Application of urolithin A – a postbiotic metabolite produced by human gut microbiota, in topical treatment of atopic dermatitis

Urolithin A (UA) is a postbiotic metabolite produced by human gut microbiota from ellagitannins. Unlike ellagitannins, UA has well-documented bioavailability, and its anti-inflammatory properties were proven in many studies. However, following absorption in the intestine, UA is conjugated with glucuronic acid and hence is present in the form of inactive phase II metabolites in tissues and bloodstream. Above limitations related to oral application of ellagitannins and UA have led to attempts to use its anti-inflammatory potential in a topical formulation applied to the skin. Composition of an ointment was based on white petrolatum with 0.2% or 1.0% UA. The formulation containing 1.0% hydrocortisone was applied as a positive control. The induction of dermatitis on the ear skin of Wistar rats involved local infiltration of 2,4-dinitrochlorobenzene. Ear edema was significantly reduced after the introduction of the topical treatment with both concentrations of UA and hydrocortisone. Behavioral assessment showed a reduction in scratching rate for both UA and hydrocortisone, however the effect was significantly more pronounced for UA. The observed anti-inflammatory activity of UA was associated with immune cells count decrease and attenuation of pathohistological changes in the examined skin lesions. In vitro experiments using human fibroblasts (NHDF) and keratinocytes (HaCaT) indicated attenuation of LTA-induced inflammatory response. The obtained results indicate the potential of application a composition containing UA in topical therapy of skin inflammations, in treatment of which hydrocortisone or other steroids are currently used. Acknowledgment Fig. 1 This work has been financially supported by Lider XI Project (LIDER/31/0118/L-11/19/NCBR/2020), National Centre for Research and Development Poland. # Publication History Article published online: 12 December 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany