From human herpes virus-6 reactivation to autoimmune reactivity against tight junctions and neuronal antigens, to inflammation, depression, and chronic fatigue syndrome due to Long COVID.

Inflammation and autoimmune responses contribute to the pathophysiology of Long COVID, and its affective and chronic fatigue syndrome symptoms, labeled "the physio-affective phenome." To investigate whether Long COVID and its physio-affective phenome are linked to autoimmunity to the tight junction proteins, zonulin and occludin (ZOOC), and immune reactivity to lipopolysaccharides (LPS), and whether the latter are associated with signs of human herpes virus-6 (HHV-6) reactivation, autoimmunity directed against oligodendrocyte and neuronal proteins, including myelin basic protein. IgA/IgM/IgG responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), HHV-6, ZOOC, and neuronal proteins, C-reactive protein (CRP), and advanced oxidation protein products (AOPPs), were measured in 90 Long COVID patients and 90 healthy controls. The physio-affective phenome was conceptualized as a factor extracted from physical and affective symptom domains. Neural network identified IgA directed to LPS (IgA-LPS), IgG-ZOOC, IgG-LPS, and IgA-ZOOC as important variables associated with Long COVID diagnosis with an area under the ROC curve of 0.755. Partial Least Squares analysis showed that 40.9% of the variance in the physio-affective phenome was explained by CRP, IgA-myelin basic protein (MBP), and IgG-MBP. A large part of the variances in both autoimmune responses to MBP (36.3%-39.7%) was explained by autoimmunity (IgA and IgG) directed to ZOOC. The latter was strongly associated with indicants of HHV-6 reactivation, which in turn was associated with increased IgM-SARS-CoV-2. Autoimmunity against components of the tight junctions and increased bacterial translocation may be involved in the pathophysiology of Long COVID's physio-affective phenome.

Immune activation and immune-associated neurotoxicity in Long-COVID: A systematic review and meta-analysis of 103 studies comprising 58 cytokines/chemokines/growth factors.

BACKGROUND: Multiple studies have shown that Long COVID (LC) disease is associated with heightened immune activation, as evidenced by elevated levels of inflammatory mediators. However, there is no comprehensive meta-analysis focusing on activation of the immune inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS) along with other immune phenotypes in LC patients. OBJECTIVES: This meta-analysis is designed to explore the IRS and CIRS profiles in LC patients, the individual cytokines, chemokines, growth factors, along with C-reactive protein (CRP) and immune-associated neurotoxicity. METHODS: To gather relevant studies for our research, we conducted a thorough search using databases such as PubMed, Google Scholar, and SciFinder, covering all available literature up to July 5th, 2024. RESULTS: The current meta-analysis encompassed 103 studies that examined multiple immune profiles, C-reactive protein, and 58 cytokines/chemokines/growth factors in 5502 LC patients versus 5962 normal controls (NC). LC patients showed significant increases in IRS/CIRS ratio (standardized mean difference (SMD: 0.156, confidence interval (CI): 0.062;0.250), IRS (SMD: 0.338, CI: 0.236;0.440), M1 macrophage (SMD: 0.371, CI: 0.263;0.480), T helper (Th)1 (SMD: 0.316, CI: 0.185;0.446), Th17 (SMD: 0.439, CI: 0.302;0.577) and immune-associated neurotoxicity (SMD: 0.384, CI: 0.271;0.497). In addition, CRP and 21 different cytokines displayed significantly elevated levels in LC patients compared to NC. CONCLUSION: LC disease is characterized by IRS activation and increased immune-associated neurotoxicity.

Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome.

BACKGROUND: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. OBJECTIVES: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. METHODS: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5'-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). RESULTS: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709). CONCLUSION: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.

Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients in a cohort of 231 individuals, of which 161 were COVID-19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID-19 infection. Autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations while stratifying COVID-19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID-19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID-19. This work maps the intersection of COVID-19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS-CoV-2 infection. Thus, this cross-sectional study suggests that SARS-CoV-2 infection induces autoantibody signatures associated with COVID-19 severity and several autoantibodies that can be used as biomarkers of COVID-19 severity, indicating autoantibodies as potential therapeutical targets for these patients.

Nutraceutical strategies for alleviation of UVB phototoxicity.

