In vitro wound healing effects of postbiotics derived from the gut microbiota of long-lived blind mole rats, a model of healthy ageing.

Chronic wounds represent a global public health burden to patients and healthcare professionals worldwide. Considering the unmet need for safe and effective therapeutic approaches for wound healing, research on discovering new bioactive materials that support all stages of wound healing is gaining importance. In this study, the wound-healing activity of postbiotics obtained from Limosilactobacillus reuteri EIR/Spx-2, isolated from the gut microbiota of long-lived blind mole rats (Nannospalax xanthodon), was investigated. Our results demonstrated that postbiotics exhibited a strong inhibitory effect against important skin pathogens, eliminated their biofilm formation, and downregulated the expression of genes involved in their quorum-sensing regulatory mechanisms. Furthermore, treatment with postbiotics resulted in a significant increase (23.82% ± 2.11%) in L929 fibroblast cell proliferation. Additionally, postbiotics applied on scratched fibroblast monolayer significantly accelerated the re-epithelialization by 66.78% ± 3.74%. The treatment also increased the mRNA expression and protein levels of COL1A1 in the early healing phase. Moreover, the intracellular ROS levels of L929 cells suppressed by H₂O₂ were significantly reduced, which could be attributed to the content of flavonoids (4.8 mg/g) and phenolic compounds (7.12 mg/g) in postbiotics, as well as their DPPH scavenging activity. After treatment with postbiotics, the mRNA levels of IL-6 (5.77-fold) and TNF-α (1.76-fold) and the amount of NO (79.25% ± 3.18%) were significantly decreased in LPS-induced murine macrophages. The diverse metabolite profile of postbiotics, as characterised using chromatographic techniques, exhibited a strong correlation with their biological activity across all stages of the wound healing process, highlighting their potential as promising candidates for wound healing applications.