Probiotic skin therapy improves eczema in children, NIH study suggests

An experimental treatment for eczema that aims to modify the skin microbiome safely reduced disease severity and increased quality of life for children as young as 3 years of age, a National Institutes of Health study has found. These improvements persisted for up to eight months after treatment stopped, researchers report Sept. 9 in Science Translational Medicine.

Inner elbow of a child with eczema before Roseomonas mucosa therapy (left) and after four months of treatment (right).NIAID

Atopic dermatitis, commonly called eczema, is a chronic inflammatory skin disease characterized by dry, itchy skin and rashes. The disease is most common in children and is linked to an increased risk of developing asthma, hay fever and food allergy. While available treatments can help manage eczema symptoms, current options can be costly, and many require multiple daily applications.

The experimental therapy contains strains of live Roseomonas mucosa—a bacterium naturally present on the skin—originally isolated from healthy volunteers and grown under carefully controlled laboratory conditions. For four months, clinical trial participants or their caregivers periodically applied this probiotic therapy to areas of skin affected by eczema.

“A child suffering from eczema, which can be itchy, painful and distracting for the child, also is very difficult for the entire family,” said Anthony S. Fauci, M.D., director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID), which led the study. “These early-stage findings suggest that R. mucosa therapy may help relieve some children of both the burden of eczema symptoms and the need for daily treatment.”

Numerous genetic and environmental factors contribute to eczema, and scientists are learning more about the role that the skin’s microbiome plays in this condition. In 2016, NIAID researchers reported that R. mucosa strains isolated from healthy human skin improved outcomes in cell culture and mouse models of eczema.

To build on these preclinical findings, NIAID launched a Phase 1/2 clinical trial at the NIH Clinical Center in Bethesda, Maryland, to assess the safety and potential benefit of R. mucosa therapy in people with eczema. Interim results reported in 2018 for 10 adults and five children aged 9 to 14 years indicated that the treatment was safe and associated with reduced eczema severity. Since then, the trial has enrolled an additional 15 children, for a total of 20 children with mild to severe eczema ranging in age from 3 to 16 years.

Twice weekly for three months and every other day for an additional month, children or their caregivers sprayed a solution of sugar water containing live R. mucosa onto areas of skin with eczema. For the first 15 children enrolled in the study, the dose of live R. mucosa was gradually increased each month. The last five children to enroll received the same dose throughout the four-month treatment period. Regardless of dosing strategy, no serious adverse events were attributed to the therapy.

“Most children in the study experienced substantial improvements in their skin and overall wellbeing following R. mucosa therapy. Encouragingly, the therapeutic bacteria stayed on the skin and continued to provide benefit after therapy stopped,” said NIAID’s Ian Myles, M.D., principal investigator of the trial. “These results support a larger study to further assess the safety and effectiveness of this experimental treatment by comparing it with a placebo.”

Seventeen of the 20 children experienced a greater than 50% improvement in eczema severity following treatment. Improvement occurred on all treated skin sites, including the inner elbows, inner knees, hands, trunk and neck. The scientists also observed increases in the skin’s barrier function—its ability to seal in moisture and keep out allergens. Additionally, most children needed fewer corticosteroids to manage their eczema, experienced less itching, and reported a better quality of life following the therapy. These benefits persisted after treatment ended, and the therapeutic R. mucosa strains remained on the skin for up to eight months.

The NIAID researchers next set out to better understand how R. mucosa therapy improves eczema symptoms. They found that treated skin had increased microbial diversity and reduced levels of Staphylococcus aureus—a bacterium known to exacerbate eczema.

In addition to imbalances in the microbiome, the skin of people with eczema is deficient in certain lipids, or oils. By conducting experiments in cell and animal models of eczema, the NIAID scientists found that a specific set of lipids produced by R. mucosa strains isolated from healthy skin can induce skin repair processes and promote turnover of skin tissue. Study participants had increased levels of these lipids on their skin after treatment with R. mucosa.

The researchers emphasize that additional studies are needed to further elucidate the mechanism of R. mucosa therapy and to explore whether genetic or other factors may explain why some participants did not benefit from the experimental treatment.

Scratching the Skin Primes the Gut for Allergic Reactions to Food, Mouse Study Suggests

NIH-Funded Research Illuminates Relationship Between Eczema and Food Allergy

Scratching the skin triggers a series of immune responses culminating in an increased number of activated mast cells(link is external)—immune cells involved in allergic reactions—in the small intestine, according to research conducted in mice.

This newly identified skin-gut communication helps illuminate the relationship between food allergy and atopic dermatitis (a type of eczema), a disease characterized by dry, itchy skin. The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and led by researchers at Boston Children’s Hospital.

Atopic dermatitis is a strong risk factor for developing food allergy, but the precise relationship between the two conditions remains unclear. As itching is a major symptom of atopic dermatitis, people with the disease, particularly babies, often scratch their skin. The current study proposes that scratching the skin instigates mast-cell expansion in the intestine.  

