Skin microbiome-based approach for atopic dermatitis shows potential, but more research needed to ascertain long-term results – A*STAR-funded study

AD is a chronic inflammatory skin condition characterised by disrupted skin barrier function and immune dysregulation. Its onset is typically in early life and is more common in children, afflicting up to 25%.

Children with AD often experience comorbidities such as food allergies, allergic rhinitis, asthma, autoimmune disorders, and recurrent skin infections.

A review funded by Singapore’s Agency for Science, Technology and Research (A*STAR) sought to explore the skin microbiome’s role in paediatric AD and food allergy, and its potential in preventing and treating these conditions.
The researchers searched and reviewed papers published on PubMed, Cochrane Library, and Medline between January 2012 and December 2022.
One of the key findings was that the skin microbiome composition changes dramatically across the AD flare cycle, with microbial diversity dropping as disease severity increases and a concomitant increase in abundance of Staphylococcus aureus ​(S. aureus​) in majority of cases.

S. aureus​ has long been associated with AD and demonstrated its pathogenic effects through various mechanisms, such as disruption of barrier integrity, intrinsic host immune dysregulation, and expression of virulence genes. 

Predominant S. aureus ​strains are often observed in the flare state, while heterogenous Staphylococcus epidermidis​ (S. epidermidis​) strain communities are seen in both flare and post-flare states.  

The predominance of S. aureus​ strains in flares and relative reduction of commensal microbes are linked to skin barrier disruption and inflammation in AD skin.

A meta-analysis reported that about 70% of individuals across all ages with AD are colonised with S. aureus​ on lesional skin, 30% to 40% in non-lesional skin, and 62% in the nares (nostrils).

“AD patients have significantly higher odds of S. aureus colonisation than healthy controls at all sites compared. There is a need for greater understanding of the initiators and drivers of the altered skin microbiome and why S. aureus predominates on AD skin,” ​the researchers wrote.

On non-flare AD skin, microbial diversity remains high, but the composition and functional potential of the microbiome are distinct from healthy individuals. This suggests possible microbiome-related factors that increase the susceptibility to flares.

Additionally, the altered microbiome signature in non-flare AS skin is more pronounced in individuals with high levels of circulating immunoglobulin E (IgE) and associated with molecular changes in the skin surface microenvironmental niche.

“There is growing evidence that commensal microbes may play a mechanistic role in skin barrier repair and attenuate inflammation during AD via aryl hydrocarbon receptor (AhR)-dependent signalling and glucocorticoid-related pathways.​

“In contrast to broad-spectrum antibiotic therapies, repurposing commensal and symbiotic microbes for therapeutic strategies could allow more targeted effects against pathogenic microbes without unintended collateral impact on the rest of the healthy microbiota.” ​

Skin microbiome-based strategies​

There are myriad microbiome studies that have investigated the mechanisms by which AD skin could benefit from a microbial-driven anti-inflammatory approach.

A Methicillin-resistant Staphylococcus aureus (MRSA) skin infection murine study indicated that the Coagulase-negative staphylococci (CoNS) species could contribute to activating other microbes, and interacting with the epidermis to maintain homeostasis and interact or compete with S. aureus​.

S. epidermidis​ is a CoNS that has shown to reduce skin inflammation by regulating toll-like receptor (TLR) pathways, and can produce sphingomyelinase to aid in the production of ceramides to maintain the skin barrier.

These functions suggest the crucial role S. epidermidis​ has on the skin and the potential that could be harnessed for AD treatment.

However, the use of S. epidermidis​ without attenuation would be complex and potentially controversial due to its “dual roles” — protection from pathogens, and stimulating inflammation or causing systemic infections in certain situations.

“Numerous studies have reported that the skin microbiome is closely associated with AD flares, severity, and response to various treatment modalities. But AD is a multifactorial disease affected by genetics, immunology, and environmental influences, thus skin microbiota is not the sole factor. ​

“Harnessing skin microbes as AD biotherapeutics is an emerging field, but more work is needed to investigate whether this approach can lead to sustained clinical responses.​ Several gaps in the existing literature remain to be filled.” ​

The researchers added that many studies demonstrated differences in skin microbiota composition in patients and controls at a single time point, which limits the ability to draw conclusions about causality and temporal progression.

Furthermore, most studies focused on bacterial species alone, and did not explore other microbes, such as viruses and fungi, or their interactions with bacteria and the host.

“Several interventional trials involving children with AD that are under way focus mainly on monitoring skin microbiota changes in response to treatment and microbiota-based interventions, such as probiotics in topical creams and vaginal microbiota seeding.​

“There is a clear need for more robust research, moving away from merely descriptive studies to understanding the mechanistic role and functions of skin microbiota in disease pathogenesis and treatment. This data should then be used to evaluate the potential for early-intervention strategies, targeted microbiome-based therapies, or as microbial biomarkers to identify high-risk infants.” ​

Source: Wiley Online Library

https://doi.org/10.1111/all.16044​

“The skin microbiome in pediatric atopic dermatitis and food allergy”​

Authors: Elizabeth Huiwen Tham, et al