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Atopic Dermatitis (AD) is a chronic inflammatory skin condition characterised by skin barrier dysfunction and immune dysregulation. Treatment is often difficult and multifaceted, including topical corticosteroids and moisturisers, but recent research has explored ammonium-oxidising bacteria (AOB) as a promising novel approach.
What We Know:
Skin microbiome dysbiosis is a common feature of AD, characterised by low bacterial diversity, high non-Malassezia fungal diversity, an increased abundance of Staphylococcus aureus and Staphylococcus epidermidis, and reduced levels of other bacterial genera, with S. aureus colonisation notably worsening disease severity (Bjerre et al., 2017).
Treating AD involves regular use of emollients, soap-free cleansers, corticosteroids for flare-ups, and broad-spectrum antibiotics targeting S. aureus. Emerging microbiome-based biotherapies, such as probiotics, microbial repopulation, phage therapies, small molecules, monoclonal antibodies, and quorum sensing inhibitors, show promise in addressing S. aureus colonization (Koh, Ong & Common, 2022).
AD is driven by an uncontrolled type 2 inflammatory response involving cytokines IL-5, IL-13, and IL-4, which lead to IgE production, hypersensitivity reactions, itching, and tissue damage. Consequently, therapeutic strategies targeting type 2 cells and their cytokine mediators, such as IL-5, IL-13, and IL-4, have shown promise in managing these conditions (Maura, Elmekki & Goddard, 2021).
Research identifies Nitrosomonas eutropha D23, an ammonia-oxidizing bacteria, as a promising candidate for modulating the T2 pathway. It suppresses Th2 cell polarization and cytokine production, likely via IL-10 and dendritic cell inhibition, suggesting its potential for treating atopic skin diseases (Maura, Elmekki & Goddard, 2021).
Industry Impact and Potential:
AOBiome Therapeutics, Inc., has developed B244: a patented live topical biotherapeutic containing a purified strain of Nitrosomonas eutropha, originally isolated from soil samples, that may help manage AD by reducing pathogenic bacteria like S. aureus (Silverberg et al., 2023).
B244 generates nitric oxide, which helps regulate inflammation and blood vessel dilation by reducing cytokines (IL-4, IL-5, IL-13, IL-31) associated with AD symptoms. Its metabolic, antimicrobial properties, and lack of virulence make it a promising, well-tolerated topical treatment for AD (Silverberg et al., 2023).
Global Phase 3 trials are imminent, with AOBiome partnering with Maruho Co., Ltd. for the treatment's commercialization.
Our Solution:
Sequential is an industry-leading microbiome product developing and testing company based in London, New York and Singapore. Our expertise and customisable services empower businesses to innovate confidently in formulating and investigating products that preserve microbiome integrity, ensuring their efficacy and compatibility for a healthier microbiome.
References:
Bjerre, R.D., Bandier, J., Skov, L., Engstrand, L. & Johansen, J.D. (2017) The role of the skin microbiome in atopic dermatitis: a systematic review. British Journal of Dermatology. 177 (5), 1272–1278. doi:10.1111/bjd.15390.
Koh, L.F., Ong, R.Y. & Common, J.E. (2022) Skin microbiome of atopic dermatitis. Allergology International. 71 (1), 31–39. doi:10.1016/j.alit.2021.11.001.
Maura, D., Elmekki, N. & Goddard, C.A. (2021) The ammonia oxidizing bacterium Nitrosomonas eutropha blocks T helper 2 cell polarization via the anti-inflammatory cytokine IL-10. Scientific Reports. 11 (1), 14162. doi:10.1038/s41598-021-93299-1.
Silverberg, J.I., Lio, P.A., Simpson, E.L., Li, C., Brownell, D.R., Gryllos, I., Ng-Cashin, J., Krueger, T., Swaidan, V.R., Bliss, R.L. & Kim, H.D. (2023) Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial. eClinicalMedicine. 60. doi:10.1016/j.eclinm.2023.102002.
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