Journal Club: Does the Epithelial Barrier Hypothesis Explain the Increase In Allergy, Autoimmunity, and Other Chronic Conditions?

In the article entitled, “Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity, and other chronic conditions?”, the author conveys that since the 1960s, there has been a steep increase in the prevalence of allergic, autoimmune, and metabolic diseases. This includes the noticeable rise in as asthma and atopic dermatitis (AD). More recently, researchers have also noted an increased number of food allergies and drug-induced allergic reactions. Many have struggled to attribute this increase in prevalence to genetic predisposition, urbanization and modernization, as well as the increased use of antibiotics. Various hypotheses have been proposed for potential causes for this rise, including the hygiene and epithelial barrier hypotheses. The main focus here, however, is the proposed ‘barrier hypothesis’ in connection with the increased prevalence in various allergic afflictions.

The epithelial barrier and its function are the chief characters in the barrier hypothesis. The skin is of course an important barrier to the world, but it is not the only one. If we trace the skin around the lips, we enter the gastrointestinal (GI) tract with its associated epithelial barrier. Similarly, if we trace the skin around a nostril, we enter the respiratory tract with its epithelia. All of these barriers are important in regulating the passage of allergens, irritants, and pathogens from outside the body to inside the body. The barriers also play a key role in controlling the balance of tissue damage and repair signals, limiting tissue injury and working towards mediating inflammation that may occur during tissue repair. When an epithelial barrier becomes disrupted, a series of pathologic events occur, leaving the host susceptible to various disease conditions, such as irritable bowel disease, Type I and Type II diabetes, rheumatoid arthritis, and multiple sclerosis. In fact, damage to the barrier has even been implicated in many neurodegenerative and psychiatric conditions, including Alzheimer disease and autism spectrum disorder. This correlation has led researchers to delve into and explore the various sources behind epithelial barrier damage. Studies have connected various allergens, pathogens, and environmental toxins to damaged barriers. In fact, detergents used in laundry, dishwashing, and household cleaning products have been determined to have a direct toxic effect on epithelial cells, cells that play a large part in maintaining homeostasis.

In addition to the barrier hypothesis, researchers have proposed additional hypotheses for the ongoing rise in diseases, including the hygiene hypothesis. The hygiene hypothesis proposes that certain microorganisms protect against inflammatory diseases and that their loss—due to modern cleansing—results in an increase in allergy, asthma, and autoimmunity. The article proposes that the hygiene hypothesis does not fully explain the increase in prevalence of allergic and autoimmune diseases. For example, water sanitation was launched during the 1920s. However, the allergy and asthma epidemics did not commence until the 1960s. In addition, studies of migrants from developing countries showed a rapid increase in asthma and allergic diseases after moving to the US.

With regards to the barrier hypothesis, the article underscores the prominence of epithelial damage in connection with many different diseases. It discusses how the barrier hypothesis warrants further studies on safe levels of exposure to different chemicals, such as inhaled and ingested detergents, the ingestion of processed foods containing emulsifiers, and microplastics—substances that have been observed to directly cause epithelial barrier damage. The article suggests possible strategies in reducing diseases associated with a disrupted epithelial barrier, including a need for the avoidance of environmental triggers, the development of safer, less-toxic products, and the expansion of novel therapeutic approaches for strengthening the epithelial barrier. With the implementation of these changes, there is the potential to see a shift in the prevalence of allergic, autoimmune, and metabolic diseases.

As clinicians in the midst of this allergic epidemic, this relatively novel thinking suggests that a powerful paradigm shift is brewing. For the first time we may have some real, satisfying answers to the questions our patients ask, especially: “why is this happening to me?”

Disclosures: Dr. Lio and Dominique Butler report no relevant financial disclosures.

Source: Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021 Nov;21(11):739-51.