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Biotics battle vaginal fungal biofilms

Eradicating vaginal biofilms involving Candida species requires synergistic combinations of antifungal drugs with pre-, pro-, post-, and synbiotics, according to a recent Frontiers in Microbiology review.1

“Over the past decade,” said corresponding author Leslie Thian Lung Than, PhD, “fungal biofilms have been implicated in the development of vulvovaginal candidiasis (VVC).” He is an associate professor in the Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM) in Serdang, Malaysia.1

Normally, Candida species are opportunistic fungal pathogens found in healthy vaginal microflora and pose no threat to the host. However, conditions such as pH changes, immunosuppression, and poor hygiene can shift the bacterial balance away from a healthy predominance of lactobacilli, leading to fungal overgrowth and invasiveness.

Vaginal fungal biofilms could form on the vaginal epithelium (biotic biofilms) and on implantable polymeric devices such as vaginal rings (abiotic biofilms), Than told Contemporary OB/GYN®. “As fungal biofilms are generally less susceptible to the current antifungal arsenal, recalcitrant persister cells within the biofilms often survive, and this can have impact in recurrent VVC and persistent infections.” The inability of antifungals to penetrate fungal biofilms could lead to development of antifungal resistance, he added, which prevents complete eradication of fungal biofilms, resulting in a vicious cycle.

Additional causes for antimicrobial resistance include overuse of over-the-counter agents. Although these products can treat uncomplicated VVC effectively,2 he said, easy access leads to unsupervised self-medication, which physicians should discourage in patients with presumed VVC.

“As for complicated VVC including recurrent VVC, fungal biofilm-associated VVC, and non-Candida albicans VVC,” said Than, “it is important to identify the Candida species via a vaginal culture or PCR.” Because some non-C. albicans Candida species (e.g., Candida glabrata) are intrinsically resistant to azoles, he said, providers could perform antifungal susceptibility testing before prescribing antifungals.

For VVC that resists standard antifungal therapy, authors recommended combining antifungals with adjuvants such as biotics, boric acid, allicin, and tea tree oil. “Combining existing antifungals with adjuvant therapy using the biotics family could be a promising treatment regimen for better management of complicated vaginal fungal infections,” said senior author Shu Yih Chew, PhD. He is a postdoctoral research fellow, Department of Medical Microbiology, UPM.

Administered orally or vaginally, Lactobacillus and Bifidobacterium represent the most common lactic acid bacteria (LAB) used for vaginal probiotics. “The ability of probiotics to colonize and replenish the vaginal ecosystem creates an environment conducive to the long-term restoration of the host’s indigenous LAB, thereby decreasing the risk of recurrent attacks,” Chew said. Probiotics also avoid collateral effects of conventional antifungals, reducing the chances of developing drug-resistant mutations.

Prebiotics such as oligosaccharides enhance the growth and viability of probiotics. Synbiotics combine both probiotics and prebiotics in a form of synergism.

Postbiotics is a broad term to describe bioactive compounds and metabolites secreted by probiotics during fermentation that are potentially as effective as the probiotics themselves, Chew said. “Postbiotic components including bacteriocin, biosurfactants, LAB cell-free supernatant, and organic acids also represent prospective strategies for the treatment of vaginal fungal infections.”3-6

REFERENCES:

1. Boahen A, Than LTL, Loke YL, Chew SY. The antibiofilm role of biotics family in vaginal fungal infections. Front Microbiol. 2022 May 26;13:787119. doi: 10.3389/fmicb.2022.787119. PMID: 35694318; PMCID: PMC9179178

2. Chew SY, Than LT. Vulvovaginal candidosis: contemporary challenges and the future of prophylactic and therapeutic approaches. Mycoses. 2016;59(5):262-273. doi:10.1111/myc.12455

3. Umar Meleh H, Choo S, Mohd Desa MN, et al. Isolation and safety characterisation of lactobacilli strains with antimicrobial properties as potential probiotics for human use. LWT. 2020;131:109796. doi:10.1016/j.lwt.2020.109796

4 De Gregorio PR, Parolin C, Abruzzo A, et al. Biosurfactant from vaginal Lactobacillus crispatus BC1 as a promising agent to interfere with Candida adhesion. Microb Cell Fact. 2020; 19:133. doi:10.1186/s12934-020-01390-5

5. Hefzy EM, Khalil MAF, Amin AAI, Ashour HM, Abdelaliem YF. Bacteriocin-like inhibitory substances from probiotics as therapeutic agents for Candida vulvovaginitis. Antibiotics. 2021; 10(3):306. doi:10.3390/antibiotics10030306

6. Parolin C, Abruzzo A, Giordani B, et al. Anti-Candida activity of hyaluronic acid combined with Lactobacillus crispatus lyophilised supernatant: a new antifungal strategy. Antibiotics. 2021;10(6):628. doi: 10.3390/antibiotics10060628