Abstract Body:
Skin health and barrier function are influenced by skin and gut microbiomes through superficial changes and influences on host gene expression. Filaggrin (FLG) is a key protein in this and mutations in its gene are responsible for several xerotic conditions. Prior metabolomics studies have demonstrated a correlation with microbial-derived metabolites, but the causative link is poorly understood. We hypothesize that microbial-derived metabolites influence quantitative FLG expression levels. We investigate whether inter-country differences in the incidence of atopic dermatitis (AD) are related to differential microbial and metabolite profiles of skin and gut.
25,768 skin microbiome samples and 183,432 gut microbiome samples from the USA, Japan, and South Korea were available in the BioCorteX proprietary engines. BioCorteX CarbonMirrorTM platform (v2023-03-30) performed microbiome analyses, inferred the metabolome profile from microbiome composition, and identified influences on host FLG expression.
Skin and gut microbiome and metabolome profiles significantly differed between countries. 3 microbial-derived metabolites influenced FLG expression: hydroquinone, 17beta-estradiol, and calcitriol. Hydroquinone increased FLG expression and was the most prevalent metabolite produced by over 4,800 bacterial taxa. These taxa were in higher abundance in the skin (51%) and gut (63%) of patients from South Korea, a country with comparably lower incidence and severity of AD.
We demonstrate that microbiome-mediated control of FLG expression contributes to heterogeneity in the incidence and severity of AD. This is in contrast with previous literature which has focused on mutation rather than quantitative expression. While hydroquinone is classically a bleaching agent, in-silico concentration and quantification testing are required to understand its differential effects.
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