Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80

Background The rising prevalence of many chronic diseases related to gut barrier dysfunction coincides with the increased global usage of dietary emulsifiers in recent decades. We therefore investigated the effect of the frequently used food emulsifiers on cytotoxicity, barrier function, transcriptome alterations, and protein expression in gastrointestinal epithelial cells. Methods Human intestinal organoids originating from induced pluripotent stem cells, colon organoid organ‐on‐a‐chip, and liquid–liquid interface cells were cultured in the presence of two common emulsifiers: polysorbate 20 (P20) and polysorbate 80 (P80). The cytotoxicity, transepithelial electrical resistance (TEER), and paracellular‐flux were measured. Immunofluorescence staining of epithelial tight‐junctions (TJ), RNA‐seq transcriptome, and targeted proteomics were performed. Results Cells showed lysis in response to P20 and P80 exposure starting at a 0.1% (v/v) concentration across all models. Epithelial barrier disruption correlated with decreased TEER, increased paracellular‐flux and irregular TJ immunostaining. RNA‐seq and targeted proteomics analyses demonstrated upregulation of cell development, signaling, proliferation, apoptosis, inflammatory response, and response to stress at 0.05%, a concentration lower than direct cell toxicity. A proinflammatory response was characterized by the secretion of several cytokines and chemokines, interaction with their receptors, and PI3K‐Akt and MAPK signaling pathways. CXCL5, CXCL10, and VEGFA were upregulated in response to P20 and CXCL1, CXCL8 (IL‐8), CXCL10, LIF in response to P80. Conclusions The present study provides direct evidence on the detrimental effects of food emulsifiers P20 and P80 on intestinal epithelial integrity. The underlying mechanism of epithelial barrier disruption was cell death at concentrations between 1% and 0.1%. Even at concentrations lower than 0.1%, these polysorbates induced a proinflammatory response suggesting a detrimental effect on gastrointestinal health

Vaccines and allergic reactions:The past, the current COVID-19 pandemic, and future perspectives

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.</p

Calcium supplementation does not alter lipid oxidation or lipolysis in overweight/obese women.

Based on cell culture and studies in mice, increased dietary calcium appears to stimulate lipolysis and could possibly reduce body adiposity through hormonal influences on adipocyte calcium uptake. In this study, we investigated the effects of 1,500 mg supplemental calcium daily for 3 months on hormones regulating calcium and energy metabolism and rates of lipid oxidation and lipolysis in overweight women. Fifteen overweight (BMI &gt; 25 kg/m(2)) premenopausal women were supplemented with 1,500 mg of calcium, as CaCO(3), per day for 3 months while maintaining their usual diets and activity levels. Baseline and endpoint measurements were obtained after the subjects consumed a standardized 25% fat diet for 4 days. Lipid oxidation was measured by indirect calorimetry, lipolysis by infusion of deuterated glycerol, and body fat by dual-energy X-ray absorptiometry. Urinary calcium, circulating levels of hormones involved in energy and lipid metabolism (insulin, leptin, and adiponectin) or calcium metabolism (25(OH)D, 1,25(OH)(2)D), and parathyroid hormone (PTH)) were also measured. Urinary levels of calcium (P = 0.005) increased and 1,25(OH)(2)D declined (P = 0.03). However other parameters, including body weight, body fat, PTH, insulin, leptin, adiponectin, 25(OH)D, as well as rates of lipid oxidation and lipolysis were not altered by calcium supplementation. Calcium supplementation for 3 months increased urinary calcium excretion, decreased circulating levels of 1,25(OH)(2)-D, but had no effect on rates of lipid oxidation or lipolysis, in these overweight women

Food allergy across the globe

The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines. Keywords: Food allergy; epidemiology; guidelines; prevention; treatment

Neuroimmunology and Allergic Disease

The prevalence of allergic diseases is rising globally, inducing heavy quality of life and economic burdens. Allergic reactions are mediated by the complex bi-directional cross-talk between immune and nervous systems that we are only beginning to understand. Here, we discuss our current understanding of the molecular mechanisms of how this cross-talk occurs in the skin, gut, and lungs. An improved understanding of the communication between the immune and nervous system may lead to the development of novel therapies for allergic diseases

Increased duration of pollen and mold exposure are linked to climate change

Abstract Pollen and molds are environmental allergens that are affected by climate change. As pollen and molds exhibit geographical variations, we sought to understand the impact of climate change (temperature, carbon dioxide (CO2), precipitation, smoke exposure) on common pollen and molds in the San Francisco Bay Area, one of the largest urban areas in the United States. When using time-series regression models between 2002 and 2019, the annual average number of weeks with pollen concentrations higher than zero increased over time. For tree pollens, the average increase in this duration was 0.47 weeks and 0.51 weeks for mold spores. Associations between mold, pollen and meteorological data (e.g., precipitation, temperature, atmospheric CO2, and area covered by wildfire smoke) were analyzed using the autoregressive integrated moving average model. We found that peak concentrations of weed and tree pollens were positively associated with temperature (p < 0.05 at lag 0–1, 0–4, and 0–12 weeks) and precipitation (p < 0.05 at lag 0–4, 0–12, and 0–24 weeks) changes, respectively. We did not find clear associations between pollen concentrations and CO2 levels or wildfire smoke exposure. This study’s findings suggest that spore and pollen activities are related to changes in observed climate change variables

Vaccines and allergic reactions: The past, the current COVID‐19 pandemic, and future perspectives

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research

Allergy: Mechanistic insights into new methods of prevention and therapy

In the past few decades, the prevalence of allergic diseases has increased worldwide. Here, we review the etiology and pathophysiology of allergic diseases, including the role of the epithelial barrier, the immune system, climate change, and pollutants. Our current understanding of the roles of early life and infancy; diverse diet; skin, respiratory, and gut barriers; and microbiome in building immune tolerance to common environmental allergens has led to changes in prevention guidelines. Recent developments on the mechanisms involved in allergic diseases have been translated to effective treatments, particularly in the past 5 years, with additional treatments now in advanced clinical trials