Wednesday, April 2, 2025
4/2/2025
Early life dysbiosis, and skin barrier function - Abstract The prevalence of atopic diseases such as atopic dermatitis (AD) and asthma are increasing at high rates that can't be explained by purely genetic etiology, indicating the roles of environmental exposures in increasing disease risk. Environmental exposures that alter the risk of allergic diseases (farm exposure, C-section, breast feeding, antibiotic exposure) also influence microbial colonization. Altered microbial composition (aka dysbiosis) at mucosal surfaces, specifically within the perinatal period (<1 year of life) has been linked to increased risk for developing several atopic diseases. Interestingly, atopic diseases are also associated with epithelial barrier dysfunction. Our preliminary data suggest that perinatal dysbiosis is associated with 1) increase in allergen- induced pulmonary responses; 2) a period of increased skin permeability (barrier dysfunction) extending even after resolution of immediate dysbiosis; 3) significant alterations in gene expression in the skin of dysbiotic animals, including dampened TNFα signaling, and predominantly Th2 biased transcriptomic profiles. Interestingly, an isolate of gram negative commensal Roseomonas mucosa identified from healthy volunteers (RMhv) was associated with increased skin barrier function and clinical benefits demonstrated by mouse studies and clinical trials. RMhv-induced improvement in skin barrier function were linked to elevated TNF-related epithelial repair mechanism. Therefore, we hypothesize that by impairing skin barrier function, perinatal dysbiosis can exacerbate sensitivity to the development of skin-associated allergic diseases, and that treatment with a clinically relevant Roseomonas mucosa bacterial isolate is sufficient to protect mice from perinatal dysbiosis- associated defects in skin barrier function. This hypothesis will be tested in two Aims: (1) To determine if perinatal dysbiosis alters susceptibility to the development of skin-associated allergic diseases; (2) To determine if a clinically relevant Roseomonas mucosa isolate identified from healthy volunteers can protect mice against perinatal dysbiosis associated skin barrier dysfunction and house dust mite allergen -induced allergic diseases. Collectively, these studies will elucidate the mechanisms by which perinatal dysbiosis influences skin barrier function and associated allergic diseases.
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