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 “live and active cultures” 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 “good” 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 “community state”. 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%–90%), however only 60%–70% 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 “good” 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 won’t 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-α and IL-1β 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, “gut-vagina” 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-α and CCL20 in N. gonorrhoeae-infected epithelial cells (Płaczkiewicz 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 don’t 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 body’s 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).

3. Hanson L, VandeVusse L, Jermé M, Abad CL, Safdar N. Probiotics for Treatment and Prevention of Urogenital Infections in Women: A Systematic Review. J Midwifery Womens Health. 2016 May;61(3):339-55. doi: 10.1111/jmwh.12472. PMID: 27218592.

4. Arasu MV, Al-Dhabi NA, Ilavenil S, Choi KC, Srigopalram S. In vitro importance of probiotic Lactobacillus plantarum related to medical field. Saudi J Biol Sci. 2016 Jan;23(1):S6-S10. doi: 10.1016/j.sjbs.2015.09.022. Epub 2015 Oct 9. PMID: 26858567; PMCID: PMC4705246.

5. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4680-7. doi: 10.1073/pnas.1002611107. Epub 2010 Jun 3. PMID: 20534435; PMCID: PMC3063603.

6. https://ami-journals.onlinelibrary.wiley.com/doi/10.1111/jam.13438

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.

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1. All Vaginal discharge are not infectious.  Recurrent and persistent mixed vaginal infections can now be accurately diagnosed by a vaginal culture which can be performed through the Pap smear test at the same time.

2. Mixed infections with Candida (Yeast) and BV (Bacterial Vaginosis) are more common than you think. 70% of episodes of vaginitis are caused by BV and Yeast.

3. For most women, Vaginitis resolves without any difficulty.

4. Feminine hygiene products, panty liners and douches need to be retired and sent to the land far far away.

5. BV is not an STD! However, partner treatment may help reduce recurrent infections. Long term (6 months) weekly courses of vaginal metronidazole gel after an initial 1 week treatment with oral metronidazole or Tinidazole may be needed if you have recurrent bacterial infections.

6. Your daily chores after a work-out can wait. Excessive sweating, swimming in the pool, hanging out at the beach, wearing tight clothing for long durations can cause vaginal pH imbalance. One needs to hit the shower as soon as possible after a work-out to avoid that irritating BV or Yeast from haunting us.

7. Using mild soaps with no fragrances or irritants is the key. Look for the “water-based” on the label if you use vaginal lubricants!

8. Barrier creams like A&D cream, Aquaphor or the baby diaper rash creams go a long way in preventing chafing and irritation down there.

9. Oral Probiotics supplementation (50 billion CFU daily) in the right amounts daily is the key in healing and preventing recurrent infections.

10. Recurrent Yeast infections may need long term weekly courses of Fluconazole tablets (Need to be prescribed by your OBGYN with caution). Vaginal Boric acid suppositories (compounded by a pharmacist) may help in those persistent infections caused by the resistant yeast.

For more detailed discussion, check out our video series at That’svagenius.

Be safe, be strong and be prepared.

Your friends at Walk In GYN Care

#justwalkin

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Vaginitis is the general term for disorders of the vagina caused by infection, inflammation, or changes in the normal vaginal flora. Symptoms include vaginal discharge, odor, itching, and/or discomfort. These symptoms are extremely common and frequently lead to self-treatment. In a survey of random women in the United States, a healthcare professional was consulted in only 50-80% of the situations and most women purchased an over-the-counter antifungal preparation to treat their symptoms, whether or not they saw a physician.

The vaginal epithelium (or lining) in women of reproductive age is rich in glycogen. Lactobacilli help maintain the vaginal pH between 4.0 to 4.5 (acidic) with the help of strain of lactobacilli called Doderlein’s bacteria. This acidity is needed to maintain the normal vaginal flora and prevent the growth of pathogenic organisms. Disruption of the normal ecosystem can lead to conditions favorable for development of vaginitis. Some of these disruptive factors include phase of the menstrual cycle, sexual activity, contraceptive choice, pregnancy, foreign bodies, estrogen level, sexually transmitted diseases, and use of hygienic products or antibiotics.

Normal discharge may be yellowish, slightly malodorous, and accompanied by mild irritative symptoms. However, if it is not accompanied by itching, pain, burning or significant irritation. Presence of the latter associated symptoms signifies pH imbalance and presence of vaginal infection or vaginitis.

The severity of symptoms correlates with the extent of inflammation. Candida vulvovaginitis (yeast) often presents with marked irritative symptoms such as itching and soreness, but scant discharge (thick, white, odorless, and curd-like). In contrast, Bacterial Vaginosis is associated with only minimal inflammation and minimal irritative symptoms, but the thin, gray or yellow, malodorous discharge is a prominent complaint. Women may complain of a fishy smell or yellowish green discharge. Trichomoniasis is characterized by purulent, malodorous, thin discharge, which may be accompanied by burning, itching, painful urination, frequency, and/or painful intercourse. The vulva also may be affected by candidiasis or yeast infection but not by bacterial vaginosis. Symptoms of candidal vulvovaginitis often occur in the premenstrual period, while symptoms of trichomoniasis often occur during or immediately after the menstrual period.

Vaginal pH — Measurement of vaginal pH is the single most important finding that drives the diagnostic process and should always be determined. A pH test stick (or pH paper if available) is applied for a few seconds to the vaginal sidewall (to avoid contamination by blood, semen, or cervical mucus which pool in the posterior fornix and distort results). Alternatively, the vaginal sidewall can be swabbed with a dry swab and then the swab rolled onto pH paper (if available). The pH of the specimen is stable for about two to five minutes at room temperature. The swab should not be pre-moistened, as the moistening liquid can affect pH.