Ultraviolet B exposure to keratinocytes promotes carcinogenesis by inducing pyrimidine dimer lesions in DNA, suppressing the nucleotide excision repair mechanism required to fix them, inhibiting the apoptosis required for the elimination of initiated cells, and driving cellular proliferation. Certain nutraceuticals - most prominently spirulina, soy isoflavones, long-chain omega-3 fatty acids, the green tea catechin epigallocatechin gallate (EGCG) and Polypodium leucotomos extract - have been shown to oppose photocarcinogenesis, as well as sunburn and photoaging, in UVB-exposed hairless mice. It is proposed that spirulina provides protection in this regard via phycocyanobilin-mediated inhibition of Nox1-dependent NADPH oxidase; that soy isoflavones do so by opposing NF-κB transcriptional activity via oestrogen receptor-beta; that the benefit of eicosapentaenoic acid reflects decreased production of prostaglandin E2; and that EGCG counters UVB-mediated phototoxicity via inhibition of the epidermal growth factor receptor. The prospects for practical nutraceutical down-regulation of photocarcinogenesis, sunburn, and photoaging appear favourable.

Cross-Reactivity between Chemical Antibodies Formed to Serum Proteins and Thyroid Axis Target Sites.

In some instances, when chemicals bind to proteins, they have the potential to induce a conformational change in the macromolecule that may misfold in such a way that makes it similar to the various target sites or act as a neoantigen without conformational change. Cross-reactivity then can occur if epitopes of the protein share surface topology to similar binding sites. Alteration of peptides that share topological equivalence with alternating side chains can lead to the formation of binding surfaces that may mimic the antigenic structure of a variant peptide or protein. We investigated how antibodies made against thyroid target sites may bind to various chemical-albumin compounds where binding of the chemical has induced human serum albumin (HSA) misfolding. We found that specific monoclonal or polyclonal antibodies developed against thyroid-stimulating hormone (TSH) receptor, 5'-deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin (TBG), thyroxine (T4), and triiodothyronine (T3) bound to various chemical HSA compounds. Our study identified a new mechanism through which chemicals bound to circulating serum proteins lead to structural protein misfolding that creates neoantigens, resulting in the development of antibodies that bind to key target proteins of the thyroid axis through protein misfolding. For demonstration of specificity of thyroid antibody binding to various haptenic chemicals bound to HSA, both serial dilution and inhibition studies were performed and proportioned to the dilution. A significant decline in these reactions was observed. This laboratory analysis of immune reactivity between thyroid target sites and chemicals bound to HSA antibodies identifies a new mechanism by which chemicals can disrupt thyroid function.

Correlation between Antibodies to Bacterial Lipopolysaccharides and Barrier Proteins in Sera Positive for ASCA and ANCA.

Individuals with intestinal barrier dysfunction are more prone to autoimmunity. Lipopolysaccharides (LPS) from gut bacteria have been shown to play a role in systemic inflammation, leading to the opening of the gut and blood-brain barrier (BBB). This study aims to measure antibodies against LPS and barrier proteins in samples positive for anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) and compare them with these same antibodies in controls to determine whether a correlation between LPS and barrier proteins could be found. We obtained 94 ASCA- and 94 ANCA-positive blood samples, as well as 188 blood samples from healthy controls. Samples were assessed for antibodies to LPS, zonulin+occludin, S100B, and aquaporin-4 (AQP4). Results show significant elevation in antibodies in about 30% of ASCA- and ANCA-positive sera and demonstrate positive linear relationships between these antibodies. The findings suggest that individuals positive for ASCA and ANCA have increased odds of developing intestinal and BBB permeability compared to healthy subjects. The levels of LPS antibodies in both ASCA- and ANCA-positive and negative specimens showed from low and moderate to high correlation with antibodies to barrier proteins. This study shows that LPS, by damaging the gut and BBBs, contribute to the extra-intestinal manifestation of IBD. We conclude that IBD patients should be screened for LPS antibodies in an effort to detect or prevent possible barrier damage at the earliest stage possible to abrogate disease symptoms in IBS and associated disorders.

Immune reactivity against a variety of mammalian milks and plant-based milk substitutes.

