Vaginal candida infections
Vaginal candida infections (VCI) such as vaginal (occurring inside the vagina) or vulvovaginal (occurring on the vulva) candidiasis, are common infections affecting an estimated 75% of sexually active women at least once in their lifetime. Physical symptoms include but are not limited to vaginal itching, dyspareunia, a burning sensation, and a thick lumpy white discharge1 2. VCI represent a heavy negative emotional and sexual burden for patients2, especially as approximately 50% of women will develop a second episode, and 5% of those women will suffer from further recurrences2.
Risk factors for VCIs include antibiotic use3, use of hormonal (and other) contraconceptives4 5, sexual intercourse6, use of vaginal lubricants7, vaginal douching8, menstruation9 10 11 12, pregnancy13, and stress14 15 16. The common feature of these risk factors is that they can cause an imbalance or dysbiosis in the vagina. If the natural vaginal microbiome is out of balance, it cannot prevent overgrowth of pathogens2 17, thus women with a dysbiotic vaginal microbiome are likely at higher risk of developing various symptomatic infections18.
Fungi are important microorganism of the vaginal ecosystem in healthy women19 20 21 and Candida spp. colonize approximately from 20% to 65% of women without causing any symptoms19. However, the transition from normal vaginal resident to symptomatic infection is poorly understood and usually involves the combination of host inflammation, microbiome dysbiosis, and Candida spp. virulence factors.
The human vagina is inhabited by over 50 different inter-kingdom species22 23, including anaerobic bacteria (mostly Lactobacillus spp.), viruses, and fungi19 21. One of the key functions of this microbiome is to maintain a low pH and thus prevent various pathogenic microorganisms from dominating the niche. It is thought that vaginal microorganisms originate in general from the GI tract24 25 by migrating across the perineum26, which acts as an extra-vaginal reservoir, further explaining the co-morbidities between GI complaints and urogenital infections noted in some patients27. In general, vaginal microbiome research in humans focuses on identification of bacterial and viral microborganisms with very little emphasis on exploring the natural fungal population19 20 21. Thus a majority of vaginal mycobiome studies are still limited to the pathology context and not to understanding how they contribute to health.
The Candida spp. present in a healthy vaginal microbiome include Candida albicans, Candida glabrata, Candida krusei, or Saccharomyces spp.19 21 and it is thought that in VCI, they outcompete the other vaginal microbiome residents to dominate the vaginal niche. The findings of Guo et al. (2012) demonstrated an increase in vaginal funcal diversity in patients with recurrent VCI compared to health volunteers. This subsequent dysbiosis characterized by an increased proportion of C. albicans was also correlated with a reduced proportion of Saccharomyces spp. and other uncultured fungi. This implies that Candida spp. are in fact pathobionts, able to live peacefully in the vagina or able to become virulent pathogens and cause infections.
Interestingly enough, the pathology of VCI can be partly explained by the three main cellular forms or morphologies of Candida: yeast, pseudohyphae, and hyphae. The last form is the most virulent, while yeast and pseudohyphae are the reproductive and intermediate transitional forms, respectively. It should be noted that each morphology is genetically, metabolically, and physically different and that Candida spp. have evolved so that they can easily switch between forms29 30. The symptoms associated with VCIs are thought to be caused by an overgrowth of the hyphal morphology which causes inflammation31, forms biofilms32 and penetrates deep into vaginal epithelial tissue1 2. When viewed in a wet mount slide, vaginal discharge from a VC patient reveals budding yeast cells and psuedohyphae alongside mature hyphae and activated immune cells33.
The presence of multiple simultaneous morphologies make it extremely difficult to eradicate this organism especially because therapies often only target one morphology34. Another challenge is when Candida spp. reside in a biofilm; Candida biofilms show uniform resistance to a wide spectrum of the currently available antimycotics35. This could be explained in part because the physical biofilm matrix slows down the penetration and diffusion of drugs and thus only the top few biofilm layers are targeted, leaving the remaining biofilm to persist, regrow, and dominate. These particular hallmark virulence factors of Candida endow it with a number of mechanisms by which it can evade the immune system and antimycotic treatment. With high recurrence rates, high treatment failure rates, and the adverse effect on quality of life, there is a need to develop adjuncts and alternative treatments for VCI.
Studies have shown that probiotics can increase the effectiveness of anti-fungal therapy2 40, that they are safe and have minimal-to-no side effects2 37 38 39. The evidence suggesting that VCI is a result of, or causes, a disruption of the vaginal microbiome, cites research that targets VCI infections or prophylaxis using microbiome management options such as probiotics2. Pre-clinical data show that probiotics can increase the effectiveness of anti-fungal therapy2 39 and inhibit the growth and virulence of urogenital pathogens23. The efficacy of probiotics to populate the vagina and prevent or treat infection has been shown for multiple endpoints, including adjuncts together with antimicrobial treatment to improve cure rates and prevent recurrences23. An huge advantage for patients is that vaginal probiotics have no reported adverse side effects23 38 39, present minimal discomfort37 [Antonio 2009], and can be self-administered23.
Ecologic® FEMI+ Medical Device, for improving the disbalance in the vaginal microbiome
Winclove has developed a probiotic Medical Device for vaginal use: Ecologic® FEMI+. This vaginal capsule aims to improve the natural vaginal microbiome by preventing or improving the disbalance in the microbiome, inhibiting the growing of pathogens and/or preventing the recurrence of vaginal infections.
Selection of strains of Ecologic® FEMI+
The research formulation of the medical device Ecologic® FEMI+ contains a combination of six different bacteria and lactoferrin, an iron-binding protein well known for its anti-candida activity. Pre-clinical data demonstrate that the bacterial strains in Ecologic® FEMI+ are able to produce hydrogen peroxide, D- and L-lactic acid, inhibit the growth of urogenital pathogens, including C. albicans and Candida glabrata, and can survive high concentrations of common antimicrobial and antimycotic drugs.
The selected strain combination from the Ecologic® Femi+ formulation:
- Bifidobacterium bifidum W28
- Lactobacillus acidophilus W70
- Lactobacilus helveticus W74
- Lactobacillus plantarum W21
- Lactobacillus brevis W63
- Lactobacillus salivarius W24
Preclinical and clinical evidence
The bacterial strains in Ecologic® FEMI+ are able to produce hydrogen peroxide, D- and L-lactic acid, inhibit the growth of urogenital pathogens, including C. albicans and Candida glabrata, and can survive high concentrations of common antimicrobial and antimycotic drugs. Furthermore, the bacterial strains in Ecologic® FEMI+ were also shown to adhere strongly to and prevent C. albicans from forming the virulent hyphae morphology in addition to reducing the number of pre-formed hyphae. Equally important, a reduction in the number of adhering hyphae was noted in the presence of compounds produced by the probiotics and this also prevented C. albicans biofilm formation. From the preclinical data, it can be concluded that Ecologic® FEMI+ shows promising evidence regarding mechanisms that can be effective against certain important C. albicans virulence factors.
Winclove Probiotics is further exploring options for a clinical trial in VCI patients. Additionally, Ecologic® FEMI+ is currently being tested in pilot clinical trial in 60 bacterial vaginosis patients.
The research formulation of the medical device Ecologic® FEMI+ is not sold as a consumer product. However our worldwide business partners offer the formulation of the medical device Ecologic® FEMI+ as their own branded product. Thus the specific bacterial composition can be found in different products around the world.
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