental factors interact with the human microbiome and influence its composition and functions contributing to the pathogenesis of diseases in distal sites of the body. This systematic review examines the scientific evidence on the effect of environmental toxicants, air pollutants and endocrine disruptors (EDCs), on compositional and diversity of human microbiota. Articles from PubMed, Embase, WoS and Google Scholar where included if they focused on human populations or the SHIME® model, and assessed the effects of air pollutants and EDCs on human microbiome. Non-human studies, not written in English and not displaying original research were excluded. The Newcastle-Ottawa Scale was used to assess the quality of individual studies. Results were extracted and presented in tables. 31 studies were selected, including 24 related to air pollutants, 5 related to EDCs, and 2 related to EDC using the SHIME® model. 19 studies focussed on the respiratory system (19), gut (8), skin (2), vaginal (1) and mammary (1) microbiomes. No sufficient number of studies are available to observe a consistent trend for most of the microbiota, except for streptococcus and veillionellales for which 9 out of 10, and 3 out of 4 studies suggest an increase of abundance with exposure to air pollution. A limitation of the evidence reviewed is the scarcity of existing studies assessing microbiomes from individual systems. Growing evidence suggests that exposure to environmental contaminants could change the diversity and abundance of resident microbiota, e.g. in the upper and lower respiratory, gastrointestinal, and female reproductive system. Microbial dysbiosis might lead to colonization of pathogens and outgrowth of pathobionts facilitating infectious diseases. It also might prime metabolic dysfunctions disrupting the production of beneficial metabolites. Further studies should elucidate the role of environmental pollutants in the development of dysbiosis and dysregulation of microbiota-related immunological processes.Funding for open access charge: CRUE-Universitat Jaume

Endocrine Aspects of Environmental "Obesogen" Pollutants

Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called "obesogenic environment". Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity

Neurotoxins and Autism

Recently, a great concern has risen about the increasing prevalence of autism as a neurodevelopmental disorder. Environmental factors as significant contributors to children’s health through a wide range of routes are linked to remarkable increases in this disorder. It is well known and accepted that young children are more vulnerable to environmental toxins, compared to adults. Modern day lifestyles with more mercury and lead exposures, fast food, cell phones, and microwaves place children at higher risk of neurotoxicity. Moreover, a huge number of synthetic chemicals termed as high-production-volume (HPV) chemicals are found in many products such as medications, cosmetics, building materials, plastic, and car fuels. These HPVs highly contribute to brain damage in developing infants. Other environmental toxins include thalidomide, valproic acid, misoprostol, and many infectious agents among which are pathogenic bacteria or their metabolites are found to be neurotoxic and/or linked to incidences of autism. This chapter summarizes the most important routes of exposure to environmental neurotoxins and explains how these toxins are related to the remarkable increase in the prevalence of autism through different etiological mechanisms such as oxidative stress, neuroinflammation, impaired neurochemistry and glutamate excitotoxicity

Endocrine Disrupting Chemicals and Type 1 Diabetes

Type 1 diabetes (T1D) is the most common chronic metabolic disease in children and adolescents. The etiology of T1D is not fully understood but it seems multifactorial. The genetic background determines the predisposition to develop T1D, while the autoimmune process against -cells seems to be also determined by environmental triggers, such as endocrine disrupting chemicals (EDCs). Environmental EDCs may act throughout dierent temporal windows as single chemical agent or as chemical mixtures. They could aect the development and the function of the immune system or of the beta-cells function, promoting autoimmunity and increasing the susceptibility to autoimmune attack. Human studies evaluating the potential role of exposure to EDCs on the pathogenesis of T1D are few and demonstrated contradictory results. The aim of this narrative review is to summarize experimental and epidemiological studies on the potential role of exposure to EDCs in the development of T1D.We highlight what we know by animals about EDCs\u2019 eects on mechanisms leading to T1D development and progression. Studies evaluating the EDC levels in patients with T1D were also reported. Moreover, we discussed why further studies are needed and how they should be designed to better understand the causal mechanisms and the next prevention interventions

Inflammatory bowel disease: New insights into the interplay between environmental factors and pparγ