The research reported here seeks to evaluate the allergenicity and antigenicity of different mammalian and plant-based milks/milk substitutes in healthy subjects. We used ELISA to measure IgE and IgG antibodies against cow, goat, sheep, camel, human milks, and soy, almond, and coconut plant-based milk substitutes, as well as IgA antibodies against all these apart from human milk, in 500 individuals in order to find the percentage of antibody elevation. IgG and IgE positivity showed that human milk was the least antigenic and allergenic, followed by camel milk. Cow's milk showed the highest percentage of elevation or reactivity. Among plant-based milk substitutes, the almond-based substitute was the most allergenic with the highest IgE reactivity, while the coconut milk substitute was lowest. For IgG and IgA immuno-reactivity, soy was first, with coconut again the lowest. We found IgE and IgG immune reactivity against coconut, almond and soymilks in some individuals who were non-reactive to mammalian milk, therefore, we should not assume that consumption of these milks is automatically without risk of allergenic response. We selected 24 samples out of the original 500 for the measurement of IgE antibodies against five different types of cow's milk, from non-organic to organic, A1 and A2. Statistical variance analysis detected no significant difference in IgE, IgG and IgA immune reactivities of the five different cow milks. Our results showed that if an individual is immuno-reactive to cow's milk, organic or not, the probability of reacting to goat and sheep milk is very high. Overall, the results presented here showed that for individuals allergic to cow's milk, the least allergenic alternatives in descending order are human, camel, sheep, and goat milks. Before choosing an alternative for cow's milk, one must go through accurate and quantitative blood testing for determination of IgE, IgG and IgA antibodies against different mammalian and plant-based milks/milk substitutes.

Correlation between antibodies to bisphenol A, its target enzyme protein disulfide isomerase and antibodies to neuron-specific antigens.

Evidence continues to increase linking autoimmunity and other complex diseases to the chemicals commonly found in our environment. Bisphenol A (BPA) is a synthetic monomer used widely in many forms, from food containers to toys, medical products and many others. The potential for BPA to participate as a triggering agent for autoimmune diseases is likely due to its known immunological influences. The goal of this research was to determine if immune reactivity to BPA has any correlation with neurological antibodies. BPA binds to a target enzyme called protein disulfide isomerase (PDI). Myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) are neuronal antigens that are target sites for neuroinflammation and neuroautoimmunity. We determined the co-occurrence of anti-MBP and anti-MOG antibodies with antibodies made against BPA bound to human serum albumin in 100 healthy human subjects. Correlation between BPA to PDI, BPA to MOG, BPA to MBP, PDI to MBP and PDI to MOG were all highly statistically significant (P < 0.0001). The outcome of our study suggests that immune reactivity to BPA-human serum albumin and PDI has a high degree of statistical significance with substantial correlation with both MBP and MOG antibody levels. This suggests that BPA may be a trigger for the production of antibodies against PDI, MBP and MOG. Immune reactivity to BPA bound to human tissue proteins may be a contributing factor to neurological autoimmune disorders. Further research is needed to determine the exact relationship of these antibodies with neuroautoimmunities. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd.

The Gut-Brain Axis: Autoimmune and Neuroimmune Disorders.

No Abstract Available.

Elevated levels of antibodies against xenobiotics in a subgroup of healthy subjects.

In spite of numerous research efforts, the exact etiology of autoimmune diseases remains largely unknown. Genetics and environmental factors, including xenobiotics, are believed to be involved in the induction of autoimmune disease. Some environmental chemicals, acting as haptens, can bind to a high-molecular-weight carrier protein such as human serum albumin (HSA), causing the immune system to misidentify self-tissue as an invader and launch an immune response against it, leading to autoimmunity. This study aimed to examine the percentage of blood samples from healthy donors in which chemical agents mounted immune challenges and produced antibodies against HSA-bound chemicals. The levels of specific antibodies against 12 different chemicals bound to HSA were measured by ELISA in serum from 400 blood donors. We found that 10% (IgG) and 17% (IgM) of tested individuals showed significant antibody elevation against aflatoxin-HSA adduct. The percentage of elevation against the other 11 chemicals ranged from 8% to 22% (IgG) and 13% to 18% (IgM). Performance of serial dilution and inhibition of the chemical-antibody reaction by specific antigens but not by non-specific antigens were indicative of the specificity of these antibodies. Although we lack information about chemical exposure in the tested individuals, detection of antibodies against various protein adducts may indicate chronic exposure to these chemical haptens in about 20% of the tested individuals. Currently the pathological significance of these antibodies in human blood is still unclear, and this protein adduct formation could be one of the mechanisms by which environmental chemicals induce autoimmune reactivity in a significant percentage of the population.

