HOST-MICROBIOTA INTERPLAY REGULATES EPITHELIAL BARRIER FUNCTION AND WOUND HEALING

Abstract

Skin microbiome emerged as an important factor which can balance tissue repair process and wound healing. Recent evidence suggest that intracellular bacterial localization could be associated with the aberrant healing observed in patients with chronic wounds, while therapeutics targeting intracellular bacteria remain limited. Probiotic lactobacilli and their bioactive lysates (postbiotics) are well known for their role in maintenance of gut epithelial homeostasis. Hence, in this study we focused to understand the mechanisms of cutaneous response to fourteen postbiotics derived from different lactobacilli to reduce intracellular Staphylococcus aureus colonization and promote healing. Latilactobacillus curvatus BGMK2-41 demonstrated the most efficient capability to reduce intracellular infection by S. aureus in keratinocytes in vitro and infection of human skin explants. Reduction of bacterial number was followed by upregulation of the expression of antimicrobial response genes. Furthermore, BGMK2-41 postbiotic treatment stimulates keratinocyte migration in vitro and increases expression of anti-inflammatory cytokine IL-10, promotes wound closure and strengthens the epidermal barrier via upregulation of tight junction proteins in a human ex vivo wound model. Altogether, this study provided evidence that postbiotics could stimulate fortification of epithelial barrier to suppress dissemination of intracellular pathogens which can be used as a novel approach to treat dermatologic and wound healing disorders associated with persistent infections.