scholarly journals Can Exposure to Environmental Chemicals Increase the Risk of Diabetes Type 1 Development?

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Johanna Bodin ◽  
Lars Christian Stene ◽  
Unni Cecilie Nygaard
Keyword(s):  
Environmental Factors ◽  
Immune Cell ◽  
Pancreatic Beta Cell ◽  
Environmental Pollutants ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Negative Effects ◽  
Environmental Chemical ◽  
Cell Functions

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged.

Exposure to environmental chemicals and type 1 diabetes: an update

2019 ◽  
Vol 73 (6) ◽  
pp. 483-488 ◽  
Author(s):  
Sarah G Howard
Keyword(s):  
Type 1 Diabetes ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Environmental Chemicals ◽  
Exposure Level ◽  
Environmental Chemical ◽  
Timing Of Exposure

This narrative review summarises recently published epidemiological and in vivo experimental studies on exposure to environmental chemicals and their potential role in the development of type 1 diabetes mellitus (T1DM). These studies focus on a variety of environmental chemical exposures, including to air pollution, arsenic, some persistent organic pollutants, pesticides, bisphenol A and phthalates. Of the 15 epidemiological studies identified, 14 include measurements of exposures during childhood, 2 include prenatal exposures and 1 includes adults over age 21. Together, they illustrate that the role of chemicals in T1DM may be complex and may depend on a variety of factors, such as exposure level, timing of exposure, nutritional status and chemical metabolism. While the evidence that these exposures may increase the risk of T1DM is still preliminary, it is critical to investigate this possibility further as a means of preventing T1DM.

scholarly journals Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Ming Lei ◽  
Rani Menon ◽  
Sara Manteiga ◽  
Nicholas Alden ◽  
Carrie Hunt ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodevelopmental Disorders ◽  
Developmental Disorders ◽  
Chemical Exposure ◽  
Metabolite Profile ◽  
Environmental Chemicals ◽  
Toxic Metabolite ◽  
Environmental Chemical ◽  
Diethylhexyl Phthalate

ABSTRACT Exposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl phthalate (DEHP), a ubiquitous plasticizer implicated in neurodevelopmental disorders, on the composition and metabolite outputs of gut microbiota in young mice. Administration of DEHP by oral gavage increased the abundance of Lachnoclostridium, while decreasing Clostridium sensu stricto. Addition of DEHP to in vitro-cultured cecal microbiota increased the abundance of Paenibacillus and Lachnoclostridium. Untargeted metabolomics showed that DEHP broadly altered the metabolite profile in the culture. Notably, DEHP enhanced the production of p-cresol while inhibiting butyrate synthesis. Metabolic model-guided correlation analysis indicated that the likely sources of p-cresol are Clostridium species. Monoculture of Lachnoclostridium bolteae confirmed that it is capable of producing p-hydroxyphenylacetic acid, the immediate precursor of p-cresol, and that the species’ growth is enhanced upon DEHP exposure. Taken together, these findings suggest a model where DEHP increases production of p-cresol, a bacterial metabolite linked with neurodevelopmental disorders, by expanding the abundance of species that synthesize the metabolite’s precursor. IMPORTANCE Several previous studies have pointed to environmental chemical exposure during windows of development as a contributing factor in neurodevelopmental disorders and correlated these disorders with microbiota dysbiosis; however, little is known about how the chemicals specifically alter the microbiota to interfere with development. The findings reported in this paper unambiguously establish that a pollutant linked with neurodevelopmental disorders can directly modify the microbiota to promote the production of a potentially toxic metabolite (p-cresol) that has also been correlated with neurodevelopmental disorders. Furthermore, we used a novel modeling strategy to identify the responsible enzymes and bacterial sources of this metabolite. To the best of our knowledge, the present study is the first to characterize the functional consequence of phthalate exposure on a developed microbiota. Our results suggest that specific bacterial pathways could be developed as diagnostic and therapeutic targets against health risks posed by ingestion of environmental chemicals.

scholarly journals Lights, Chemicals, Action: Studying Red Worms’ Responses to Environmental Contaminants

2016 ◽  
Vol 78 (7) ◽  
pp. 591-598
Author(s):  
Daniel N. Weber ◽  
Renee A. Hesselbach ◽  
David H. Petering ◽  
Louise P. Petering ◽  
Craig A. Berg
Keyword(s):  
High School ◽  
High School Students ◽  
Environmental Science ◽  
Environmental Pollutants ◽  
Chemical Exposure ◽  
School Curriculum ◽  
Environmental Chemicals ◽  
Science Content ◽  
School Students ◽  
Environmental Agents