The evolution of food immune reactivity testing: why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another.

The gold standard for identifying food reactions is the elimination-provocation diet. Embarking on this long, tedious journey takes an expert practitioner and a completely dedicated patient, with a whole lot of patience from both. In the contemporary fast lane, microwave, "give me a pill" popping, I-want-satisfaction-now society, many clinicians have turned to laboratory assessments for quick answers to food reactivity. From the introduction of cytotoxic testing for food allergies in 1947 until today, food reactivity testing has evolved and branched; it has been both pseudoimproved and scientifically improved. With multiple available options for methodology, specimen types, and clinical lab, how is a clinician expected to find the one that fits the requirements of a particular practice? How, indeed, when one self-promoting paper supports a particular methodology, while another criticizes it? In this article, with the benefit of his years of training and experience as a research scientist and test development expert, the author, who is trained in both microbiology and immunology, discusses the history of food testing, analyzes the criticisms of it, reviews the scientific literature, and tours the methodologies.

Oral tolerance and its relationship to food immunoreactivities.

A child is born with almost no protective immune system other than passive immunity and maternal transfer of immunoglobulin G (IgG) against various food antigens and infectious agents. This lack provides a window of opportunity for infectious attacks in the first 6 mo of life as the infant's body begins to develop its own immune system. As the maternal IgG is catabolized, the child's mucosal immune system evolves its own immunocytes and starts producing a significant amount of immunoglobulin A (IgA) and immunoglobulin M (IgM) against pathogens and food antigens. This antibody production helps modulate or inhibit colonization by bacteria or yeast and to prevent penetration of the mucosal tissue by a variety of dangerous lumenal antigens. Simultaneously, the body develops its own suppressive mechanism or oral tolerance to avoid local and peripheral immune reactivities to microbial and dietary antigens. In this article, the author describes the (1) importance of oral tolerance in maintaining homeostasis against bacterial toxins and food antigens; (2) way in which antigen-presenting cells (APCs), through their collaboration with effector T (TEFF) cells, T-helper (TH) cells, and regulatory T (TREG) cells, regulate the immune system to induce anergy or immune suppression; (3) the importance of various factors in the induction of oral tolerance and the consequences of its breakdown; and (4) the reasons why a disruption of oral tolerance to food antigens and bacterial toxins can result in autoimmunity.

Molecular mimicry as a mechanism for food immune reactivities and autoimmunity.

The mucosal immune system is constantly exposed to challenges from the antigenic substances found in food and released from the body's own microbial flora. The body's normal tolerance to friendly antigenic substances can be disrupted by a number of factors, such as disease, injury, shock, trauma, surgery, drugs, blood transfusion, environmental triggers, etc. When this disruption happens, the ingestion of foods containing antigenic substances that have compositions similar to those of the body's autoantigens can result in the production of antibodies that react not only against the food antigens but also the body's own tissues. This response is known as food autoimmune reactivity. Between 7% and 10% of the world's population suffers from some form of autoimmune disease. Each patient's antibodies, both immunoglobulin A (IgA) + immunoglobulin M (IgM) in the saliva and immunoglobulin G (IgG) and IgA in the blood must be examined to give a complete picture of food immune reactivity. A host of health problems and autoimmune disorders have increasingly become associated with some of the most commonly consumed foods in the world, such as wheat and milk. Many of these problems can be traced to molecular mimicry. The peptide sequences of foods such as milk and wheat are similar to those of human molecules, such as myelin oligodendrocyte glycoprotein, human islet cell tissue, and human aquaporin 4 (AQP4). This similarity can result in cross-reactivity that leads to food autoimmunity and even autoimmune disorders, such as multiple sclerosis (MS), celiac disease (CD), and neuromyelitis optica. Further research is needed to determine what other foods have dangerous sequence similarities to human tissues and what methods are available to test for the autoantibodies resulting from these molecular, mimicry-induced misfires of the immune system. The identification and removal of corresponding food triggers can then be used as the basis of therapy.

Lectins, agglutinins, and their roles in autoimmune reactivities.

