Action mechanisms of probiotics on Candida spp. and candidiasis prevention: an update

Candida albicans is the most important Candida species causing vulvovaginal candidiasis (VVC). VVC has significant medical and economical impact on women's health and wellbeing. While current antifungal treatment is reasonably effective, supportive and preventive measures such as application of probiotics are required to reduce the incidence of VVC. We investigated the potential of the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 towards control of C. albicans. In vitro experiments demonstrated that lactic acid at low pH plays a major role in suppressing fungal growth. Viability staining following cocultures with lactobacilli revealed that C. albicans cells lost metabolic activity and eventually were killed. Transcriptome analyses showed increased expression of stress-related genes and lower expression of genes involved in fluconazole resistance, which might explain the increased eradication of Candida in a previous clinical study on conjoint probiotic therapy. Our results provide insights on the impact of probiotics on C. albicans survival.

The female vaginal environment contains diverse microorganisms, and their interactions play significant roles in health and disease. Lactobacillus species are the predominant vaginal microorganisms in healthy women and relevant as a barrier to defense against pathogens, including Candida albicans. The yeast-to-hyphae transition is believed to be a determinant of C. albicans pathogenesis. In this study, we investigated the effects of vaginal isolates of L. crispatus (seven strains), L. gasseri (six strains), and L. jensenii (five strains) on growth, hyphal formation and virulence-related genes expression of C. albicans ATCC 10231. We found that the L. crispatus showed the most significant antimicrobial activities in microplate-based liquid medium assay (P 60%. The effects might be due to their productions of some secretory antimicrobial compounds in addition to H2O2 and organic acids. Furthermore, each of the CFS of Lactobacillus strains was found to significantly suppress the yeast-to-hyphae transition of C. albicans under hyphae-inducing conditions (RPMI 1640 medium supplemented with 10% fetal bovine serum). The hyphae inhibition rates of C. albicans treated by CFS from L. crispatus, L. gasseri, and L. jensenii were 88.3 ± 3.02%, 84.9 ± 6.0%, and 81.9 ± 6.2%, respectively. Moreover, the expression of hyphae-specific genes (ALS3, HWP1, ECE1, EAP1, and SAP5) and transcriptional regulatory genes (EFG1, TEC1, and NRG1) were analyzed using quantitative real-time PCR. The results demonstrated that L. crispatus CFS significantly down-regulated the expression of hyphae-specific genes ALS3 (0.140-fold)), HWP1 (0.075-fold), and ECE1 (0.045-fold), while up-regulated the expression of the negative transcriptional regulator gene NRG1 with 1.911-fold. The antimicrobial compounds from L. crispatus B145 against Candida growth were heat stable and protease resistance, but those against hyphal formation were partially sensitive to the same treatments. Our novel findings suggest that L. crispatus, a dominant Lactobacillus species associated with a healthy vagina, could strongly inhibit C. albicans growth and hyphal formation. L. crispatus might repress the expression of hyphae-specific genes (ALS3, HWP1, and ECE1) in a NRG1-dependent manner. Besides, L. crispatus B145 is highly worthwhile for probiotic investigation.

Candida yeasts are generally found in the vaginal microbiota; however, disruption of the balance maintained by host factors and microorganisms results in vulvovaginal candidiasis (VVC). This study evaluated the antagonistic activity of vaginal Lactobacillus spp. on Candida albicans to verify whether active compounds of Lactobacillus spp. had antifungal and antivirulence activity. The antagonism assay showed that 15 out of 20 Lactobacillus strains had an inhibitory effect on C. albicans. Biosurfactants displayed surface-tension-reducing activity, with the best value obtained for Lactobacillus gasseri 1. Lactobacillus rhamnosus ATCC 9595, Lactobacillus acidophilus ATCC 4356, and Lactobacillus paracasei 11 produced biosurfactants that decreased C. albicans adhesion and disrupted biofilm formation. The best results were obtained in the pre-incubation assay for L. gasseri 1 and L. paracasei 11. Overall, Lactobacillus strains showed significant anti-Candida activity, and their biosurfactants exhibited considerable anti-adhesion and antibiofilm activity against C. albicans. To be considered safe for use in vivo, the safety of biosurfactant (BS) should be investigated using cytotoxicity assays.