Aaron Lerner

Microbial transglutaminase (mTG) is a food-processing enzyme widely used for protein cross-linking in processed foods. Experimental, serological, and disease-specific studies suggest that mTG and mTG-modified protein complexes may possess immunogenic and pro-inflammatory properties, particularly in the context of celiac disease. Through transamidation and cross-linking, mTG can generate post-translationally modified protein complexes and neo-epitopes that may interact with host immune pathways. This review critically evaluates the available evidence relevant to mTG within the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) framework. The evidence is strongest for dietary exposure and mTG-associated immunogenicity, whereas evidence for mTG-specific clinical manifestations, improvement after selective withdrawal, systemic autoimmunity, and causal ASIA induction remains limited or indirect. Accordingly, mTG should currently be considered a candidate nutritional/environmental adjuvant rather than a clinically validated ASIA-inducing factor. These observations warrant further independent investigation of human exposure, gastrointestinal biological activity, dose-response relationships, susceptible populations, immunological biomarkers, and long-term safety.

Advances in affordable genetic engineering have accelerated the creation and large-scale environmental release of genetically modified microorganisms (GMMs). While beneficial applications exist, GMMs may present unique, long-term risks to human and environmental health. Unlike static chemicals, GMMs are biologically active, self-replicating entities capable of rapid mutation and global dispersal. Current regulatory frameworks place responsibility on each country to regulate GMMs, without a clear, coordinated international policy. This review details critical risk scenarios, including horizontal gene transfer to native species and the possible disruption of vital human microbiomes (gut, oral, and infant), which could increase resistance to degradation, promote traits that expand a microbe’s range of hosts or ecological niches, and enhance the production of novel metabolites with unexpected biological activity. In soil, GMMs may support the emergence of “super bugs” or destabilize carbon sequestration cycles, potentially impacting climate resilience. Engineered microbial enzymes in the food supply may also act as environmental drivers of autoimmunity. Given the limited understanding of microbial ecology, we propose a decision-based biosafety workflow emphasizing pre-release risk assessment and continuous post-release monitoring. We urge national and international regulators to adopt the precautionary principle to better protect human health and the environment from the potential negative outcomes of GMMs.

The incidence of autoimmune diseases is on the rise, and multiple pathophysiological mechanisms may contribute to this trend. These include sequence similarity, cross reactive antibodies, molecular mimicry, dysbiosis, post-translational modification of processed nutrients, and luminal horizontal gene transfer. Recently, environmental adjuvants have been suggested to play an active role in auto-immunogenesis, collectively referred to as the ASIA syndrome (autoimmune/inflammatory syndrome induced by adjuvants). The present narrative review provides a comprehensive overview of gluten, a widely consumed food additive, known for its pro-inflammatory and immunogenic properties. Gluten is implicated in several autoimmune conditions and meets both the major and minor diagnostic criteria for ASIA syndrome as an adjuvant. It is hoped that this present review will stimulate furthermore research on gluten, aiming to mitigate its risky aspects for public health.

It is now known that diet or food is one of the environmental factors that can induce or contribute to autoimmunity. In a healthy person with a normal functioning immune system, food substances encounter no resistance and are allowed passage through the immune barriers without triggering immune reactivity. However, clinicians are becoming increasingly aware that modern food-processing methods can increase or decrease the immune reactivity of foods, including allergic reactions. Immune reactions to undigested food antigens could result in the production of IgE antibodies, which are involved in immediate immune reactivity, and in IgG and IgA antibodies, which are involved in delayed immune reactivity. Currently, measurements of these antibodies are generally only performed against antigens derived from raw foods. However, testing for food reactivity based only on raw food consumption is inaccurate because people eat both raw and cooked foods. Even home-cooked foods undergo different kinds of preparation or processing. Food processing can change the structure of raw food materials into secondary, tertiary, and quaternary structures that can have different reactive properties. This can affect the body’s normal oral tolerance of food, causing the immune system to mistakenly identify food as a harmful foreign substance and react to it immunologically, leading to food immune reactivity. This abnormal reaction to food molecules can lead to the production of antibodies against not just target food antigens but also the body’s own tissues, which can have significant implications in autoimmunity induction due to cross-reactivity and the other mechanisms discussed here. We hope that this present review will stimulate further research on the role of modified food antigens in the induction of autoimmunity based on some or all of the key points discussed in this review.

Magnesium is an essential mineral for the human body, and its deficiency causes multiple detrimental cellular and organ dysfunctions. The issue of its routine supplementation is debatable, but there is no doubt that in case of depletion, it should be supplemented. Because of its role in inflammatory and autoimmune conditions, its serum levels have been frequently analyzed. However, its role in rheumatological diseases has been barely investigated. The present review aims to screen the literature for well-designed studies in which magnesium was supplemented to cure rheumatological conditions. SciELO, PubMed, and Web of Science databases were screened between 1966 and April 2024 for the literature on this topic. Only one study fulfilled the inclusion criteria and demonstrated that 300 mg/day of oral magnesium reduced insulin resistance in rheumatoid arthritis patients. The lack of studies on this subject shows that additional studies are required to understand the causal relationship between magnesium supplementation and disease treatment.

