B244 inhibits Th2 immune polarization in human primary immune cells in both the active and the inactive state.
CAMBRIDGE, Mass., July 15, 2021 /PRNewswire/ — AOBiome Therapeutics, Inc. (“AOBiome”), a leading clinical-stage microbiome company focusing on inflammatory conditions, announced new findings indicating a link between Ammonia Oxidizing Bacteria (AOB) and the human immune system. The company’s lead clinical asset, B244, is composed of a unique patented single strain of AOB and is currently being evaluated in a Phase 2b clinical trial for pruritus (itch) associated with atopic dermatitis. This trial and its previously successful Phase 2b acne trial show the breadth of this immunomodulation as it pertains to skin disease.
Atopic Dermatitis, and other atopic diseases, have been steadily increasing since the mid 20th century, a rise that has been linked to modern hygienic lifestyles that limit exposure to microbes and immune system maturation. Overactive type 2 CD4+ helper T (Th2) cells are known to be closely associated with atopy and represent a key target for treatment. AOBiome reports that the ammonia oxidizing bacteria (AOB) Nitrosomonas eutropha B244, an environmental microbe that is not associated with human pathology, effectively suppresses the polarization of Th2 cells and production of Th2-associated cytokines (IL-5, IL-13, & IL-4) by human peripheral blood mononuclear cells (PBMC). They show that AOB inhibit Th2 cell polarization not through Th1-mediated suppression, but rather through an IL-10 mediated mechanism that interferes with the activation of dendritic cells, as evidenced by a reduction in Major Histocompatibility Complex Class II (MHC II) and CD86 expression following AOB treatment. This is the first report of immunomodulatory properties of AOB and supports the development of AOB as a potential therapeutic for atopic diseases.
Since the mid twentieth century, the prevalence of atopic diseases has been steadily increasing with more than 200 million people worldwide suffering from diseases such as asthma, allergic rhinitis, or food allergies. The rapid increase in atopy prevalence cannot be explained by changes in population genomics. Rather, the association with westernized societies suggests that environmental factors such as diet, antibiotic exposure, and other modern hygienic lifestyles play a crucial role in the etiology of these conditions.
Reduction of Th2-associated cytokines reveals a compelling link to pruritus (itch). Increased levels of IL-4 and IL-13 are associated with itch, and antibodies which target blocking their receptors, have been utilized as therapeutics for atopic disease. As non-pathogenic bacteria, AOB represent a unique tool to reduce atopy-inducing cytokines without side effects and black box warnings associated with current standards of care.
“The reduction of the TH2 pathway is helping us understand how ammonia oxidizing bacteria helps temper immune response. This supports both our previous clinical trial results and our current 576 patient Phase 2b study of pruritus associated with atopic dermatitis. We look forward to results in Q4 of this year,” said President & CEO, Todd Krueger.
The paper “The ammonia oxidizing bacterium Nitrosomonas eutropha blocks T helper 2 cell polarization via the anti-inflammatory cytokine IL-10” is available on Nature.com at: https://www.nature.com/articles/s41598-021-93299-1
“The demonstration of downregulation of the inflammatory response with topical probiotic AOB presents a wonderful clinical opportunity to treat a large group of patients with an approach that may have virtually no side effects,” said Peter Lio, MD, FAAD, Clinical Assistant Professor of Dermatology & Pediatrics, Northwestern University Feinberg School of Medicine and founding director of the Chicago Integrative Eczema Center.
Additional information regarding AOBiome’s ongoing clinical programs may be found at https://clinicaltrials.gov
About AOBiome Therapeutics, Inc.
AOBiome Therapeutics, Inc. is a Cambridge, MA-based life sciences company focused on transforming human health by developing microbiome-based therapies for local, nasal and systemic inflammatory conditions. Founded in 2012 by PatientsLikeMe founder Jamie Heywood and MIT-trained Chemical Engineer David Whitlock, AOBiome is advancing a pipeline of multiple, clinical-stage therapeutic candidates. Learn more at www.aobiome.com.
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1 Hanifin J, Reed M. A Population-Based Survey of Eczema Prevalence in the United States. Dermatitis. 2007;18(2):82-91. doi:10.2310/6620.2007.06034.