Alopecia areata and the gut—the link opens up for novel therapeutic interventions

ABSTRACT

Introduction: This review aims to raise the potential of the modern society’s impact on gut integrity often leading to increased intestinal permeability, as a cause or driver of Alopecia Areata (AA) in genetically susceptible people. With the increasing rate of T cell-driven autoimmunity, we hypothesize that there is a common root cause of these diseases that originates from chronic inflammation, and that the gut is the most commonly exposed area with our modern lifestyle.

Areas covered: We will discuss the complexity in the induction of AA and its potential link to increased intestinal permeability. Our main focus will be on the gut microbiome and mechanisms involved in the interplay with the immune system that may lead to local and/or peripheral inflammation and finally, tissue destruction.

Expert opinion: We have seen a link between AA and a dysfunctional gastrointestinal system which raised the hypothesis that an underlying intestinal inflammation drives the priming and dysregulation of immune cells that lead to hair follicle destruction. While it is still important to resolve local inflammation and restore the IP around the hair follicles, we believe that the root cause needs to be eradicated by long-term interventions to extinguish the fire driving the disease.

KEYWORDS:

• Alopecia areata
• intestinal permeability
• chronic inflammation
• autoimmunity

Article highlights

• Chronic inflammation as an underlying driver of AA has not previously been discussed. We have seen a link between disease manifestation and IBS-like symptoms, indicating that inflammation in the gut—causing a leaky epithelium and increased stress on the immune system—may be a driver of AA as well as in other autoimmune conditions where this is more commonly described.

• The gut microbiota is important in the function of the immune system and also for oral tolerance, which is of importance particularly in genetically susceptible people. Having a balanced microbiome is thus essential for a tight epithelial barrier and a functional and regulatory immune system.

• Modern society with its processed Western diet has greatly impacted on global health and dramatically increased allergies and autoimmune diseases.

• A high intake of fibers affects the make up of the intestinal microbiota, primarily increasing short-chain fatty acid concentrations that have beneficial immunomodulatory effects (eg increasing Treg numbers and function).

• Several concomitant triggers are needed to induce AA, however, an underlying chronic inflammation and its effect on the immune system may undermine its regulatory function which then permits the maintenance of the ongoing tissue destruction.

• We believe that adressing the root cause and driver of disease is essential for a successful outcome. Thus, we recommend future therapies and interventions in AA to start with eradication of any ongoing inflammation—today commonly located in the gut—before also dealing with the local attack on the hair follicles.

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Acknowledgement

We would like to acknowledge Jayne Waddell, founder of the alopecia for research foundation AAR-UK, that is the originator of the link between the gut and alopecia areata. In her many interactions with patients she noticed that most of them had IBS-like problems whereas the triggers that induced their disease were different. She founded AAR-UK in order to support research of the intestinal contribution to driving this devastating disease.

Declaration of interest

The authors are both employed by AstraZeneca (Respiratory, Inflammation and Autoimmunity IMED Biotech unit). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.