We have developed an experimental module that introduces high school students to guided scientific inquiry. It is designed to incorporate environmental health and ecological concepts into the basic biology or environmental-science content of the high school curriculum. Using the red worm, a familiar live species that is amenable to classroom experimentation, students learn how environmental agents affect the animal's locomotion by altering sensory neuron–muscle interactions and, as a result, influence its distribution in nature. In turn, the results of these experiments have direct application to human-caused environmental disruptions that cause changes in species distribution and indirectly increase the recognition that environmental chemicals affect human health. Students undertake a series of explorations to identify how red worms sense their environment and then apply that knowledge to understand the effects of chemical exposure on locomotor behavior. The activities are designed to generate critical thinking about neuromuscular processes and environmental pollutants that affect them.

scholarly journals PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation

2020 ◽  
Author(s):  
Neelakanteswar Aluru ◽  
Sibel I Karchner
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Rna Modifications ◽  
Environmental Chemical ◽  
Stop Codons ◽  
Developmental Gene Expression

AbstractChemical modifications of proteins, DNA and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests these RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3’ UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 hours starting from 72 hours post-fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (FDR 5%), respectively. The majority of the peaks were preferentially located around the 3’UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (e.g., ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, foxi1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

scholarly journals Particle Uptake Driven Phagocytosis in Macrophages and Neutrophils Enhances Bacterial Clearance

2021 ◽  
Author(s):  
Preeti Sharma ◽  
Anjali Vijaykumar ◽  
Jayashree Vijaya Raghavan ◽  
Supriya Rajendra Rananaware ◽  
Alakesh Alakesh ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Environmental Pollutants ◽  
Base Material ◽  
Cellular Heterogeneity ◽  
E Coli ◽  
Phagocytic Ability ◽  
Particle Uptake ◽  
Cell Functions ◽  
Free Particles

AbstractHumans are exposed to numerous synthetic foreign particulates in the form of environmental pollutants and diagnostic or therapeutic agents. Specialized immune cells (phagocytes) clear these particulates by phagocytosing and attempting to degrade them. The process of recognition and internalization of the particulates may trigger changes in the function of phagocytes. Some of these changes, especially the ability of a particle-loaded phagocyte to take up and neutralize pathogens, remains poorly studied. Herein, we demonstrate that the uptake of non-stimulatory cargo-free particles enhances the phagocytic ability of monocytes, macrophages and neutrophils. The enhancement in phagocytic ability was independent of particle properties, such as size or the base material constituting the particle. Additionally, we show that the increased phagocytosis was not a result of cellular activation or cellular heterogeneity but was driven by changes in cell membrane fluidity and cellular compliance. A consequence of the enhanced phagocytic activity was that particulate-laden immune cells neutralize E. coli faster in culture. Moreover, when administered in mice as a prophylactic, particulates enable faster clearance of E. coli and S. epidermidis. Together, we demonstrate that the process of uptake induces cellular changes that favor additional phagocytic events. This study provides insights into using non-stimulatory cargo-free particles to engineer immune cell functions for applications involving faster clearance of phagocytosable particulates.

scholarly journals PCB126 Exposure Revealed Alterations in m6A RNA Modifications in Transcripts Associated With AHR Activation

2020 ◽  
Author(s):  
Neelakanteswar Aluru ◽  
Sibel I Karchner
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Rna Modifications ◽  
Environmental Chemical ◽  
Stop Codons ◽  
Developmental Gene Expression

Abstract Chemical modifications of proteins, DNA, and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests the RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3′ UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 h starting from 72 h post fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (false discovery rate 5%), respectively. The majority of the peaks were preferentially located around the 3′ UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (eg, ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, sned1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

scholarly journals Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions

2019 ◽  
Vol 10 ◽  
Author(s):  
James A. Pearson ◽  
Ningwen Tai ◽  
Dilrukshi K. Ekanayake-Alper ◽  
Jian Peng ◽  
Youjia Hu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Intestinal Microbiota ◽  
Immune Cell ◽  
Cell Functions

scholarly journals Lipophilic chemical exposure as a cause of cardiovascular disease