The researchers found that some cells in the skin respond to scratching—simulated by applying and removing small strips of tape on the skin of mice—by producing a cell-signaling protein called IL-33, which enters the bloodstream. When IL-33 reaches the gut, it works in concert with IL-25, a protein secreted by cells in the lining of the intestine, to activate type 2 innate lymphoid cells (ILC2s). Activated ILC2s make two additional cell-signaling proteins, IL-13 and IL-4, which were found to be responsible for the expansion of intestinal mast cells. 

The researchers also found that as mast cells expanded, the intestinal lining became more permeable, making it easier for allergens to enter the tissues. Notably, mice that underwent tape stripping had more severe reactions to food allergen than mice that did not. Finally, the researchers found that intestinal biopsies from four children with atopic dermatitis contained more mast cells than those from four children without the condition. 

Although additional work is needed to determine the relevance of the findings to humans, the researchers suggest that interventions to limit itching potentially could lessen the severity of food allergy among people with atopic dermatitis.

Scientists Identify Unique Subtype of Eczema Linked to Food Allergy

Children with Both Conditions have Abnormal Skin Near Eczema Lesions, NIH-Funded Research Finds

A researcher demonstrates the minimally invasive collection of skin samples using small, clear tape strips.
Credit: National Jewish Health

Atopic dermatitis, a common inflammatory skin condition also known as allergic eczema, affects nearly 20 percent of children, 30 percent of whom develop food allergies.

Scientists have now found that children with both atopic dermatitis and food allergy have structural and molecular differences in the top layers of healthy-looking skin near the eczema lesions, whereas children with atopic dermatitis alone do not.

Defining these differences may help identify children at elevated risk for developing food allergies, according to research published online today in Science Translational Medicine. The research was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. 

“Children and families affected by food allergies must constantly guard against an accidental exposure to foods that could cause life-threatening allergic reactions,” said NIAID Director Anthony S. Fauci, M.D. “Eczema is a risk factor for developing food allergies, and thus early intervention to protect the skin may be one key to preventing food allergy.” Children with atopic dermatitis develop patches of dry, itchy, scaly skin caused by allergic inflammation.  Atopic dermatitis symptoms range from minor itchiness to extreme discomfort that can disrupt a child’s sleep and can lead to recurrent infections in scratched, broken skin.

A drawing of skin and a hair follicle. In this study, scientists analyzed the outermost layer of the skin, the stratum cornea, highlighted here in yellow.Credit: NIAMS, NIH

The study, led by Donald Y.M. Leung, M.D., Ph.D., of National Jewish Health in Denver, examined the top layers of the skin, known as the stratum corneum, in areas with eczema lesions and in adjacent normal-looking skin. The study enrolled 62 children aged 4 to 17 who either had atopic dermatitis and peanut allergy, atopic dermatitis and no evidence of any food allergy, or neither condition. Investigators collected skin samples by applying and removing small, sterile strips of tape to the same area of skin. With each removal, a microscopic sublayer of the first layer of skin tissue was collected and preserved for analysis. This technique allowed researchers to determine the skin’s composition of cells, proteins and fats, as well as its microbial communities, gene expression within skin cells and water loss through the skin barrier.

Researchers found that the skin rash of children with both atopic dermatitis and food allergy was indistinguishable from the skin rash of children with atopic dermatitis alone. However, they found significant differences in the structure and molecular composition of the top layer of non-lesional, healthy-appearing skin between children with atopic dermatitis and food allergy compared with children with atopic dermatitis alone. Non-lesional skin from children with atopic dermatitis and food allergy was more prone to water loss, had an abundance of the bacteria Staphylococcus aureus, and had gene expression typical of an immature skin barrier. These abnormalities also were seen in skin with active atopic dermatitis lesions, suggesting that skin abnormalities extend beyond the visible lesions in children with atopic dermatitis and food allergy but not in those with atopic dermatitis alone.

“Our team sought to understand how healthy-looking skin might be different in children who develop both atopic dermatitis and food allergy compared to children with atopic dermatitis alone,” said Dr. Leung. “Interestingly, we found those differences not within the skin rash but in samples of seemingly unaffected skin inches away. These insights may help us not only better understand atopic dermatitis, but also identify children most at risk for developing food allergies before they develop overt skin rash and, eventually, fine tune prevention strategies so fewer children are affected.”

Allergy experts consider atopic dermatitis to be an early step in the so-called “atopic march,” a common clinical progression found in some children in which atopic dermatitis progresses to food allergies and, sometimes, to respiratory allergies and allergic asthma. Many immunologists hypothesize that food allergens may reach immune cells more easily through a dysfunctional skin barrier affected by atopic dermatitis, thereby setting off biological processes that result in food allergies. 

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Reference:  D Leung et al. Non-lesional skin surface distinguishes atopic dermatitis with food allergy as unique endotype. Science Translational Medicine DOI: 10.1126/scitranslmed.aav2685 (2019).