Say the word “probiotic” and people think, “gastrointestinal health.” That’s natural, since probiotics are invaluable in the management of digestive system problems. But they are also helpful for other health challenges, including infections of the female urogenital tract, like bacterial vaginosis, vulvovaginal candidiasis and related problems.

This should not come as a huge surprise. Although the vaginal tract is not internally connected to the alimentary canal, the two are intimately related. Bacteria that pass through the digestive system can ascend via the perineum to the vagina. It’s totally reasonable to expect that what promotes GI health would also have relevance for urogenital health.

But while the intestinal and vaginal microbiota are similar, they are not the same. Simply restoring and maintaining healthy gut flora may not be enough to ensure urogenital health.

Vaginal Microbiota: What Is It?

Healthy vaginal microbiota consists of large numbers of lactobacilli (gram-positive rods), small numbers of gram-negative rods, and gram-positive coccobacilli. A milliliter of vaginal fluid contains, on average, around 100 million organisms from 5–10 species, 95% of which are lactobacilli (Anukam KC, et al. Sex Transm Dis. 2006; 33(1): 59–62).

Vaginal flora are surprisingly similar in women around the globe, indicating that these commensal relationships were established long ago and have remained robust over time. From an evolutionary perspective, this suggests an adaptive advantage for both the bacteria and the women: the bacteria get a warm, moist place to live; the women gain protection against vaginal pathogens.

Microbiologists have long held that lactobacilli promote vaginal health by helping to maintain an acidic vaginal pH through production of lactic acid. The logic seems sound: vaginal infections are characterized by elevated vaginal pH and decreased numbers of lactobacilli, ergo lactic acid-producing lactobacilli likely prevent infection by maintaining a low vaginal pH. This rationale is behind the common recommendation that women eat yogurt: the lactobacilli, particularly L. acidophilus, and other “active cultures” should promote vaginal health.

Poking under the hood of this theory led to some interesting observations. It turns out that the interaction between vaginal microorganisms is complex and depends on more than just pH. This came to light when researchers found healthy women who seemed to lack lactobacilli. If large numbers of lactobacilli were necessary to regulate vaginal pH and inhibit pathogens, why were these women healthy?

It turns out that they weren’t entirely devoid of lactobacilli, but those organisms only made up a minute, almost inconsequential portion of the vaginal flora. Something else besides the presence of large numbers of lactic acid-producing bacteria was involved in maintenance of vaginal health.

Lactic acid does play a role, but it seems that a critical factor is the presence of strains that produce bacteriocins and other specific regulating factors that inhibit adhesion, growth, and survival of undesirable organisms. Such specific factors can have prominent effects even at very low concentrations. Strains that produce them can be present in tiny amounts while still having a large effect.

Bacterial Vaginosis: Under the Radar

Bacterial vaginosis (BV) is the most common vaginal infection, affecting roughly 10–29% of the female population (Allsworth JE, Peipert JF. Obstetr Gynecol. 2007; 109: 114–120). BV is the primary reason for more than 4 million office visits per year in the US (Van Kessel K, et al. Obstet Gynecol Surv. 2003; 58: 351–358). Yet despite these numbers, researchers believe many cases still go untreated or mistreated.

BV is characterized by a shift in the vaginal microbiota from predominantly commensal organisms like lactobacilli, to pathogens such as species of Gardnerella, Atopobium and Prevotella. Some of these organisms produce amines that raise the pH in the vagina and cause a “fishy” smell.

The symptoms of BV are somewhat similar to those of a yeast infection. Since this is a sensitive, even embarrassing topic, and because over-the-counter anti-fungals are readily available, many women try to self-treat BV with anti-yeast remedies. Unfortunately, these won’t help, and often make the situation worse.

Be aware that levels of lactobacilli tend to track with estrogen levels, meaning that even women who seem healthy may be at increased risk of BV when estrogen is low, like at the beginning and end of the menstrual cycle, or after going into menopause.

BV, Preterm Labor & STDs

On face value BV may seem more like an annoyance than a serious medical condition. This is a fallacious and short-sighted view. BV can lead to extensive local inflammation and increased susceptibility to sexually transmitted infections.

It has been associated with increased incidence of HIV, cytomegalovirus, chlamydia gonorrhea and pelvic inflammatory disease (Anukam KC, et al. Sex Transm Dis. 2006; 33(1): 59–62. Sewankambo N, et al. Lancet. 1997; 350: 546–550. Ross SA, et al. J Infect Dis. 2005; 192(10): 1727–1730. Nilsson U, et al. Sex Transm Dis. 1997; 24(5): 241–246. Joesoef MR, et al. Int J STD AIDS. 1996; 7(1): 61–64. Brotman RM, et al. J Pediatr Adolesc Gynecol. 2007; 20(4): 225–231).

None of these studies prove a definitive causal relationship between BV and STDs, but the strength of the correlations warrants serious clinical scrutiny.

BV is also linked with a heightened risk of preterm labor. In the US, 7–10% of all babies are delivered preterm, and the number has risen steadily over the last 10 years. Women at risk for preterm labor cost the healthcare system roughly $360 million annually.