2013 ◽  
Vol 6 (2) ◽  
pp. 55-62 ◽  
Author(s):  
Harold I. Zeliger
Keyword(s):  
Cardiovascular Disease ◽  
Developmental Disorders ◽  
Metabolic Disorders ◽  
Chemical Properties ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Low Molecular Weight ◽  
Endocrine Disorders ◽  
Environmental Chemical

Abstract Environmental chemical exposure has been linked to numerous diseases in humans. These diseases include cancers; neurological and neurodegenerative diseases; metabolic disorders including type 2 diabetes, metabolic syndrome and obesity; reproductive and developmental disorders; and endocrine disorders. Many studies have associated the link between exposures to environmental chemicals and cardiovascular disease (CVD). These chemicals include persistent organic pollutants (POPs); the plastic exudates bisphenol A and phthalates; low molecular weight hydrocarbons (LMWHCs); and poly nuclear aromatic hydrocarbons (PAHs). Here it is reported that though the chemicals reported on differ widely in chemical properties and known points of attack in humans, a common link exists between them. All are lipophilic species that are found in serum. Environmentally induced CVD is related to total lipophilic chemical load in the blood. Lipophiles serve to promote the absorption of otherwise not absorbed toxic hydrophilic species that promote CVD.

scholarly journals From Extrapolation to Precision Chemical Hazard Assessment: The Ecdysone Receptor Case Study

Toxics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Raquel Ruivo ◽  
João Sousa ◽  
Teresa Neuparth ◽  
Olivier Geffard ◽  
Arnaud Chaumot ◽  
...  
Keyword(s):  
Hazard Assessment ◽  
Functional Characterization ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Current Evidence ◽  
Ecdysone Receptor ◽  
Environmental Chemical ◽  
Chemical Action ◽  
Assessment Strategies

Hazard assessment strategies are often supported by extrapolation of damage probabilities, regarding chemical action and species susceptibilities. Yet, growing evidence suggests that an adequate sampling of physiological responses across a representative taxonomic scope is of paramount importance. This is particularly relevant for Nuclear Receptors (NR), a family of transcription factors, often triggered by ligands and thus, commonly exploited by environmental chemicals. Within NRs, the ligand-induced Ecdysone Receptor (EcR) provides a remarkable example. Long regarded as arthropod specific, this receptor has been extensively targeted by pesticides, seemingly innocuous to non-target organisms. Yet, current evidence clearly suggests a wider presence of EcR orthologues across metazoan lineages, with unknown physiological consequences. Here, we address the state-of-the-art regarding the phylogenetic distribution and functional characterization of metazoan EcRs and provide a critical analysis of the potential disruption of such EcRs by environmental chemical exposure. Using EcR as a case study, hazard assessment strategies are also discussed in view of the development of a novel “precision hazard assessment paradigm.

scholarly journals Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreatic β-Cell Function

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Nina Mickelson Weldingh ◽  
Lena Jørgensen-Kaur ◽  
Rune Becher ◽  
Jørn A. Holme ◽  
Johanna Bodin ◽  
...  
Keyword(s):  
Cell Death ◽  
Insulin Secretion ◽  
Bisphenol A ◽  
Cell Function ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Environmental Chemical ◽  
Simultaneous Exposure ◽  
Phthalate Metabolites ◽  
Β Cell Function

Bisphenol A (BPA) and phthalates are common environmental contaminants that have been proposed to influence incidence and development of types 1 and 2 diabetes. Thus, effects of BPA and three phthalate metabolites (monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP)) were studied in the pancreatic β-cell line INS-1E, after 2–72 h of exposure to 5–500 μM. Three endpoints relevant to accelerated development of types 1 or 2 diabetes were investigated: β-cell viability, glucose-induced insulin secretion, and β-cell susceptibility to cytokine-induced cell death. BPA and the phthalate metabolites reduced cellular viability after 72 h of exposure, with BPA as the most potent chemical. Moreover, BPA, MEHP, and MnBP increased insulin secretion after 2 h of simultaneous exposure to chemicals and glucose, with potency BPA > MEHP > MnBP. Longer chemical exposures (24–72 h) showed no consistent effects on glucose-induced insulin secretion, and none of the environmental chemicals affected susceptibility to cytokine-induced cell death. Overall, BPA was more potent than the investigated phthalate metabolites in affecting insulin secretion and viability in the INS-1E pancreatic β-cells. In contrast to recent literature, concentrations with relevance to human exposures (1–500 nM) did not affect the investigated endpoints, suggesting that this experimental model displayed relatively low sensitivity to environmental chemical exposure.

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