A Derivative of Butyric Acid, the Fermentation Metabolite of , Inhibits the Growth of a Strain Isolated from Atopic Dermatitis Patients

The microbiome is a rich source of metabolites for the development of novel drugs. Butyric acid, for example, is a short-chain fatty acid fermentation metabolite of the skin probiotic bacterium (). Glycerol fermentation of resulted in the production of butyric acid and effectively hindered the growth of a () strain isolated from skin lesions of patients with atopic dermatitis (AD) in vitro and in vivo. This approach, however, is unlikely to be therapeutically useful since butyric acid is malodorous and requires a high concentration in the mM range for growth suppression of AD . A derivative of butyric acid, BA-NH-NH-BA, was synthesized by conjugation of two butyric acids to both ends of an -NH-O-NH- linker. BA-NH-NH-BA significantly lowered the concentration of butyric acid required to inhibit the growth of AD . Like butyric acid, BA-NH-NH-BA functioned as a histone deacetylase (HDAC) inhibitor by inducing the acetylation of Histone H3 lysine 9 (AcH3K9) in human keratinocytes. Furthermore, BA-NH-NH-BA ameliorated AD -induced production of pro-inflammatory interleukin (IL)-6 and remarkably reduced the colonization of AD in mouse skin. These results describe a novel derivative of a skin microbiome fermentation metabolite that exhibits anti-inflammatory and bactericidal activity.