Education > Article > Tending to Our ‘Mycobiome’ – Vaginal and Beyond

Tending to Our ‘Mycobiome’ – Vaginal and Beyond

Intimate health issues are without doubt one of the most prevalent, yet under-discussed health complaints facing our society. This article highlights the latest research showing the potential of probiotic yeast for regaining control of vulvovaginal candidiasis (VVC) - also known as thrush - so you have more options in your ‘toolkit'.

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Intimate health issues are without doubt one of the most prevalent, yet under-discussed health complaints facing our society. For far too long they have been cloaked in taboo and shame. Thankfully, the conversation is growing due to the wealth of exciting research in this area, particularly into the therapeutic potential of rebalancing the vaginal microbiome1. This article is intended to help keep the conversation alive by highlighting the latest research showing the potential of probiotic yeast for regaining control of vulvovaginal candidiasis (VVC) – also known as thrush – so you have more options in your ‘toolkit’.

Vulvovaginal Candidiasis (Thrush) – The Problem

VVC is a common fungal infection of the vulva and vagina, which normally presents with a thick, white, curd-like discharge, burning sensation, and possibly an itchy rash. VVC is usually caused by Candida albicans, with a smaller number of cases caused by C. glabrata, C. krusei, and C. tropicalis2, all of which can be tested through vaginal swabs to ascertain the exact nature of vaginal dysbiosis.

Recurrent VVC, defined as four or more episodes of VVC within the last 12 months3, is estimated to affect c. 138 million women worldwide per year and by 2030, this is estimated to increase to c. 158 million4. If left unresolved, which is often due to the high relapse rates, the relentless nature of these gynaecological symptoms can severely impact a woman’s self-confidence, intimate relationships, emotional wellbeing, and quality of life5,6, as well as pregnancy outcomes7. Since VVC is set to become an increasingly frequent clinical encounter, it is important to be aware of recent research developments that have revealed the potential of probiotic yeast for providing sustained relief from VVC8.

The Potential of Yeast-Based Probiotics

The use of probiotics to support vaginal health has been heavily researched in recent years, with a particular focus on lactic acid producing bacteria, namely Lactobacillus spp., given the importance of Lactobacilli dominance in the maintenance of a healthy vaginal ecosystem9. More recently, yeast supplementation has become recognised as a novel therapeutic strategy for vaginal fungal infections10 and in particular, Saccharomyces cerevisiae for VVC. This is timely given growing concern about the ability of Candida to become resistant to conventional anti-fungal interventions11.

Introducing Saccharomyces cerevisiae CNCM I-3856

The promise of Saccharomyces cerevisiae has stemmed from research conducted on the well-characterised strain, Saccharomyces cerevisiae CNCM I-3856 (Quatreflora™ Biotic/Bio.Me™ Femme C). A 2017 randomised, double-blind, placebo-controlled pilot study aimed to investigate whether it could improve the efficacy of conventional anti-fungal protocols for diagnosed VVC. The participants randomised to receive the yeast alongside conventional interventions were given a total daily oral dosage of 2.5 billion CFU, which equates to 500mg, for two months. By the end of the two-month study period, the yeast group had a significantly reduced vaginal load of Candida albicans in contrast to the group taking a placebo alongside conventional intervention. Better still, it achieved this quickly, by the end of the first week. In turn, it helped to reduce the recurrence of VVC too. At the end of the two months, 67% of the subjects taking a placebo experienced at least one VVC relapse symptom, in contrast to only 31% of the subjects taking yeast supplementation. Thus, the yeast/conventional intervention was efficacious and fast-acting. It was also well-tolerated with a high rate of compliance, likely due to the ease and convenience of taking just one capsule a day, orally12. This indicates that it could be a sustainable long-term option for keeping recurrent VVC at bay.

A subsequent randomised, double-blind, placebo-controlled human clinical trial, published this year, has taken our understanding further. They sought to bridge the gap between oral ingestion of Saccharomyces cerevisiae CNCM I-3856 and improved VVC symptoms by checking that this strain reaches the vagina after transit through the gut. They compared a daily dose of 2.5 billion/500mg, 5 billion/1000mg Saccharomyces cerevisiae CNCM I-3856, and placebo, and used the latest identification technology (quantitative polymerase chain reaction/qPCR) to detect the strain in vaginal and stool samples. After four weeks’ supplementation, it was detected in vaginal samples of 21% women in the 500mg group and 16% women in the 1000mg group, making it the first clinical study to identify the migration of orally supplemented probiotic yeasts from the gut to the vagina13.