We’ve known for some time that there is a correlation between BV in an expectant mother and preterm delivery (Hillier SL, et al. Obstet Gynecol. 1992; 79(3): 369–373. Chaim W, et al. Arch Gynecol Obstet. 1997; 259: 51–58. Purwar M, et al. J Obstet Gynaecol Res. 2001; 27(4): 175–181).

Pregnant women are frequently treated with antibiotics to fend off group B streptococci and also as a precautionary measure when the amniotic sac ruptures prematurely. But this increased use of antibiotics means more frequent assaults on the vaginal microbiota and a greater overall risk of BV. Antibiotics used to treat BV or other conditions can cause complications during pregnancy and severely disrupt the vaginal microbiota, thus facilitating future BV episodes.

This is problematic not only for the mother but also for the baby, because transmission of endogenous bacteria from mother to newborn occurs during birth, helping to establish the newborn’s own gut flora and immune system. Disruption of the maternal flora by antibiotic therapy interferes with this process.

Clearly, antibiotics treatment for pregnant women has drawbacks. Some researchers have suggested that orally administered probiotics specially formulated for vaginal health could help eliminate the conditions that cause preterm labor and hence avoid many of these problems (Reid G, Bocking A. Am J Obstet Gynecol. 2003; 189: 1202–1208).

An Ounce of Prevention

Given the short external distance between the anus and the vagina, and the fact organisms naturally migrate across the perineum, it stands to reason that a healthy urogenital environment begins with healthy GI flora. The healthier the intestinal microbiota, the lower the odds that disruptive organisms will pass from the digestive tract to the vagina.

Beneficial intestinal microbiota are more apt to flourish on a diet high in fiber (especially prebiotic fibers) and low in simple sugars and refined carbohydrates. In contrast, pathogenic bacteria tend to outpace friendly ones when the diet is high in simple sugars and low-fiber processed foods.

Eating yogurt with live active cultures may help, although the clinical evidence to support this is somewhat equivocal. Digestive health may be better served by taking a probiotic supplement that contains multiple strains clinically documented to support gut health.

Women may be able to prevent BV with probiotic products specifically formulated and tested for vaginal health. Ideally, these should contain strains originally isolated from a healthy woman and well characterized to act against vaginal pathogens. Two strains that actually meet those standards are: Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Used together, these have been shown to promote healthy vaginal microbiota (see “Research Review”).

Probiotics & BV Treatment

Standard treatment for bacterial vaginosis involves oral or intravaginal antibiotic drugs. The most common agents are metronidazole or clindamycin for one week. Intravaginal treatments include metronidazole gel or 2% clindamycin cream applied daily for a week. Regardless of which antibiotic is used, statistics show that roughly 30% of BV infections recur within one month and approximately 80% within 9 months. Also be aware that local use of clindamycin is contraindicated for pregnant women because of a possible connection to birth defects.

Many physicians will recommend probiotics following antibiotic therapy, to bolster beneficial GI bacteria killed off during treatment. The same advice applies to the urogenital tract: the vaginal commensals are just as susceptible to broad-spectrum antibiotics as the ones in the intestines.

Although there is not yet any solid evidence that probiotic monotherapy is effective against existing BV infections, probiotic supplementation can provide dividends before, during and after antibiotics Some probiotic strains can even improve the efficacy of antibiotics (see “Research Review”).

Vulvovaginal Candidiasis: Bacteria vs. Yeast

About 75% of women have vulvovaginal candidiasis (VVC), aka “yeast infection,” during their lives. BV and other disruptions of bacterial microbiota make VVC more common, recurrences more likely, and outbreaks more difficult to treat.

Various species of Candida are present in a healthy vaginal environment, but at very low levels. VVC is an over-proliferation of Candida, with C. albicans accounting for 85–90% of cases. A Candida bloom causes inflammation and can lead to vaginal discharge and irritation. VVC is characterized by a thick, whitish, non-uniform discharge that does not typically possess a “fishy” odor. Irritation during sexual intercourse and itchiness of the vagina and surrounding area are common. One can easily see the Candidal hyphae via microscopic examination of a vaginal smear treated with 10% KOH.

Maintenance of healthy urogenital microbiota decreases the risk of VVC. Prophylactic probiotic use is one way to support the healthy bacterial flora that can inhibit uncontrolled growth of yeast (Reid G, et al. FEMS Immunology and Medical Microbiology. 2003; 35: 131–134).

Oral antifungals like fluconazole, daily for two weeks, are the standard first-line drug treatment for VVC. Prescription and OTC antifungal creams and pessaries are also commonly used. But keep in mind that these treatments can inhibit not only the fungi, but also the endogenous lactobacilli in the vagina, predisposing a woman to repeated Candidal overgrowth.

There are several published reports showing that standard antifungal drug treatment in combination with a vaginal probiotic containing L. rhamnosus GR-1/L. reuteri RC-14 significantly reduces symptoms of yeast infection as compared to standard drug treatment alone (see “Research Review”).

The key to understanding urogenital health is to realize that it is not about the absence of bacteria, but rather the presence of the right organisms in the proper balance. Probiotic strains that have been shown to support urogenital health are an excellent option for promoting a balanced urogenital microbiota and preventing infection.

