The Rationale for Probiotics in Female Urogenital Healthcare

Gregor Reid PhD MBA, BSc (Hons); Jeremy Burton PhD; Estelle Devillard PhD

Disclosures
In This Article

Abstract

Urogenital infections are a major reason that women visit their family physician and are referred to gastroenterology, gynecology, urology, and infectious disease specialists. The association between abnormal vaginal microbiota and increased risk for sexually transmitted infections, bladder and vaginal infections per se, and a higher rate of preterm labor indicate the need to better understand and manage urogenital health. The concept of probiotics arose from the realization that humans are inhabited with microbes from birth and that these organisms play a role in preventing disease. Defined as "live microorganisms, which when administered in adequate amounts confer a health benefit on the host," probiotic strains have already been shown to effectively prevent diarrhea and to hold potential in preventing and treating tonsillitis, caries, renal calculi, and respiratory infections. This review provides a rationale for the use of probiotics in maintaining female vaginal and bladder health and as a treatment option for recurrent bacterial vaginosis, urinary tract infection, yeast vaginitis, and sexually transmitted infections. We consider only probiotic strains that fulfill the United Nations/World Health Organization Guidelines for Probiotics in being fully characterized and clinically documented through scientific investigations describing known or presumed mechanisms of action. Although medical practitioners as yet are unable to access these probiotic strains, an awareness of recent and ongoing research for probiotics is important, as results are encouraging. The concept of probiotic therapy is familiar to many consumers and although it has historically lacked credibility in the medical community, perceptions are changing.

Scope of the Problem

It seems astonishing that urogenital tract infections (UTIs) in women are viewed with relative apathy by government health and funding agencies, industry, and many investigative clinicians. Globally, an estimated 1 billion women have bladder or vaginal infections each year,[1] with more recent increases noted in candidiasis in Brazil,[2] bacterial vaginosis (BV) in the United States and Indonesia,[3,4] and HIV in Africa.[5] These acute and chronic urogenital infections can significantly affect quality of life in women, although only a single study has investigated (and confirmed) this important facet.[6] Furthermore, secondary complications, such as increased risk for preterm delivery, arise from persistent infections, such as BV.[7]

Yet, for all the adverse effects on well-being and the massive expenditure burden,[8] therapeutic approaches to treatment and prevention of urogenital infections have remained essentially unchanged for many years. Antibiotics and antifungals remain the mainstay of therapy, despite their well-documented side effects ranging from diarrhea, depression, and headaches to renal failure and superinfections. Moreover, these therapies are becoming less effective as a result of antimicrobial resistance[9,10]; in the case of pregnancy, antibiotics may[11] or may not[12] prevent preterm birth even once BV has been "cured."

Most cases of BV, UTI, and yeast vaginitis arise from the host's gastrointestinal tract, as microbes ascend 4 to 5 cm from the anus, thereby showing that the intestine and urogenital tracts are "linked" and that intestinal health can influence the vagina and bladder. Every 15 seconds, a child somewhere in the world dies of diarrheal disease, and up to 60 billion cases of gastrointestinal illness occur every year.[13] The approach of boosting the commensal microbial defenses of the host using probiotic organisms thus has consequences for the gut as well as the vagina.

Bacterial Vaginosis -- Prevalent, Often Misdiagnosed, and Invariably Recurrent

The prevalence of BV varies in different parts of the world—for example, 15% in rural Brazil[14]; 25% in a group of healthy, white, Canadian women[15]; 27.4% in Chicago[16]; and 29.9% in Indonesia[17] to 85% in some prostitute populations.[18] Such factors as vaginal douching[19]; black ethnicity; and low socioeconomic status increase the risk for BV.[20] In addition, the higher rate of BV among black women[21] raises the question of whether host-cell receptor density, diet, or other factors play a role in altering the vaginal microbiota and thereby increasing risk for infection.

Most women are not aware that they have BV. Self-use diagnostic kits are available but are not yet very sensitive or specific.[22] A longitudinal study of women in the United Kingdom showed that at any given time during the menstrual cycle, the vaginal microbiota may be "abnormal."[23] When symptoms of pain, discharge, and itching occur, many women diagnose these symptoms as yeast infections and self-treat with over-the-counter antifungals, when in fact they have BV.[24,25,26] This misdiagnosis and mistreatment can result in adverse consequences.[25] Antimicrobial treatment for BV is suboptimal, with some cure rates as low as 60% 1 month after treatment, and subsequent overgrowth of pathogenic bacteria in the vagina often occurs.[27,28,29]

The common asymptomatic nature of BV has raised the question of whether the condition is actually detrimental to the host. Although specific studies have not been designed to answer this question, the major causes of BV--namely anaerobic or aerobic organisms such as Gardnerella, Prevotella, and Escherichia coli--have all been found to produce virulence factors.[30,31,32]

Association Between an Abnormal Vaginal Microbiota and the Spread of HIV in Women

Women are the fastest-growing HIV-infected population; worldwide, approximately 50% of adults with AIDS are women. According to 2001 data, the proportion of women between 15 and 24 years of age living with HIV/AIDS is 62% worldwide (and 67% in sub-Saharan Africa).[33] Factors contributing to greater transmission among women and girls include lack of access to health information, lack of negotiation power over sexual encounters, rape, dependence on men for housing and income, diminished educational opportunities, low male use of condoms, and young age at first intercourse (12 to 14 years). Studies have also shown that the absence or depletion of lactobacilli in the vagina associated with overgrowth of anaerobic pathogens causing BV results in significantly increased risk for HIV (as well as gonorrhea, chlamydia, and herpes simplex virus infections).[34,35,36,37,38] By mechanisms not yet understood, BV displaces lactobacilli, elevating vaginal pH[39] and creating an environment within which the pathogens survive and can infect the host.

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