So, once Saccharomyces cerevisiae has reached the vagina, how does it go on to benefit vaginal health? Various mechanisms have been suggested based upon preliminary in vitro and animal studies. It seems to act directly on the vaginal microbiome by improving the host-vaginal microbiome relationship:

Host: reduces recruitment of inflammatory mediators to the vagina, such as interleukin-8 (IL-8), particularly when administered vaginally (14).

Microbiome: suppresses the ability of C. albicans’ transition from yeast to hyphal form, its production of virulence factors, and its adherence to vaginal epithelial cells (15). It might even help to stave off Gardnerella vaginalis, a common driver of bacterial vaginosis16, indicating wider benefits for the vaginal ecosystem.

S. cerevisiae CNCM I-3856 & the Gut & Oral Microbiota

Saccharomyces cerevisiae CNCM I-3856 may benefit multiple microbiomes, beyond the vagina. A benefit for gut health was demonstrated recently by a study which showed that 2 billion CFU twice daily, taken orally for 8 weeks can improve IBS symptoms17, while a murine study has indicated its potential to decrease C. albicans in the oral cavity18. Given the interconnectedness of our oral, gastrointestinal, and vaginal microbiota, the potential of this probiotic yeast to positively modulate each of them is highly promising!

Clinical Considerations

We need to look at our bodies less as battlefields to be conquered, and more as gardens to be tended.
Martin Blaser, ND

Given the burden of recurrent VVC on the lives of so many women, the latest research showing the potential of Saccharomyces cerevisiae CNCM I-3856 to exert marked, sustainable benefits to vaginal health makes it an essential addition to our therapeutic toolbox. As it has been shown to improve the efficacy of prescribed conventional anti-fungal interventions, it might even help to foster an inter-disciplinary dialogue about VVC which, I think we would all agree, is the future. The inclusion of this probiotic yeast, alongside additional holistic interventions to support the host-microbiome relationship, such as vitamin A, D, and zinc for mucosal integrity19, polyphenols for their prebiotic and anti-inflammatory properties20, and vagina-specific Lactobacilli probiotics (e.g. L. plantarum, L. gasseri, L. crispatus) to further support the resilience of the vaginal ecosystem to stave off pathogens21,22, holds great promise for helping women to finally get on top of their vaginal health issues and live their lives to the full.

