PROBIOTICS AND THEIR ROLE IN VAGINAL HEALTH
1. What are probiotics? What does the term even mean?
Probiotics, specific health-promoting microbes, have multifactorial benefits to human health and some may have been part of daily diet for centuries in the form of traditional fermented foods or beverages.
Typically, these products will contain freeze-dried (lyophilized) or live bacteria or yeasts, most commonly from the genera Lactobacillus and Bifidobacterium.
The original definitions of probiotics were inclusive of traditional fermented foods such as yogurt (nonmedicinal varieties), sauerkraut, and kefir, but the most recent interpretation of the definition has, somewhat controversially, excluded these traditional ferments. These are now considered food sources of โlive and active culturesโ but not probiotics.
2. How do they work?
Probiotics may exert their beneficial effects in various settings by different mechanisms.
These include:
– production of antimicrobial factors such as bacteriocins,
– making it difficult for the bad microbes to bind to the lining by competing for the surface
– competing for nutrients
– conditioning the inner lining (mucosal epithelium) and tissues just beneath.
– modulation of the immune system (T -cell proliferation)
– They can also send molecular signals to the host (human in this case) body so the body can recognize the good vs bad guys through special receptors called TLRs (toll like receptors) present on the surface of certain cells.
– antimicrobial activity and suppression of bacterial growth
3. Which ones are some common โgoodโ probiotic microbes relevant to vaginal health?
o Lactobacillus acidophilus
o Lactobacillus casei
o Bifidobacterium longum
o Bifidobacterium bifidum
o Lactobacillus ruterii
o Lactobacillus johnsonii
o Bifidobacterium lactis
o Lactobacillus plantarum
4. What is present in a normal healthy vagina?
Normal healthy vagina is a smorgasboard of bacteria, cells, immune cells, debris, secretions and immune antibodies.
5. Does the normal composition of the vaginal microbiome change naturally?
Yes, several factors affect the above composition.
Age, menstruation, estrogen level, smoking, intercourse, hygiene habits and other practices have been shown to significantly impact the VMB composition (Hickey et al., 2012).
During the menstrual cycle the vaginal composition is more stable when estrogen levels are high. Good levels of estrogen support a healthy vaginal environment through increasing the glycogen content in the vaginal epithelial cells. Glycogen, which is a storage form of glucose, has been shown to promote growth of lactobacilli.
6. How is the vaginal microbiome classified?
Due to the complicated nature and a huge variety of different microbial populations, several attempts have been made by researchers to classify or group the organisms. One of the commonly used ones is described below. It classifies the various states of the microbiome as a โcommunity stateโ. These groups or states have been identified through PCR based 16S rRNA sequencing
Five different community state types (CST) were proposed by Ravel et al. (Ravel et al., 2011).
Good (Lactobacilli are the dominant species).
CST I- Lactobacillus crispatus
CST II- Lactobacillus gasseri
CST III- Lactobacillus iners
CST V- Lactobacillus jensenii
CST I and III are the most common.
Women with these Lactobacillus-dominant CSTs also exhibit low vaginal pH (typically < 4.5).
Bad CST IV: less lactobacilli and dominant anaerobic and microaerophilic bacteria.
This state is correlated with higher vaginal pH (> 4.5).
Two subdivisions of CST IV have been identified:
1) CST IV a: some lactobacilli, with some Anaerococcus, Corynebacterium, Finegoldia, or Streptococcus
2) CST IV b: high proportion of Atopobium, with the below microbes:
Prevotella, Parvimonas, Sneathia, Gardnerella, Mobiluncus, Peptoniphilus and other taxa (Gajer et al., 2012). Several bacteria present in the CST IV-B are associated with bacterial vaginosis (BV).
7. Other than hormones and age, what else influences the vaginal microbiome?
Different ethnic groups have been shown to have different CSTs.
The Lactobacillus-dominant CSTs are widely prevalent in Asian and White/Caucasian women (80%โ90%), however only 60%โ70% of African American or Hispanic women have Lactobacillus-dominant CSTs.
8. What are the harmful effects of being in the CST IV state?
– recurrent vaginal infections called Bacterial Vaginosis (BV).
