Background: Alterations of epithelial barrier integrity and immune response play a key role in the pathogenesis of allergic diseases and represent promising targets for nutritional interventions. Selected postbiotics and plant-derived compounds have been proposed as potential modulators of epithelial barrier and immune function. Methods: We investigated the effects of a novel food supplement combining heat-inactivated Lacticaseibacillus rhamnosus GG, butyrate, Quercetin, and Perilla frutescens extracts on epithelial barrier function and innate immunity in an experimental model of the human epithelial gut barrier. Results: Exposure to the food supplement resulted in epithelial barrier integrity enhancement, consisting of increased transepithelial electrical resistance, tight-junction protein expression, mucus production, and enterocyte differentiation. Moreover, the formulation markedly stimulated the expression of the innate immunity peptides β-defensin-2 and cathelecidin LL-37. Conclusions: The novel food supplement induces a beneficial modulation of the epithelial gut barrier and immune response. These findings support its potential use as a functional food strategy to restore mucosal homeostasis and to promote immune tolerance in allergic diseases.

Background: The skin microbiota-derived metabolite butyrate plays a pivotal role in maintaining skin health. Unfortunately, unpleasant sensorial properties and unfavorable physicochemical properties strongly limit the butyrate use in dermatology clinical practice. This study investigates the effects of N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), a butyric acid releaser with neutral sensorial properties on skin keratinocyte function. Methods: Immortalized human keratinocyte cell line (HaCaT cells) was treated with FBA at various concentrations (0.001–1 mM) and time points (6–48 h). Cellular proliferation was assessed using MTT assays, while barrier integrity was evaluated by measuring tight junction proteins (occludin and ZO-1). Oxidative stress was analyzed using ROS assays and Western blot for Nrf2 and NF-κB expression. Markers of differentiation and extracellular matrix proteins were measured via quantitative PCR and wound-healing capability was assessed using a scratch assay. Results: FBA significantly enhanced keratinocyte proliferation at an optimal concentration of 0.1 mM. Tight junction protein expression increased, indicating improved barrier function. FBA reduced oxidative stress by upregulating Nrf2 and suppressing NF-κB activity. It also promoted the expression of differentiation markers (e.g., keratin-1, filaggrin) and extracellular matrix proteins (e.g., collagen type I and elastin). Furthermore, FBA accelerated wound closure, demonstrating its efficacy in enhancing the mechanisms of skin repair. Conclusions: Our results demonstrate that FBA enhances human keratinocyte cell differentiation, proliferation, and skin repair while protecting against oxidative stress. Its potential in cosmetics lies in delivering butyric acid benefits without organoleptic limitations, with possible applications in several skin condition characterized by deficient butyrate production and inflammation, such as atopic dermatitis.