Epithelial barrier dysfunction and associated diseases in companion animals: Differences and similarities between humans and animals and research needsSince the 1960s, more than 350,000 new chemicals have been introduced into the lives of humans and domestic animals. Many of them have become part of modern life and some are affecting nature as pollutants. Yet, our comprehension of their potential health risks for both humans and animals remains partial. The “epithelial barrier theory” suggests that genetic predisposition and exposure to diverse factors damaging the epithelial barriers contribute to the emergence of allergic and autoimmune conditions. Impaired epithelial barriers, microbial dysbiosis, and tissue inflammation have been observed in a high number of mucosal inflammatory, autoimmune and neuropsychiatric diseases, many of which showed increased prevalence in the last decades. Pets, especially cats and dogs, share living spaces with humans and are exposed to household cleaners, personal care products, air pollutants, and microplastics. The utilisation of cosmetic products and food additives for pets is on the rise, unfortunately, accompanied by less rigorous safety regulations than those governing human products. In this review, we explore the implications of disruptions in epithelial barriers on the well-being of companion animals, drawing comparisons with humans, and endeavour to elucidate the spectrum of diseases that afflict them. In addition, future research areas with the interconnectedness of human, animal, and environmental well-being are highlighted in line with the “One Health” concept. many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation. Sun N, Ogulur I, Mitamura Y, et al. The epithelial barrier theory and its associated diseases. Allergy. 2024; 00: 1–46. Read the article here.
The epithelial barrier theory and its associated diseasesThe prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation. Sun N, Ogulur I, Mitamura Y, et al. The epithelial barrier theory and its associated diseases. Allergy. 2024; 00: 1–46. Read the article here.
Advanced Human Models For Environmental Toxic Substances Replacing Mouse Research SummaryThe advancement of human in vivo-like cellular systems utilizes induced pluripotent stem cell-derived organoids and organ-on-a-chip technology as substitutes for mouse models in studying the effects of environmental exposure to toxic substances.More than 350,000 chemical substances have been introduced into our environment, coinciding with a noticeable increase in autoimmune and allergic diseases, reaching epidemic proportions since 1960s.Exposure to chemicals disrupts cellular processes, initiating inflammatory responses and cellular demise, which can culminate in organ damage and potentially exacerbate the development of chronic diseases. Therefore, it is imperative to thoroughly assess the toxicity of these substances to safeguard public health and mitigate the risks associated with their presence in our environment.Human research has been limited and remains impractical due to the known toxicity of certain substances. Consequently, there is a pressing need to shift focus towards methodologies aligned with the principles of Replacement, Reduction, and Refinement (the 3Rs) in animal research. This approach advocates for the replacement of animal models wherever feasible, prioritizing alternative methods to analyze both dosage effects and the molecular mechanisms of toxicity in these substances. Moreover, there is a critical imperative to advance the development of in vivo-like human models, which can more accurately simulate human physiology and responses to chemical exposure. By embracing these principles and advancing innovative research techniques, we can enhance our understanding of toxicity while minimizing reliance on animal testing and advancing human-relevant research methodologies.We created experimental models that mimic human in vivo conditions by integrating induced pluripotent stem cell (iPSC)-derived intestine organoids with organ-on-a-chip technology. This approach enabled us to illustrate how epithelial cells respond to environmental toxins, demonstrating both their activation and regulatory mechanisms.We elucidated the molecular mechanisms by which these substances impact intestinal epithelial cells, employing a combination of transcriptomic and proteomic analyses, alongside deletion studies utilizing CRISPR/Cas9 and siRNA technologies. Through these methods, we have gained insights that enable us to inform strategies aimed at mitigating associated diseases, regulating substance dosages, formulating less harmful products, and investigating novel therapeutic interventions. Our newly established epithelial laboratory and innovative in vivo-relevant methodology are in accordance with the principles of the 3Rs, offering a significant decrease in reliance to animal research.
Epithelial Barrier Theory & Global Health Crisis
Epithelial Barrier Theory & Global Health Crisiselucidated the molecular mechanisms by which these substances impact intestinal epithelial cells, e