– has been associated with adverse reproductive and obstetric health outcomes
– increased risk of acquiring sexually transmitted infections
– pelvic inflammatory disease, endometritis, preterm birth, and spontaneous abortions (Martin and Marrazzo, 2016).
9. How do lactobacilli keep the vagina healthy?
– lactobacilli produce lactic acid, which acidifies the vaginal microenvironment and provides protection against genital infections.
– lactobacilli also do not allow many pathogens to live in the vaginal environment by competing for resources in the vaginal microenvironment with other microorganisms.
– the protective effect of Lactobacillus-dominant states has also been attributed to hydrogen peroxide.
Overall, Lactobacillus-dominant states are associated with vaginal health, and the disruption of this healthy state leads to a disturbed state of health.
10. How do probiotics help in vaginal health?
To clarify, here we are focusing on the probiotics that include most of the above listed โgoodโ lactobacilli.
Their role in vaginal health has been extensively investigated especially in the context of vaginal infections in premenopausal women (Borges et al., 2014; Petrova et al., 2015).
Increasing evidence shows that specific probiotic strains or their combinations elevate vaginal lactobacilli counts in healthy women or women with BV and/or vulvo-vaginal candidiasis (VVC).
Probiotics also help and support natural health vaginal state during/after recovery from antibiotics/antifungal treatment (Xie et al., 2017; Li et al., 2019).
A meta-analysis that involved 10 RCTs with a low or moderate risk of bias, suggested that the treatment with probiotics alone was more effective in the therapy of BV for both short- and long-term; however, the probiotics used after antibiotic treatment was effective only for a short term.
According to another meta-analysis of 13 studies by Hansen et al, probiotic interventions were effective for treatment and prevention of BV, prevention of recurrences of candidiasis and UTIs, and clearing HPV lesions. No study reported significant adverse events related to the probiotic intervention.
11. So, what happens to the vaginal microbial balance after menopause?
The decline in estrogen levels affect the vaginal health in multiple ways. We wonโt discuss the thinning and lack of lubrication aspect here.
The vaginal pH increases and that can allow growth of harmful microbes such as Escherichia coli, Candida spp., and Gardnerella spp. leading to increased risk of BV and VVC [reviewed by Kim and Park (2017)].
12. How can you build a health vaginal microbiome? Which lactobacilli should you be looking for?
Below are some names and specifications that are required for a healthy community state as described above. So, pay attention to the exact concentration and names of the lactobacilli in your probiotic?
– Lactobacillus rhamnosus GR-1
– Lactobacillus reuteri RC-14
– Lactobacillus crispatus LMG S-29995
– Lactobacillus brevis
– Lactobacillus acidophilus
– Lactobacillus crispatus LbV 88
– Lactobacillus gasseri LbV 150N
– Lactobacillus jensenii LbV 116
– Lactobacillus rhamnosus LbV96
– L. brevis (CD2),
– L. salivarius subsp.salicinius (FV2)
– L. plantarum (FV9)
Among the lactic acid bacteria, L. plantarum attracted many researchers because of its wide applications in the medical field with antioxidant, anticancer, anti-inflammatory, antiproliferative, anti-obesity and antidiabetic properties.
13. How do probiotics help in BV?
There is increasing evidence that probiotics are effective in the treatment of BV. In a meta-analysis of 30 studies (Jeng et al., 2020), BV patients were followed up after treatment and found that probiotic intervention:
– reduced the recurrence rate of vaginitis (OR = 0.27, 95% CI: 0.18-0.41, P<0.001),
– improved the cure rate of vaginitis (OR = 2.28, 95% CI: 1.20-4.32, P = 0.011).
(Selis et al. (2021) proved through in vitro experiments that Lactobacillus plantarum Lp62 could significantly inhibit the growth of Gardnerella.
In another meta-analysis of 18 studies (Liu and Yi, 2022) with 3-month follow-up, the combination of antibiotics and probiotics was found to significantly reduce the recurrence rate of BV compared with antibiotics alone.
