Microbial interplay of recurrent vulvovaginal candidiasis pathobiology

A clinical study has confirmed that the pathophysiology of recurrent vulvovaginal candidiasis (RVVC) relies primarily on Candida albicans (C. albicans)-specific attributes like hyphal morphogenesis, biofilm formation and pathogenesis that differentiate it from other prominent non-albicans C. (NAC) species.

The study also validates the capacity of Lactobacillus crispatus (L. crispatus) to condition a healthy vaginal environment by modulating gene expression in C. albicans, and thus, reduce fungal load in a highly complex biofilm model.

Both the study by McKloud et al1 and the reporting on the study by Papon et al appear in the journal MSystems, a publication of the American Society of Microbiology (ASM).2

Five prominent risk factors for VVC are broad-spectrum antibiotic treatment, high-estrogen-containing contraceptives, sexual activity, pregnancy, and uncontrolled diabetes mellitus.

“From a pathophysiological point of view, it is thought these factors likely result in alterations in the vulvovaginal microenvironment that in turn promotes Candida yeast overgrowth and symptomatic infection,” wrote the reporting authors.

The study authors assessed a panel of 100 clinical isolates: 40 recovered from RVVC and 60 from healthy women. The first series of experiments concluded that Candida burden might be a contributing factor to disease pathology, as well as an indicator of VVC onset and subsequent recurrence.

In fact, the Candida load was found to be significantly lower in healthy samples compared to RVVC samples. “Interestingly, the fungal load appeared to be primarily unaccompanied by a bacterial burden,” wrote the reporting authors.

The study authors also showed that the microbial communities present during RVVC are similar, at the phylum and genus levels, to those found in healthy women, which is consistent with previous studies. A Lactobacillus-dominated population was detected, comprising prominent vaginal anaerobes such as GardnerellaPrevotella and Atopobium.

But the study found that RVVC samples had increased levels of L. iners, which indicate vaginal dysbiosis. These samples also lacked specific L. species that are typically linked to a healthy vaginal microbiome. Hence, protection from local overgrowth of Candida could be provided by resident lactobacilli in the vaginal microenvironment.

In a model of oropharyngeal candidiasis, L. johnsonii was recently found to perhaps dampen C. albicans virulence, both by inhibiting yeast development and by preventing burden of potentially synergistic enterococci.

All of these advancements underscore the pivotal role of specific L. species in modulating Candida proliferation on various human mucosae. Findings also encourage improving women’s health usingprobiotic L.-based therapies to remedy these challenging fungal infections.

Unlike for a single case of VVC, which can often be resolved by a local treatment based on imidazole antifungals or with fluconazole, the recurrent form is treated systemically with triazoles and a local application of imidazoles.

“Unfortunately, therapeutic failures are usually observed, and, in other cases, the treatment tends to only transiently reduce the symptoms during the treatment course,” wrote the reporting authors.

Study data suggests that Candida biofilm formation on the genital epithelium may cause treatment failure and probably contributes to subsequent recurrence of VVC.

It is also likely that the intrinsic tolerance against azoles among several NAC species, including C. glabrata and C. krusei, prevents them from being cleared by antifungal treatment.

References

  1. Papon N, Van Dijck P. A complex microbial interplay underlies recurrent vulvovaginal candidiasis pathobiology. mSystems. Published online October 19, 2021. doi:10.1128/mSystems.01066-21
  2. McKloud E, Delaney C, Sherry L, et al. recurrent vulvovaginal candidiasis: a dynamic interkingdom biofilm disease of Candida and lactobacillus.mSystems. Published online August 10, 2021. doi:10.1128/mSystems.00622-21