References
  1. García-Velasco JA, Menabrito M, Catalán IB. What fertility specialists should know about the vaginal microbiome: a review. Reprod Biomed Online [Internet]. 2017;35(1):103–12. Available from: http://dx.doi.org/10.1016/j.rbmo.2017.04.005
  2. obel JD. Vulvovaginal candidosis. Lancet (London, England) [Internet]. 2007 Jun 9 [cited 2019 Apr 17];369(9577):1961–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17560449
  3. van Schalkwyk J, Yudin MH, Allen V, Bouchard C, Boucher M, Boucoiran I, et al. Vulvovaginitis: Screening for and Management of Trichomoniasis, Vulvovaginal Candidiasis, and Bacterial Vaginosis. J Obstet Gynaecol Canada [Internet]. 2015 [cited 2020 Nov 26];37(3):266–74. Available from: https://pubmed.ncbi.nlm.nih.gov/26001874/
  4. Denning DW, Kneale M, Sobel JD, Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: a systematic review [Internet]. Vol. 18, The Lancet Infectious Diseases. Lancet Publishing Group; 2018 [cited 2020 Nov 26]. p. e339–47. Available from: https://pubmed.ncbi.nlm.nih.gov/30078662/
  5. Moshfeghy Z, Tahari S, Janghorban R, Najib FS, Mani A, Sayadi M. Association of sexual function and psychological symptoms including depression, anxiety and stress in women with recurrent vulvovaginal candidiasis. J Turkish Ger Gynecol Assoc [Internet]. 2020 [cited 2020 Nov 26];21(2):90–6. Available from: https://pubmed.ncbi.nlm.nih.gov/31640303/
  6. Fukazawa EI, Witkin SS, Robial R, Vinagre JG, Baracat EC, Linhares IM. Influence of recurrent vulvovaginal candidiasis on quality of life issues. Arch Gynecol Obstet [Internet]. 2019 [cited 2020 Nov 26];300(3). Available from: https://pubmed.ncbi.nlm.nih.gov/31270690/
  7. Holzer I, Farr A, Kiss H, Hagmann M, Petricevic L. The colonization with Candida species is more harmful in the second trimester of pregnancy. Arch Gynecol Obstet [Internet]. 2017 Apr 1 [cited 2020 Nov 26];295(4):891–5. Available from: https://link.springer.com/article/10.1007/s00404-017-4331-y
  8. Willems HME, Ahmed SS, Liu J, Xu Z, Peters BM. Vulvovaginal Candidiasis: A Current Understanding and Burning Questions. J Fungi [Internet]. 2020 Feb 25 [cited 2020 Nov 26];6(1):27.
  9. Matsubara VH, Bandara HMHN, Mayer MPA, Samaranayake LP. Probiotics as Antifungals in Mucosal Candidiasis. Clin Infect Dis [Internet]. 2016 May 1 [cited 2020 Nov 26];62(9):1143–53. Available from: https://academic.oup.com/cid/article/62/9/1143/1745140
  10. Gaziano R, Sabbatini S, Roselletti E, Perito S, Monari C. Saccharomyces cerevisiae-Based Probiotics as Novel Antimicrobial Agents to Prevent and Treat Vaginal Infections. Front Microbiol. 2020;11(April):1–7.
  11. Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS. Mechanisms of antifungal drug resistance. Cold Spring Harb Perspect Med [Internet]. 2015 Jul 1 [cited 2020 Nov 26];5(7). Available from: /pmc/articles/PMC4484955/?report=abstract
  12. Cayzeele-decherf A, Pélerin F, Jüsten P. Saccharomyces cerevisiae CNCM I-3856 as a Natural Breakthrough for Vaginal Health : A Clinical Study. Med J Obs Gynecol. 2017;5(4):1112.
  13. Decherf A, Dehay E, Boyer M, Clément-Ziza M, Rodriguez B, Legrain-Raspaud S. Recovery of saccharomyces cerevisiae CNCM i-3856 in vaginal samples of healthy women after oral administration. Nutrients [Internet]. 2020 Aug 1 [cited 2020 Nov 26];12(8):1–16. Available from: https://pubmed.ncbi.nlm.nih.gov/32722250/
  14. Gabrielli E, Pericolini E, Ballet N, Roselletti E, Sabbatini S, Mosci P, et al. Saccharomyces cerevisiae-based probiotic as novel anti-fungal and anti-inflammatory agent for therapy of vaginal candidiasis. Benef Microbes. 2018;9(2):219–30.
  15. Pericolini E, Gabrielli E, Ballet N, Sabbatini S, Roselletti E, Cayzeele Decherf A, et al. Therapeutic activity of a Saccharomyces cerevisiae-based probiotic and inactivated whole yeast on vaginal candidiasis. Virulence [Internet]. 2017;8(1):74–90. Available from: http://dx.doi.org/10.1080/21505594.2016.1213937
  16. Sabbatini S, Monari C, Ballet N, Mosci P, Decherf AC, Pélerin F, et al. Saccharomyces cerevisiae–based probiotic as novel anti-microbial agent for therapy of bacterial vaginosis. Virulence [Internet]. 2018 Jan 1 [cited 2020 Nov 26];9(1):954–66. Available from: /pmc/articles/PMC6037478/?report=abstract
  17. Gayathri R, Aruna T, Malar S, Shilpa B, Dhanasekar KR. Efficacy of Saccharomyces cerevisiae CNCM I-3856 as an add-on therapy for irritable bowel syndrome. Int J Colorectal Dis. 2020;35(1):139–45.
  18. Roselletti E, Sabbatini S, Ballet N, Perito S, Pericolini E, Blasi E, et al. Saccharomyces cerevisiae CNCM I-3856 as a new therapeutic agent against oropharyngeal candidiasis. Front Microbiol. 2019;10(JULY).
  19. Cantorna MT, Snyder L, Arora J. Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis. Crit Rev Microbiol [Internet]. 2018 [cited 2020 Mar 20];54(2):184–12. Available from: https://www.tandfonline.com/action/journalInformation?journalCode=ibmg20
  20. Cardona F, Andrés-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuño MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013 Aug;24(8):1415–22.
  21. Murina F, Vicariotto F. Evaluation of an Orally Administered Multistrain Probiotic Supplement in Reducing Recurrences Rate of Bacterial Vaginosis: A Clinical and Microbiological Study. Adv Infect Dis. 2019;09(03):151–61.
  22. Mezzasalma V, Manfrini E, Ferri E, Boccarusso M, Di Gennaro P, Schiano I, et al. Orally administered multispecies probiotic formulations to prevent uro-genital infections: a randomized placebo-controlled pilot study. Arch Gynecol Obstet. 2017;295(1):163–72.

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