The pathophysiological processes of inflammatory bowel diseases (IBDs), i.e., Crohn’s disease (CD) and ulcerative colitis (UC), are still not completely understood. The exact etiology re-mains unknown, but it is well established that the pathogenesis of the inflammatory lesions is due to a dysregulation of the gut immune system resulting in over-production of pro-inflammatory cy-tokines. Increasing evidence underlines the involvement of both environmental and genetic factors. Regarding the environment, the microbiota seems to play a crucial role. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that exert pleiotropic effects on glucose homeo-stasis, lipid metabolism, inflammatory/immune processes, cell proliferation, and fibrosis. Further-more, PPARs modulate interactions with several environmental factors, including microbiota. A significantly impaired PPARγ expression was observed in UC patients’ colonic epithelial cells, suggesting that the disruption of PPARγ signaling may represent a critical step of the IBD pathogenesis. This paper will focus on the role of PPARγ in the interaction between environmental factors and IBD, and it will analyze the most suitable in vitro and in vivo models available to better study these relationships

Environmental Obesogens and Human Health

Obesity is an alarming public health concern that contributes to a substantially increased risk of multiple chronic disorders, including diabetes. As per WHO data, in 2016, almost 39% adult population of the world is overweight, 13% of them were obese. There is prominent evidence on the involvement of environmental endocrine-disrupting chemicals, termed obesogens, in the prevalence of this growing worldwide pandemic, obesity. The exaggerated effect of obesogens on endocrine disruption, lipid metabolism and homeostasis, adipocyte functioning, impaired thermogenesis, inflammation, epigenetics, and overall human health will be covered in this chapter. This chapter will discuss the environmental obesogen hypothesis, the epidemiological and experimental evidence of obesogens, its chemical characteristics, and possible mechanism of actions. It will also focus on some recent indications of obesogens and their correlation in COVID-19 disease pathogenesis. This chapter will try to conclude with strategies for identifying the underlying mechanisms of obesogens within model systems and the human body, including future directions

Environmental Epigenetics and Obesity

In recent years, increasing interest on the effects of dietary components on epigenetic processes and, consequently, on the regulation of gene expression and metabolic responses has led clinical efforts worldwide to approach obesity. When inadequate, food consumption leads to chronic and non-communicable diseases (CNCD) including obesity. Among the dynamic changes in cellular responses by nutritional interventions, epigenetic control represents a master regulator underlying both positive and negative effects of diet on body mass, including DNA methylation, histone post-translational modifications and microRNA expression signatures. Indeed, mechanistical studies of the relationship between environment, diet and differential epigenetic landscapes are gaining attention on functional pathways involved in cell growth, DNA-repair, lipogenesis, senescence, inflammation, tumor suppression, apoptosis and oncogenesis. Being the dynamic interplay between epigenetics and obesity so complex, moreover considering a detrimental environment context, this chapter will discuss the state-of-the-art evidence showing the pollution impact on the different epigenetic mechanisms regulating an obese phenotype, and how these molecular events determine the organic interplay upon metabolic alterations, and finally we will introduce recent epidrugs and biocompounds of therapeutic interests due to their potential to modulate and even revert obesity-inducing epigenetic mechanisms

Probiotic administration mitigates bisphenol a reproductive toxicity in zebrafish

none5siAlthough the use of bisphenol A (BPA) has been banned in a number of countries, its presence in the environment still creates health issues both for humans and wildlife. So far, BPA toxicity has been largely investigated on different biological processes, from reproduction to development, immune system, and metabolism. In zebrafish, Danio rerio, previous studies revealed the ability of environmentally relevant concentrations of this contaminant to significantly impair fertility via epigenetic modification. In addition, several studies demonstrated the ability of different probiotic strains to improve organism health. This study provides information on the role of the probiotic mixture SLAb51 to counteract adverse BPA effects on reproduction. A 28‐day trial was set up with different experimental groups: BPA, exposed to 10 μg/L BPA; P, receiving a dietary supplementation of SLAb51 at a final concentration of 109 CFU/g; BPA+P exposed to 10 μg/L BPA and receiving SLAb51 at a final concentration of 109 CFU/g and a C group. Since oocyte growth and maturation represent key aspects for fertility in females, studies were performed on isolated class III (vitellogenic) and IV (in maturation) follicles and liver, with emphasis on the modulation of the different vitellogenin isoforms. In males, key signals regulating spermatogenesis were investigated. Results demonstrated that in fish exposed to the combination of BPA and probiotic, most of the transcripts were closer to C or P levels, supporting the hypothesis of SLAb51 to antagonize BPA toxicity. This study represents the first evidence related to the use of SLAb51 to improve reproduction and open new fields of investigation regarding its use to reduce endocrine disrupting compound impacts on health.openGiommi C.; Habibi H.R.; Candelma M.; Carnevali O.; Maradonna F.Giommi, C.; Habibi, H. R.; Candelma, M.; Carnevali, O.; Maradonna, F