Probiotic and Postbiotic Interactions of Lactobacillus Strains with Candida albicans: Antifungal Effects Through...

Background:Candida albicans is the most clinically significant opportunistic fungal pathogen, and the growing resistance to conventional antifungals, particularly azoles and echinocandins, highlights the urgent need for alternative therapeutic strategies. Although lactic acid bacteria (LAB) have shown inhibitory potential against C. albicans, the relative contributions of live probiotics, heat-inactivated postbiotics, and cell-free supernatants (CFSs) have rarely been compared in parallel under physiologically relevant conditions against a clinical oral isolate. Results: This study systematically evaluated the antifungal activity of Lactiplantibacillus plantarum 299V, Lactobacillus delbrueckii subsp. bulgaricus ATCC 11842, and Lactobacillus acidophilus ATCC 4356 using co-culture assays, minimum inhibitory concentration tests, agar well diffusion assays, and optical microscopy. L. plantarum achieved the strongest inhibitory effect in co-culture, reducing C. albicans viability by 2.39 log₁₀ CFU/mL after 24 h, correlating with the greatest acidification of the culture medium. Methods: CFS from L. acidophilus inhibited fungal growth by 79.01% at native pH, declining to 28.35% upon neutralization to pH 7, confirming that antifungal efficacy is largely pH-dependent and driven by undissociated organic acids. At probiotic concentrations of 1 × 10⁹ CFU/mL, all strains completely suppressed fungal growth. Heat-inactivated postbiotics exhibited up to 95.14% inhibition in MIC assays; however, microscopic analysis revealed coaggregation between postbiotic and fungal cells, which likely interfered with optical density measurements. Conclusions: These findings establish that LAB-mediated antifungal activity is multifactorial and assay-dependent, and highlight the importance of distinguishing between probiotic, postbiotic, and CFS effects when developing LAB-based antifungal strategies.