This deserves serious consideration, since drug treatments for vaginal infections are of limited efficacy, especially for recurrent infections. Urogenital probiotics can also be a helpful adjuvant to standard treatment in many cases, helping mitigate side effects and in some cases bolstering treatment efficacy. Women are often very relieved to learn that there is more they could be doing to prevent and treat troublesome vaginal infections. Make sure to tell them!

Brad Douglass, PhD is a Technical Specialist for Jarrow Formulas. He obtained his PhD from USC in Organic Chemistry where his research efforts concentrated on drug discovery. He was also a postdoctoral fellow at USC where he investigated novel blood-brain barrier transport methods for use in drug delivery to the brain.

Urogenital Probiotics: A Research Review

A number of published studies and case reports show the value of probiotics in preventing and treating vaginal infections and other urogenital problems in women. Here are a few key papers:

Effects on Urogenital Microbiota

Forty-two clinically healthy women were randomized into four groups: three active treatment groups that received various oral dosages of an L. rhamnosus GR-1/L. reuteri RC-14 (GR-1/RC-14) probiotic supplement, and a control group receiving L. rhamnosus GG every day for 28 days. All three treatment groups saw a significant increase in healthy vaginal microbiota, while the control group showed no change. The twice-daily treatment group accrued the most benefit, with 90% of patients showing normal vaginal microbiota two weeks after treatment. The study suggests that a daily dose of about 1 billion (10⁹) live GR-1/RC-14 organisms is adequate as a preventative regimen (Reid G, et al. FEMS Immunol Med Microbiol. 2001; 32: 37–41).

Lactobacilli, Yeast & Coliforms

	Fig. 1. Average (Log) Difference in Microbiota Populations After 1 Month Daily Use.
	Fig. 2. Effectiveness of Metronidazole + GR-1/ RC-14 Probiotic for BV.

Sixty-four healthy women were randomized to receive either a once-daily oral GR-1/RC-14 supplement for 60 days, or a calcium carbonate placebo. Microscopic analysis on Day 28 showed that the treatment group had an almost 10-fold increase in lactobacilli over baseline, while the placebo group showed a lactobacillus decline. The placebo patients also showed a significantly greater presence of yeast and coliform bacteria (Fig. 1) (Reid G, et al. Clin Ther. 1992; 14(1): 11–16).

Bacterial Vaginosis Prevention

In the previous study, blinded observers used Nugent scoring to assess the development of BV. Of those possessing a healthy vaginal microbiota at the outset, none of the women on the GR-1/RC-14 probiotic (0/23), but 24% (6/25) of those in the placebo group developed BV by Day 35 (Reid G, et al. Clin Ther. 1992; 14(1): 11–16).

Probiotics Plus Antibiotics for BV

In women with BV, the combination of GR-1/RC-14 probiotic (1 capsule, 10 billion CFUs), twice daily, plus oral metronidazole (500 mg), twice daily, more than doubled (88% response rate) the efficacy of metronidazole alone (40% response) (Fig. 2) (Anukam KC, et al. Microbes and Infection. 2006; 8: 1450–1454).

Preventing Preterm Labor

Thirty pregnant women with BV and at high risk of preterm delivery, were randomized to a once-daily oral GR-1/RC-14 capsule for 15 days, or standard care without any BV treatment. After one month, the treatment group showed decreased indicators of BV. But more importantly, 100% of the mothers in the treatment group delivered at term, as opposed to 67% of the controls. There were no adverse events (Dobrokhotova YE, Sci M. All-Russian Scientific Forum: Mother and Baby. October 2, 2007).

Treating Vulvovaginal Candidiasis

Sixty-eight women with VVC were randomized to either fluconazole, 150 mg/day plus 2 capsules of GR-1/RC-14 (10 billion organisms), once daily, or fluconazole plus placebo. After 28 days, the treatment group showed more than a three-fold decrease in yeast levels and vaginal discharge compared to the control group (Martinez RC, et al. Lett Appl Microbiol. 2009; 48(3): 269–274).

Preventing Urinary Tract Infections

Reid and colleagues compared UTI recurrence rates in 41 women treated with either standard 3-day antibiotics alone or antibiotics followed by a GR-1 probiotic. They first treated the women with either norfloxacin or co-trimazole (the UK name for trimethoprim-sulfamethoxazole, and not to be confused with the antifungal, clotrimazole). Recurrence rates were 29% in the norfloxacin group and 41% for those on co-trimazole. Afterward all women were then randomized to either a GR-1 probiotic suppository or sterilized skim milk as a pessary, twice a week for two weeks, with two additional instillations at 4 weeks and 8 weeks. The GR-1 group had a recurrence rate of 21% over the ensuing 6 months; for the skim milk group it was 47% (Reid et al. 1992). In another randomized trial, a weekly GR-1 combination probiotic (10 billion CFUs) was given as a pessary for one year. This decreased UTIs from a mean of 6 infections in the year prior to the study, to only 1.6 per year during the study (Reid G, Bruce AW, Taylor M. Microecology Therapy. 1995; 23: 32–45).