Lectins are carbohydrate-binding proteins present throughout nature that act as agglutinins. Approximately 30% of our food contains lectins, some of which may be resistant enough to digestion to enter the circulation. Because of their binding properties, lectins can cause nutrient deficiencies, disrupt digestion, and cause severe intestinal damage when consumed in excess by an individual with dysfunctional enzymes. These effects are followed by disruption of intestinal barrier integrity, which is the gateway to various autoimmunities. Shared amino acid motifs between dietary lectins, exogenous peptides, and various body tissues may lead to cross-reactivity, resulting in the production of antibodies against lectin and bacterial antigens, followed by autoimmunity. The detection of immunoglobulin G (IgG) or immunoglobulin A (IgA) antibodies against specific lectins may serve as a guide for the elimination of these lectins from the diet. It is proposed that this process can reduce the peripheral antigenic stimulus and, thereby, result in a diminution of disease symptoms in some-but not all-patients with autoimmune disorders.

Immune reactivities to peanut proteins, agglutinins, and oleosins.

CONTEXT: Certain individuals are sensitive enough to react to peanuts and peanut oil, sometimes with deadly effect. It is thus crucial to have an accurate testing methodology for the assessment of allergies and immune reactivities to peanuts and their components, such as agglutinins and oleosins. Currently, skin-prick testing is performed only with the water-soluble components of peanut proteins and can produce false negatives. Testing with all possible food antigens and with both immunoglobulin G (IgG) and immunoglobulin E (IgE) antibodies may offer a more accurate alternative. OBJECTIVE: The research team intended to measure IgG and IgE antibodies against peanut proteins, agglutinins, and oleosins to identify variations in IgG and IgE immune reactivities to these antigens among the general population. DESIGN: Sera from 288 healthy individuals-144 males of different ethnicities, aged 18-65 y with a median age of 35.5 y, and 144 females of different ethnicities, aged 18-65 y with a median age of 36.2 y-were obtained from Innovative Research, Inc. Four sera from patients with a known allergy to peanuts and 4 sera from individuals with no known allergy to peanuts were used as positive and negative controls. Several wells in the microtiter plate were coated with unrelated proteins, such as human serum albumin, rabbit serum albumin, and bovine serum albumin and used only for the determination of any background in the enzyme-linked immunosorbent assay (ELISA). SETTING: Immunosciences Lab, Inc, Los Angeles, CA, USA. OUTCOME MEASURES: The sera were screened for peanut-specific IgG and IgE antibodies against water-soluble proteins of peanut, peanut agglutinins, and peanut oleosins, using the ELISA. Color development was measured at 405 nM. For demonstration of the specificity of the antibodies, inhibition ELISA was performed with 4 sera that had very high levels of IgG and IgE antibodies. RESULTS: Using mean values as the cutoff, 19%, 17%, and 22% of the specimens tested for IgG antibodies and 14%, 11%, and 14% of the specimens tested for IgE antibodies produced high levels of antibodies against peanut proteins, agglutinins, and oleosins, respectively. CONCLUSIONS: The study's findings support the proposition that IgE sensitization to foods may not necessarily coincide with positive prick tests to commercial extracts. Falsely negative skin testing or IgG, IgA, or IgE antibody testing is often linked to the nature of the preparation of the food antigens and their use in in-vivo and in-vitro testing. The study's results support the need to improve the quality of food extracts used in the diagnosis of allergies and immune reactivity to nuts and seeds. Testing should use all possible food antigens and measure both IgG and IgE antibodies.

Immune reactivity to food coloring.

