Saccharomyces cerevisiae-based probiotic as novel anti-fungal and anti-inflammatory agent for therapy of vaginal candidiasis

Abstract

Previously we demonstrated that the treatment with live Saccharomyces cerevisiae exerts beneficial therapeutic effects against vaginal candidiasis. Here, we address potential mechanisms particularly examining the probiotic capacity to modulate both fungus and host-related factors. We show that the S. cerevisiae-based probiotic markedly affects the expression of virulence traits of Candida albicans such as aspartyl proteinases (SAPs) as well as hyphae-associated proteins Hwp1 and Ece1 in the vaginal cavity. On the host side, the probiotic suppression of the influx of neutrophils caused by the fungus into the vaginas of the mice is likely related to: (1) lower production of interleukin-8; and (2) inhibition of SAPs expression. However, these neutrophils displayed reactive oxygen species hyperproduction and increased killing activity as compared to the neutrophils of placebo-treated mice. There was no evidence of any cytotoxic effect by the probiotic, either when used in vivo on vaginal epithelial cell and organ architecture, or in in vitro in human vaginal epithelium. Inactivated yeast cells did not affect any of the factors above. In summary, the data suggest that the beneficial effect exerted by this S. cerevisiae-based probiotic is the result of its interference with the expression of fungus virulence factors coupled with the modulation of the inflammatory response of the host.

Saccharomyces cerevisiae-Based Probiotics as Novel Antimicrobial Agents to Prevent and Treat Vaginal Infections

“…Indeed, SAPs, through a direct chemotactic activity (Gabrielli et al, 2016), promote the massive recruitment of neutrophils to the vaginal compartment, contributing to exacerbate the pathological inflammation associated to Candida infection (Peters et al, 2014;Vecchiarelli et al, 2015). Additionally, in our experimental models, S. cerevisiae has been shown to influence the host immune response by increasing the antimicrobial property of polymorphonuclear (PMN) cells, in terms of reactive oxygen species (ROS) hyperproduction and killing activity (Gabrielli et al, 2018), which generally appears to be reduced or absent in patients with vaginal candidiasis (Yano et al, 2017). Since ROS play an important role in triggering the extracellular trap (Kenno et al, 2016), which is one of the main mechanisms by which neutrophils can kill non-phagocytosed microorganisms, our results suggest that Saccharomyces may be able to stimulate this process via increasing the ROS production.…”

“…Recently we demonstrated, for the first time, that a S. cerevisiae-based approach may be a very promising and valid tool for both prophylaxis and/or treatment of vaginal diseases such as VVC (Cayzeele-Decherf et al, 2017a;Pericolini et al, 2017;Gabrielli et al, 2018) and BV .…”

“…The beneficial effect of both live and inactivated S. cerevisiae was due to a co-aggregation of Candida and consequently to its inability to adhere to the mucosal surface, protecting the vaginal epithelium from the fungus induced damage . However, only the live and not the attenuated yeast strongly suppressed some of the crucial virulence factors of C. albicans, such as its capacity to switch from the yeast to the hyphal form and the ability to express aspartyl proteases Gabrielli et al, 2018). These effects were related to the ability of the live yeast to significantly inhibit the expression of two important hyphal growth-associated genes, in particular the hyphal wall protein 1 (HWP1) and extent of cell elongation 1 (ECE1), as well as the expression of two secretory aspartyl proteinases (SAPs), SAP2, and SAP6, which play a key role in the immunopathogenesis of vaginal candidiasis (Naglik et al, 2003;Cassone and Cauda, 2012;Gabrielli et al, 2015;Pericolini et al, 2015;Roselletti et al, 2017).…”

Probiotics and prebiotics potential for the care of skin, female urogenital tract, and respiratory tract

“…The probiotic effects on the host and the probiotic suppression of neutrophils influx caused by the fungus into the vaginas of the mice are likely related to lower interleukin-8 (cytokine associated with inflammatory responses) production and inhibition of aspartyl proteinase expression. Besides, there was no evidence of any cytotoxic effect either by the probiotic, when used in vivo, on vaginal epithelial cell and organ architecture, or in in vitro in human vaginal epithelium (Gabrielli et al 2018). Handalishy et al (2014) compared the efficacy of vaginally administered probiotic vaginal tampons with oral metronidazole for the treatment of BV.…”

“…Probiotics can be considered as a promising alternative to antibiotics since they can displace harmful bacteria through various mechanisms. In this regard, several studies have explored the effects of probiotic and prebiotics use on microbiota of other parts of the body, to treat halitosis (Suzuki et al 2014), atopic dermatitis (Wu et al 2012), and allergies related to the respiratory system (Watts et al 2016) and to restore the vaginal microbiota (Gabrielli et al 2018), among others.…”