Health Science Reviews

by Israel Oyebade

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) in the United States have shown that topical treatment with a skin bacterium could offer lasting relief for patients with atopic eczema (AE). The group tested the efficacy of topical application of Roseomonas mucosa, a member of the normal skin microbiota, in AE patients and found that it reduced their disease severity, topical steroid requirement, and overgrowth of Staphylococcus aureus, a problematic bacterium in these patients. 

Atopic eczema (also atopic dermatitis) is a chronic allergic disease of the skin marked by dryness, crusting, inflammation and itchiness. It affects about 2-3% of adults and up to 15-20% of children globally. It is caused by an interplay between poor skin barrier function, infectious or environmental agents, and immune dysregulation. It has no cure, but treatments include steroids, moisturizers and other topical drugs such as calcineurin inhibitors. These treatments, however, require daily application and lead to significant costs on affected families. 

“All of the available therapies really just address the host side of the equation”, says Dr. Ian Myles, a coauthor of the study. “So, what we really wanted to ask was whether manipulating the microbiome might provide benefit to patients, and what kind of environmental factors might contribute to this bacterial imbalance”.  

The microbial communities on various body surfaces – the microbiota – are ideally composed of beneficial microbes which promote optimal functioning of body systems. These communities may be disrupted, allowing the establishment of more pathogenic ones that promote inflammation and increase disease susceptibility, a state termed dysbiosis. The profound influence that these microorganisms have on host physiology has led to the development of interventions, such as probiotics, that are aimed at restoring the beneficial microbes. 

“We were able to identify a species of bacteria, Roseomonas mucosa, which in cell cultures and in mouse models was able to kill Staph aureus, which is a bacterium known to exacerbate the disease, and fix some of the immune imbalances that would be associated with atopic dermatitis”, Myles says. 

In an open-label, phase 1 clinical trial, 10 adult and 5 paediatric AE patients were enrolled.  The patients’ overall disease severity, as well as that of the antecubital region, the spot in front of the elbow where treatment would be administered, was measured and assigned a SCORAD value. A predetermined number of live R. mucosa cells suspended in sucrose solution was self-administered by the patients twice weekly. 

This course lasted 6 weeks for the adults, followed by a 4-week washout period. For the younger participants, it continued for 12 weeks, followed by treatment every second day from weeks 13-16. The paediatric group’s washout period was 8 months. During the treatment course, all patients were to continue taking their usual eczema treatments as well. However, by the end of the washout period, the steroid-sparing effects of R. mucosa were evident. 

Treatment was associated with significant reduction in intensity, regional itchiness and antecubital-specific SCORAD. Some patients also experienced responses outside the antecubital region, since they could treat an additional area of their choice. However, treatment of the hands was not associated with clinical benefit, even in patients with antecubital improvement. The authors suggest that this could be due to environmental exposures on the hands that promote dysbiosis, such as increased contact with topical antimicrobials. In addition, no patients had adverse reactions. 

Previous clinical studies on eczema had noted placebo effects of up to 30%, leading to agreement that only improvements greater than 50% were statistically suggestive of treatment activity. In this study, 10 of the combined 15 patients reached this threshold, for regional or total SCORAD. All the adult patients who appeared responsive to treatment reported sustained or even additional improvement after the washout phase. The washout phase for the paediatric group is ongoing. 

“Then we went from the microbiome and started to look at some of the environmental factors that might create this imbalance in your skin bacteria”, said Dr. Myles. “And we found that certain preservatives that can be found in lotions and creams and soaps, even some of the things that you might use to treat atopic dermatitis actually killed the healthy strains of Roseomonas, while allowing for the growth of disease-associated strains and Staph aureus”. 

The group grew bacteria on disks impregnated with substances like parabens, which the patients may be exposed to. Some of these substances inhibited the growth of healthy R. mucosa strains more than S. aureus. However, the authors cautioned that more studies are needed to clarify the exposures that promote the dysbiosis linked to eczema, and that no causal link between the tested substances and eczema symptoms, or even dysbiosis, can be inferred from their results. 

In their preclinical study, Myles and colleagues had shown in cell models that healthy strains of R. mucosa improved barrier function, innate immune activation, and through lipid secretions, inhibited S. aureus. They also found that it improved outcomes in a mouse model of atopic eczema. The group believes that the bacterium may be providing benefit through various mechanisms that target epithelium function, immune balance, and S. aureus growth. 

The research group’s probe into benefits of this bacterium is one of many efforts to understand how the microbiome can be harnessed for human health. While Myles’ group and others are interested in developing microbiota-based therapeutics, the benefits of the microbiome also extend to diagnostics and the prevention of disease. It is surprising that our bodies do not just consist of us, but are ecosystems themselves, with relationships that may be quite useful. 

“Although these early results are promising, we’re going to need a large-scale, placebo-controlled trial to really establish this therapy” 

“The major appeal of this is that its going to be inexpensive, because you can literally grow the drug. But one of the other things that would be exciting is if you could colonize the patient”, Myles said.  “If we are able to set up colonization, what that could mean is that by intervening early, you could spare the patient years of daily therapy.”  

References

Ian A. Myles, et al. (2018). First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis. JCI Insight, 1-13.

Ian A. Myles, et al. (2016). Transplantation of human skin microbiota in models of atopic dermatitis. JCI Insight, 1-10.