To systematically review the literature for cases using homeopathy in which complete healing was observed. Scielo, Pubmed, CINAHL, and Embase databases were systematically screened for case reports and series of patients successfully cured by homeopathy between 1966 and August 2022. Language limitation was not used. Forty-nine articles, comprising 191 patients, were depicted. Most of them had dermatological conditions (12 papers, 71 patients), followed by infectious (7 papers, 31 patients), neuropsychiatric (10 publications, 11 patients), vascular and hematological (6 manuscripts, 6 patients), and miscellaneous (11 papers, 52 patients) categories. All of them reported cases that were cured of the clinical condition. This article summarizes the case reports in which homeopathy was used and shows the healing of the different treated diseases.

Microbial transglutaminase (mTG) is a frequently consumed processed food additive, and use of its cross-linked complexes is expanding rapidly. It was designated as a processing aid and was granted the generally recognized as safe (GRAS) classification decades ago, thus avoiding thorough assessment according to current criteria of toxicity and public health safety. In contrast to the manufacturer's declarations and claims, mTG and/or its transamidated complexes are proinflammatory, immunogenic, allergenic, pathogenic, and potentially toxic, hence raising concerns for public health. Being a member of the transglutaminase family and functionally imitating the tissue transglutaminase, mTG was recently identified as a potential inducer of celiac disease. Microbial transglutaminase and its docked complexes have numerous detrimental effects. Those harmful aspects are denied by the manufacturers, who claim the enzyme is deactivated when heated or by gastric acidity, and that its covalently linked isopeptide bonds are safe. The present narrative review describes the potential side effects of mTG, highlighting its thermostability and activity over a broad pH range, thus, challenging the manufacturers' and distributers' safety claims. The national food regulatory authorities and the scientific community are urged to reevaluate mTG's GRAS status, prioritizing public health protection against the possible risks associated with this enzyme and its health-damaging consequences.

Gluten has multiple harmful effects that compromise human health, not only in gluten-dependent diseases but also in non-gluten-affected chronic inflammatory conditions. After consumption, the indigestible gluten peptides are modified by luminal microbial transglutaminase or transported through the gut epithelium to interact with the highly populated mucosal immune cells. As a disruptor of gut permeability, gluten peptides compromise tight junction integrity, allowing foreign immunogenic molecules to reach internal compartments. Gliadin peptides are distributed systemically to remote organs, where they encounter endogenous tissue transglutaminase. Following post-translational deamidation or transamidation, the peptides become immunogenic and pro-inflammatory, inducing organ dysfunction and pathology. Cross-reactivity and sequence homology between gluten/gliadin peptides and human epitopes may contribute to molecular mimicry in autoimmunity induction. A gluten-free diet can prevent these phenomena through various mechanisms. As proof of concept, gluten withdrawal alleviates disease activity in chronic inflammatory, metabolic, and autoimmune conditions, and even in neurodegeneration. We recommend combining the gluten-free and Mediterranean diets to leverage the advantages of both. Before recommending gluten withdrawal for non-gluten-dependent conditions, patients should be asked about gut symptomatology and screened for celiac-associated antibodies. The current list of gluten-induced diseases includes celiac disease, dermatitis herpetiformis, gluten ataxia, gluten allergy, and non-celiac gluten sensitivity. In view of gluten being a universal pro-inflammatory molecule, other non-celiac autoinflammatory and neurodegenerative conditions should be investigated for potential gluten avoidance.

Background: Globally, approximately 1.4% of people have celiac disease (CD), induced by gluten sensitivity. If left untreated, it causes small intestinal inflammation and villous atrophy, which can result in failure to thrive, anemia, osteoporosis, malabsorption, and even malignancy. The only treatment option available is a gluten-free diet (GFD). Few studies have looked at the role and perception of telehealth in relation to CD and selective nutrition both before and after the COVID-19 pandemic. Aim: Our goal was to screen and investigate the research conducted both before and after the COVID-19 pandemic concerning the utilization of telehealth applications and solutions in CD and other GFD-dependent circumstances. Methods: We employed a narrative review approach to explore articles that were published in scholarly journals or organizations between the years 2000 and 2024. Only English-language publications were included. PubMed and Google Scholar searches were mainly conducted using the following keywords: telemedicine, telehealth, telecare, eHealth, m-health, COVID-19, SARS-CoV-2, celiac disease, and gluten-free diet (GFD). Manual searches of the references in the acquired literature were also carried out, along with the authors’ own personal contributions of their knowledge and proficiency in this field. Results: Only a few studies conducted prior to the COVID-19 outbreak examined the viewpoints and experiences of adult patients with CD with relation to in-person clinic visits, as well as other options such as telehealth. The majority of patients believed that phone consultations were appropriate and beneficial. Video conferencing and telemedicine became more popular during the COVID-19 pandemic, demonstrating the effectiveness of using these technologies for CD on a global basis. In recent years, urine assays for gluten identification have become accessible for use at home. These tests could be helpful for CD monitoring with telemedicine assistance. Conclusions: The extended knowledge gathered from the COVID-19 pandemic is expected to complement pre-COVID-19 data supporting the usefulness of telemedicine even after the emergent pandemic, encouraging its wider adoption in standard clinical practice. The monitoring and follow-up of CD patients and other GFD-dependent conditions can greatly benefit from telemedicine.