Artificial food dyes are made from petroleum and have been approved by the US Food and Drug Administration (FDA) for the enhancement of the color of processed foods. They are widely used in the food and pharmaceutical industries to increase the appeal and acceptability of their products. Synthetic food colorants can achieve hues not possible for natural colorants and are cheaper, more easily available, and last longer. However, since the use of artificial food coloring has become widespread, many allergic and other immune reactive disorders have increasingly been reported. During the past 50 y, the amount of synthetic dye used in foods has increased by 500%. Simultaneously, an alarming rise has occurred in behavioral problems in children, such as aggression, attention deficit disorder (ADD), and attention-deficit/hyperactivity disorder (ADHD). The ingestion of food delivers the greatest foreign antigenic load that challenges the immune system. Artificial colors can also be absorbed via the skin through cosmetic and pharmaceutical products. The molecules of synthetic colorants are small, and the immune system finds it difficult to defend the body against them. They can also bond to food or body proteins and, thus, are able to act in stealth mode to circumvent and disrupt the immune system. The consumption of synthetic food colors, and their ability to bind with body proteins, can have significant immunological consequences. This consumption can activate the inflammatory cascade, can result in the induction of intestinal permeability to large antigenic molecules, and could lead to cross-reactivities, autoimmunities, and even neurobehavioral disorders. The Centers for Disease Control (CDC) recently found a 41% increase in diagnoses of ADHD in boys of high-school age during the past decade. More shocking is the legal amount of artificial colorants allowed by the FDA in the foods, drugs, and cosmetics that we consume and use every day. The consuming public is largely unaware of the perilous truth behind the deceptive allure of artificial color.

Immune reactivities against gums.

CONTEXT: Different kinds of gums from various sources enjoy an extremely broad range of commercial and industrial use, from food and pharmaceuticals to printing and adhesives. Although generally recognized as safe by the US Food and Drug Administration (FDA), gums have a history of association with sensitive or allergic reactions. In addition, studies have shown that gums have a structural, molecular similarity to a number of common foods. A possibility exists for cross-reactivity. OBJECTIVE: Due to the widespread use of gums in almost every aspect of modern life, the overall goal of the current investigation was to determine the degree of immune reactivity to various gum antigens in the sera of individuals representing the general population. DESIGN: The study was a randomized, controlled trial. PARTICIPANTS: 288 sera purchased from a commercial source. OUTCOME MEASURES: The sera was screened for immunoglobulin G (IgG) and immunoglobulin E (IgE) antibodies against extracts of mastic gum, carrageenan, xantham gum, guar gum, gum tragacanth, locust bean gum, and ß-glucan, using indirect enzyme-linked immunosorbent assay (ELISA) testing. For each gum antigen, inhibition testing was performed on the 4 sera that showed the highest IgG and IgE immune reactivity against the different gums used in the study. Inhibition testing on these same sera for sesame albumin, lentil, corn, rice, pineapple, peanut, pea protein, shrimp, or kidney bean was used to determine the cross-reactivity of these foods with the gum. RESULTS: Of the 288 samples, 4.2%-27% of the specimens showed a significant elevation in IgG antibodies against various gums. Only 4 of 288, or 1.4%, showed a simultaneous elevation of the IgG antibody against all 7 gum extracts. For the IgE antibody, 15.6%-29.1% of the specimens showed an elevation against the various gums. A significant percentage of the specimens, 12.8%, simultaneously produced IgE antibodies against all 7 tested extracts. CONCLUSIONS: Overall, the percentage of elevation in IgE antibodies against different gum extracts, with the exception of carrageenan, was much higher than for the IgG antibody. The results of the current study showed that a subgroup of healthy individuals who produced not only IgG but also IgE antibodies against various gums may suffer from hidden food immune reactivities and sensitivities. Further study is needed to examine the clinical importance of gums and cross-reactive food antibodies in symptomatic individuals.

The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health.

Gut luminal dysbiosis and pathobiosis result in compositional and biodiversified alterations in the microbial and host co-metabolites. The primary mechanism of bacterial evolution is horizontal gene transfer (HGT), and the acquisition of new traits can be achieved through the exchange of mobile genetic elements (MGEs). Introducing genetically engineered microbes (GEMs) might break the harmonized balance in the intestinal compartment. The present objectives are: 1. To reveal the role played by the GEMs' horizontal gene transfers in changing the landscape of the enteric microbiome eubiosis 2. To expand on the potential detrimental effects of those changes on the human genome and health. A search of articles published in PubMed/MEDLINE, EMBASE, and Scielo from 2000 to August 2023 using appropriate MeSH entry terms was performed. The GEMs' horizontal gene exchanges might induce multiple human diseases. The new GEMs can change the long-term natural evolution of the enteric pro- or eukaryotic cell inhabitants. The worldwide regulatory authority's safety control of GEMs is not enough to protect public health. Viability, biocontainment, and many other aspects are only partially controlled and harmful consequences for public health should be avoided. It is important to remember that prevention is the most cost-effective strategy and primum non nocere should be the focus.