Infection control and anti-apoptotic effect of Lactobacillus paracasei derivatives on fibroblasts through modulation of BCL2 transcription.

Limitations in current wound management strategies of infections with antibiotic resistance Pseudomonas aeruginosa, have prompted the search for alternative therapeutic approaches. Employing the probiotic-derived products was the approach of this investigation by using probiotic cell-free supernatants (CFSs) through controlling infections and mitigating the cytotoxic effects of pathogenic metabolites on fibroblast survival. Four probiotic CFSs were analyzed using antimicrobial broth microdilution assays, GC-MS analysis, antioxidant activity assays, and hemolysis assays. The effects of probiotic CFSs, both alone and in combination with P. aeruginosa CFS, were investigated using cellular and molecular assays. Lactobacillus paracasei CASEI431 exhibited antimicrobial activity against Staphylococcus aureus ATCC 25,923, and P. aeruginosa ATCC 27,853, with a minimum inhibitory concentration of 6.25 mg/mL. However, Bifidobacterium animalis CFS showed the strongest toxicity to fibroblast cells, while L. paracasei CFS had the most positive effect on fibroblast proliferation. Following treatment of cells with the pathogenic CFS, viability of HFFs was significantly reduced. Although co-treatment of cells with L. paracasei and pathogenic CFSs did not significantly increase cell viability by MTT assay, it caused a significant upregulation of the anti-apoptotic gene BCL2 by approximately 3-fold and 36-fold after 24 and 72 h, respectively comparing pathogenic CFS treatment alone. Overall, this study suggests probiotic derived products as a complementary therapy accelerating chronic wounds healing through infection control. However, further research including in vivo studies, comprehensive metabolite profiling, and elucidation of the underlying signaling pathways are necessary to validate and expand upon these findings.