Microbiome-based therapy for eczema: On the horizon?

Ian A Myles, MD, MPH

Statistics about atopic dermatitis

Bernard A Cohen, MD

Results of preclinical and early clinical trials conducted by investigators at the National Institutes of Health (NIH) showing the effectiveness of using bacteria to treat eczema are paving the way for further study into the potential for microbiome-based therapy to treat this common skin disease.

“I think the days of viewing eczema as a genetic disease that we just can’t find the genes for are coming to an end,” says Ian A. Myles, MD, MPH, assistant clinical investigator, Chief Medical Officer, US Public Health Service Commissioned Corps, National Institutes of Health, National Institutes of Allergy and Infectious Disease, Bethesda, Maryland, and lead author of the study. “Soon enough, the treatment focus will shift to microbiome and environmental modulation instead of expensive drugs that target human pathways.”

The foundation for this shift is coming from research showing the involvement of skin bacteria on the pathogenesis of atopic dermatitis (AD). Although it is known that Staphylococcus aureus is among the underlying pathologic factors creating susceptibility to developing AD, no evidence has yet shown the effectiveness of using these bacteria to treat eczema. In addition, no evidence yet exists that eradicating S aureus from the skin reverses the other pathologic features of eczema including the epithelial barrier function and the innate/adaptive immune balance.

In this new study, Myles and colleagues expand on this research by looking at the potential role of Gram-negative skin bacteria in the pathogenesis and exacerbation of eczema, and, importantly, the effectiveness of these bacteria to treat eczema. In specific, their research isolates a new Gram-negative commensal, Roseomonas mucosa, as a promising candidate for microbiome-based therapy for eczema.

Early results show promise 

In their research article published in JCI Insight,¹ Myles and colleagues discuss preclinical research in mice in which they considered the role of Gram-negative organisms on the skin as playing a role in eczema.  

“When we looked at the distribution of eczema on the body and compared that to the distribution of the Gram-negative organisms on the skin, we saw a clear overlap,” explains Myles. “That made us think that Gram-negative bacteria might play a role in the disease.”

Working from that hypothesis, Myles and colleagues figured out how to culture the bacteria and test it in cell cultures and mice. What they found was that R mucosa emerged as promising bacteria to test in humans based on its ability to improve barrier function, immune balance, kill S aureus, and protect mice from developing eczema in specific models.

To test the therapeutic potential of R mucosa in humans with AD, the investigators conduced an open-label, Phase I/II, safety and activity trial. Called the Beginning Assessment of Cutaneous Treatment Efficacy for Roseomonas in Atopic Dermatitis trial (BACTERiAD I/II), the trial first included 10 adults and later added 5 children with AD. In the trial, live strains of R mucosa isolates were sprayed on eczema of each participant twice weekly for either 6 weeks (adults) or 4 months (pediatric).

The study found a significant reduction in itch, objective rash, and topical steroid requirements in both the adults and children, says Myles. In addition, the study found that strains of R mucosa from healthy people differ in genetics and lipid production compared with strains from patients with eczema.

Finally, the study also looked at topical commercial products that may harm the good strains of R mucosa more than S aureus or other unhealthy strains. According to Myles, the study found several skin products with common chemicals that hurt the healthy bacteria without affecting S aureus or disease-associated Roseomonas.

“Since this is the first-in-human phase trial, we are being cautious, but we have exposed mice to this via injection into the veins, spraying into the eyes, feeding into the stomach, and inoculating directly into the lungs,” he says. “Each time with the mice it was 350,000-fold the exposure that the kids get and literally nothing has happened in the mice-no signs of illness in the mouse, no signs of inflammation or infection in the tissues.”

What’s next?

Commenting on the study, Bernard A. Cohen, MD, professor of Pediatrics and of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, says the study is a good proof-of-concept study but cautions about the preliminary nature of the evidence.

“All the study really does is raise the issue that looking at Gram-negative bacteria should be looked at and may be useful,” he says. “But I don’t think it adds much more to what we already now about the potential benefits of probiotics.”

Which, Cohen points out, is not a lot. “There is a lot of research looking at gut organisms to see what role they may play in worsening or improving atopic dermatitis, but currently the data are pretty mixed,” he says. That said, he sees this line of study as useful and one to pursue more in depth.

“We are very aware that our work is in the early stages and that we have a long way to go before anyone might pick up Roseomonas at their local pharmacy,” says Myles in response. “However, no one had previously identified that this specific strain of bacteria could improve symptoms in AD while being steroid sparing. So cautious optimism seems more appropriate here than pessimism.” 

According to Myles, the investigators are currently finishing the Phase I/II study that they hope to wrap up by this fall. They then intend to discuss what is needed for pursuing a Phase III trial with the US Food and Drug Administration.

References:

1. Myles IA, Earland NJ, Anderson ED, et al. First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis. JCI Insight. 2018;3(9):e120608. Available at: https://insight.jci.org/articles/view/120608. Accessed July 30, 2018.