Expert Q&A: Atopic Dermatitis and the Role of Microbial Modulation

Atopic dermatitis (AD) is a common inflammatory skin disease affecting between 10% and 20% of children.^1,2 In 95% of cases, it develops within the first 5 years of life2 and is characterized by a mild, relapsing course.³

AD is a multifactorial disease — its development is influenced by a host of hereditary, environmental, immunological, pharmacological, psychological, and nutritional factors.⁴ Over the past decade, research efforts have been aimed at identifying the effects of nutritional interventions with probiotics on the management and progression of AD. Several studies in particular have suggested the beneficial role of probiotic supplementation in children with AD,^5-7 sparking further interest in the potential therapeutic use of probiotics. 

In an interview with Dermatology Advisor, Paul V. Licciardi, PhD, research fellow at the Murdoch Childrens Research Institute and principal fellow at The University of Melbourne, Australia, and Johan Garssen, PhD, head of the pision of pharmacology at Utrecht University, The Netherlands, discussed the latest insights about the effects of probiotic supplementation and microbial modulation on the management of AD.

Dermatology Advisor: How does early intestinal microbial colonization influence the onset and course of AD and other allergic disease in children?

Paul V. Licciardi, PhD: There is now substantial evidence that suggests the composition and persity of microbial colonization of the intestinal tract during early life can dictate whether an inpidual develops AD or other allergic diseases later in life.8 This is particularly true in high-risk inpiduals (ie, one or both parents having an allergic disease) who have a greater susceptibility to developing allergic disease. We know that microbial colonization with the right kind of bacteria provides critical signals to the developing immune system so that it learns not to react in response to otherwise harmless substances such as foods or other antigens.

Dermatology Advisor: Is there a difference in the microbiome composition of children with AD and children who are AD-free?

Dr Licciardi: Yes, many studies have shown that children with AD have different gut microbiota profiles than healthy children. Beneficial bacteria such as Bacteroides are reduced in the microbiome of children with AD while pathogenic bacteria such as Clostridia are enriched. The development of new technologies has enabled a much more extensive examination of microbial profiles in patients with AD than previously possible.

Dermatology Advisor: How does the combined administration of prenatal and postnatal probiotics influence the composition of the infant gut microbiome and, in particular, the susceptibility to AD in early childhood? Is prenatal supplementation as equally effective as postnatal supplementation?

Dr Licciardi: The use of probiotics to prevent the development of AD (and other allergic diseases) has been the subject of intense scientific debate over the past 20 years. Probiotics are defined by the World Health Organization (WHO) as live microorganisms that when administered in adequate amounts confer a health benefit to the host. The rationale for probiotic use is that early life supplementation may be able to restore the gut microbiota profile and shape the immune system towards a healthier phenotype, thereby preventing AD and other allergic diseases. The data to date suggest that combined prenatal/postnatal supplementation may be the most effective strategy while postnatal supplementation alone has limited benefit.9 However, differences between the many different clinical studies undertaken to date as well as the variety of probiotics available adds further complexity to this issue.

Dermatology Advisor: Which factors influence the ability of microorganisms to modulate the immune response and protect against the development of allergic disease?

Dr Licciardi: Under normal conditions, the microbiome can protect against the development of allergic disease by several mechanisms. Microbial species in the intestines can maintain epithelial barrier integrity and function, which helps prevent sensitization to particular allergens. Microorganisms in the intestines are also able to interact with specific immune cells such as dendritic cells and T-lymphocytes to produce cytokines and other regulatory molecules that protect against allergic responses. Production of microbial metabolites such as short-chain fatty acids following the fermentation of dietary fiber also have important effects on promoting anti-inflammatory responses, which help prevent the development of allergic diseases.

Dermatology Advisor: How much published clinical evidence supports the positive effects of microbial modulation on AD?

Johan Garssen, PhD: Several published studies point to the effects of microbiome modulation on atopic dermatitis.^10,11 However, it is difficult to compare the results from these studies due to different intervention scenarios, dosages, and pro- and/or prebiotics used. Scientists/companies need to realize that the effects are highly dependent on the type of strain and also on the dosage, intervention regime, etc. Nevertheless, the impact of microbiome modulation on AD is one of the new ideas/concepts requiring attention and understanding.   

Dermatology Advisor: Which knowledge gaps still need to be filled about the potentially beneficial role of probiotics in patients with AD?

Dr Garssen: The awareness is growing that microbiome modulation might be a key new intervention strategy. But we need more clinical studies and mechanistic preclinical studies in order to validate and understand the clinical benefits of probiotics. It is important to realize that just 10 years ago microbiome modulation, as a tool to influence immune reactions/allergies/inflammation, was viewed as alternative medicine and with a lot of skepticism. The skepticism is disappearing now. Today, top scientists — award winners — realize and understand the relevance of our microbiome in health and disease. As scientists, we have to accept that more time is needed to understand, select, and decide on the best way to modulate our microbiome safely and effectively.  

References

1. Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387:1109-1122.
2. Wollina U. Microbiome in atopic dermatitis. Clin Cosmet Investig Dermatol. 2017;10:51-56.
3. Ballardini N, Kull I, Soderhall C, et al. Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: A report from the BAMSE birth cohort. Br J Dermatol. 2013;168:588-594.
4. Hulshof L, van’t Land B, Sprikkelman AB, et al. Role of microbial modulation in management of atopic dermatitis in children. Nutrients. 2017;9(8):E854.
5. Miraglia del Guidice M Jr, de Luca MG, Capristo C. Probiotics and atopic dermatitis. A new strategy in atopic dermatitis. Dig Liver Dis. 2002;34:S68-S71.
6. Pessi T, Sutäs Y, Hurme M, et al. Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy. 2000;30:1804-1808.
7. Wang IJ, Wang JY. Children with atopic dermatitis show clinical improvement after Lactobacillus exposure. Clin Exp Allergy. 2015;45(4):779-787.
8. Reynolds LA, Finlay BB. Early life factors that affect allergy development. Nat Rev Immunol. 2017;17(8):518-528.
9. Ismail IH, Licciardi PV, Tang ML, et al. Probiotic effects in allergic disease. J Paediatr Child Health. 2013;49(9):709-715. 
10. Lin Rj, Qui LH, Guan RZ, et al. Protective effect of probiotics in the treatment of infantile eczema. Exp Ther Med. 2015;9(5):1593-1596. 
11. Notay M, Foolad N, Vaughn AR, et al. Probiotics, prebiotics, and synbiotics for the treatment and prevention of adult dermatological diseases [published online July 5, 2017]. Am J Clin Dermatol. doi:10.1007/s40257-017-0300-2