Narrow range pH paper (4.0 to 5.5) is easier to interpret than broad range paper (4.5 to 7.5). An elevated pH in a premenopausal woman suggests infections such as bacterial vaginosis (pH>4.5) or trichomoniasis (pH 5 to 6), and helps to exclude candida vulvovaginitis (pH 4 to 4.5).

The pH of the normal vaginal secretions in premenopausal women is 4.0 to 4.5 because these women have relatively high estrogen levels. Under the influence of estrogen, the normal vaginal epithelium stabilizes and produces glycogen. In the age groups of women before puberty and after menopause, the pH of the normal vaginal secretions is ≥4.7. The higher pH is due to less glycogen in epithelial cells and reduced lactic acid production. Thus measurement of pH for diagnosis of bacterial vaginosis, trichomoniasis, or candidiasis is less useful at the extremes of age.

Vaginal pH may be altered (usually to a higher pH) by contamination with lubricating gels, semen, douches, and intravaginal medications. In pregnant women, leakage of amniotic fluid raises vaginal pH.

DIAGNOSTIC OPTIONS

Microscopy- Taking a sample of the fluid and examining under the microscope used to be the standard method of evaluation of abnormal vaginal discharge. However, now there are many modern techniques available to accurately diagnose the type of infection to help in the right treatment.

The commercially available tests include rapid antigen and nucleic acid amplification tests are used for confirming the clinical suspicion of bacterial vaginosis or trichomonas vaginitis. The PCR tests can be used for typing and identification of various species of Candida (yeast)

Cervical culture — A diagnosis of cervicitis, typically due to Neisseria Gonorrhea or Chlamydia trachomatis, must always be considered in women with purulent cervical discharge since women with this disorder may go on to develop PID and its potential complications. Any women with new or multiple sexual partners, a symptomatic sexual partner, or an otherwise unexplained cervical or vaginal discharge that contains a high number of white cells should alert the physician for the presence of these organisms, by culture or an alternative sensitive test.

Your health care provider will take a vaginal swab while doing a speculum examination of the vagina. It is like a “pap” exam but the type of swab used by the provider is different. The doctor may also use a pH strip to test the pH of the vaginal secretions to help aid diagnosis. The swab is then sent for testing to the lab via the techniques mentioned above. The results take approximately 3-7 days. The physician may treat if the discharge is highly suggestive and then offer follow up treatment if the cultures show differently.

Difficult diagnosis: Even after a thorough evaluation, 25 to 40 percent of women with genital symptoms may not reveal a specific cause.

Non-infective causes

Irritants and allergens — Vaginal discharge can result from irritants (e.g., scented panty liners, spermicides, povidone-iodine, soaps and perfumes, and some prescription and nonprescription topical medications) and allergens (e.g., latex condoms, topical antifungal agents, seminal fluid, chemical preservatives) that produce acute and chronic hypersensitivity reactions, including contact dermatitis. Women from the developing world may have vaginal practices or use traditional products and medicines that have adverse effects [12].

Diagnosis and management involve identifying and eliminating the offending agent by taking a thorough history and systematically removing potential irritants and allergens from the urogenital environment. Symptom/contact diaries may be helpful.

Estrogen status – Is the woman menopausal or otherwise hypo estrogenic? Atrophic vaginitis is a common cause of vaginitis in hypo estrogenic women. In premenopausal women, hypo estrogenic settings include the postpartum period, lactation, and during administration of antiestrogenic drugs (and sometimes with low estrogen levels related to contraceptives). Menopausal women receiving hormone therapy may not have adequate estrogen levels for vaginal health and thus remain prone to atrophic vaginitis. Nonspecific signs and symptoms include a watery, white or yellow, and malodorous discharge; vaginal burning or irritation; dyspareunia; and urinary symptoms. Physical findings include thinning of the vaginal epithelium, loss of elasticity, pH ≥5 and pain during examination or intercourse.

Treatment outline

• Do not self-treat.
• Do not treat yourself for all possible infections without proper evaluation, culture and diagnosis. The blanket treatment can lead to altering the vaginal pH and lead to either worsening of infection or improper diagnosis and treatment.
• The following information is vital to reaching the root cause of the problem.
• Duration of symptoms, the triggering factors, site of symptoms (vulva versus vagina), recent change in sexual partner, recent intake of oral contraceptives, antibiotics, travel, stress or diagnosis of other medical conditions such as diabetes may play an important role in triggering these conditions.
• Treating the symptoms without delineating the causative factor or agent will not help. The condition will keep recurring and be a source of frustration for both the patient and the health care provider.

Rare causes of persistent vaginal irritation once Candida vaginitis, bacterial vaginosis, and trichomoniasis have been ruled out:

• If pH is increased, non-infectious causes, such as vaginal atrophy, atrophic vaginitis, erosive lichen planus, lichen sclerosus, desquamative inflammatory vaginitis, bacterial vaginosis should be considered.
• If pH is normal, the vagina is likely to be normal with normal bacterial environment, so focus needs to be on the most common vulvar and external causes of vulvovaginal symptoms, such as contact or irritant dermatitis and seborrheic or eczematoid dermatitis etc.
• Group A streptococcal vaginitis is associated with a normal or mildly increased pH, but this is a rare disease.

 Stay tuned for a follow up segment on treatment and prevention of vaginal infections/ itching/ abnormal discharges etc. 

Adeeti Gupta MD, FACOG

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