Lactobacillus rhamnosus Lcr35(R) as an effective treatment for preventing Candida albicans infection in preclinical models: first mechanistical insights

The increased recurrence of Candida albicans infections is associated with greater resistance to antifungal drugs. This involves the establishment of alternative therapeutic protocols such as the probiotic microorganisms whose antifungal potential has already been demonstrated using preclinical models (cell cultures, laboratory animals). Understanding the mechanisms of action of probiotic microorganisms has become a strategic need for the development of new therapeutics for humans. In this study, we investigated the prophylactic anti-Candida albicans properties of Lactobacillus rhamnosus Lcr35(R) using the in vitro Caco-2 cells model and the in vivo Caenorhabditis elegans model. On Caco-2 cells, we showed that the strain Lcr35(R) significantly inhibited the growth of the pathogen (~2 log CFU.mL-1) and its adhesion (150 to 6,300 times less). Moreover, on the top of having a prolongevity activity in the nematode, Lcr35(R) protects the animal from the fungal infection even if the yeast is still detectable in its intestine. At the mechanistic level, we noticed the repression of genes of the p38 MAPK signaling pathway and genes involved in the antifungal response induced by Lcr35(R) suggesting that the pathogen no longer appears to be detected by the worm immune system. However, the DAF-16 / FOXO transcription factor, implicated in the longevity and antipathogenic response of C. elegans, is activated by Lcr35(R). These results suggest that the probiotic strain acts by stimulating its host via DAF-16, but also by suppressing the virulence of the pathogen.