L. plantarum can reduce the pathogenicity of G.vaginalis by repressing the expression of the genes related to virulence factors, adhesion, biofilm formation, metabolism, and antimicrobial resistance (Qian et al., 2021).
L. gasseri can reduce viable G. vaginalis numbers, inhibit sialidase activity, regulate TNF-ฮฑ and IL-1ฮฒ expression, and decrease myeloperoxidase activity in experimental mouse models (Zhang et al., 2022).
14. Which route is the best? Vaginal or oral?
This is still a huge field of research. So far, vaginal placement of probiotics has not led to any conclusive benefits. More studies are underway, though!
Through a mechanism that we may call, โgut-vaginaโ axis, oral ingestion of high doses of beneficial lactobacilli has been showed to improve the vaginal microbiome state as discussed above.
One study of 39 patient who received vaginal preparations of 3 different lactobacilli did show an improvement in BV symptoms.
15. Does HPV affect the vaginal microbiome and can probiotics help?
There is some data showing oral Lactobacillus curlicus can change the state of CST and increase HPV clearance.
HPV can destroy the vaginal microecological balance, reduce the number of Lactobacillus and increase the adhesion and colonization of abnormal flora. This can lead to increased expression HPV protein leading to the development of cervical intraepithelial neoplasia (CIN), and even leads to the occurrence of cervical cancer.
Inflammation is considered to be a predisposing factor for tumorigenesis and development.
(Curty et al., 2019). Gao et al. (Gao et al., 2013) were the first to systematically evaluate the relationship between vaginal microbiota and HPV infection and found that vaginal bacterial diversity in HPV-positive women was more complex and the composition of vaginal microbiota was different. A study (DI Pierro et al., 2021) demonstrated for the first time that oral Lactobacillus curlicus can change the state of CST and increase HPV clearance.
16. How can lactoferrin help with BV?
Lactoferrin can act as an immune modulator in situations where low amounts of vaginal lactobacilli and increased levels of endogenous anaerobic bacteria are present.
17. What else can lactobacilli do?
There is some evidence that L. crispatus can decrease the adhesion and invasiveness of N. gonorrhoeae through reducing the expression of genes responsible for pro-inflammatory cytokines like TNF-ฮฑ and CCL20 in N. gonorrhoeae-infected epithelial cells (Pลaczkiewicz et al., 2020).
There is a lot of research on the benefits of lactobacilli in fertility, obesity, metabolic syndrome and weight control, HIV, HPV and HSV infections. We can go into these details another time.
18. Can the probiotics do harm?
Since probiotics contain micro-organisms they can cause infections in susceptible individuals and this can happen in very sick patients.
19. I have been taking probiotics forever, why donโt I have any lactobacilli in my vagina?
Yes, that is indeed the million-dollar question. Multiple factors could be involved. Only some are listed below:
– The bad guys are so determined to be there that you need stronger and long term suppressive regimens while the health bacteria can take over.
– Your bodyโs immune system may be suppressed or under attack through inflammation or autoimmune conditions that are allowing the bad guys to linger.
– Your hormonal balance may be off. See above.
– You may have diabetes or high sugar. Bad guys love sugar and so does inflammation.
– Your lifestyle may not be allowing your vagina to breath.
– You many not be taking the right stuff (see above again) in appropriate quantities and consistently. We recommend multiple strains over atleast 50 billion CFUs twice a day with multiple strains for almost a year until you can see any noticeable changes.
Here is the Plea from you V that can serve as a guide for you!!
Be safe, be strong and be prepared.
Dr. Adeeti Gupta
References:
1. Wang Z, He Y, Zheng Y. Probiotics for the Treatment of Bacterial Vaginosis: A Meta-Analysis. International Journal of Environmental Research and Public Health. 2019; 16(20):3859. https://doi.org/10.3390/ijerph16203859
2.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024219/#:~:text=Increasing%20evidence%20show%20that%20specific,et%20al.%2C%202019).
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7. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/vagina-flora
8. Mei Z, Li D. The role of probiotics in vaginal health. Front Cell Infect Microbiol. 2022 Jul 28;12:963868. doi: 10.3389/fcimb.2022.963868. PMID: 35967876; PMCID: PMC9366906.