The human host is perpetually struggling with the need to tolerate and harbor beneficial microorganisms, while at the same time being able to recognize and eliminate similar microorganisms that are pathogenic. Such sophisticated and intricate system is thought to be shaped in early life via exposure to several key microorganisms.

Thorough research in recent decades has established that the microorganisms inhabiting the vagina (i.e. healthy vaginal microbiome) represent a first line of defense in the female genital tract. Consequently, women deficient in vaginal Lactobacillus species are at an increased risk for serious reproductive diseases and unfortunate obstetric outcomes, but are also more prone to the acquisition of various sexually transmitted infections and the development of pelvic inflammatory disease.

Sexually transmitted infections are transmitted primarily by means of human sexual behavior; therefore, they represent a significant public health issue (especially in developing countries). These diseases have plagued humans for millennia, and they may give rise to chronic diseases, infertility, pregnancy complications, and sometimes even death.

Abnormal Vaginal Flora and Sexually-Transmitted Infections

The cervico-vaginal mucosa is a portal of entry for a myriad of pathogenic microorganisms in women, which results in infections localized at the genital level. Although the exact details of protection generated by a healthy vaginal ecosystem against sexually transmitted infections is still an area of active research, it seems the major factors that affect the risk are lower numbers of lactic acid–producing bacteria (lactobacilli), local cytokine production and high vaginal pH.

Several studies have shown that abnormal vaginal flora can be linked to the acquisition of gonorrhea, chlamydia and trichomoniasis. Also, many viral sexually transmitted infections (most notably human immunodeficiency virus or HIV, but also human papillomavirus, herpes simplex virus and cytomegalovirus) are associated with the composition of vaginal microbiome.
 

The inverse association between colonization with vaginal lactobacilli and the risk of acquiring gonorrhea infection may be a result of antimicrobial features of Lactobacillus species, harsh competitiveness for nutrients in the vagina, as well as diminished susceptibility in the host. Laboratory studies have demonstrated that all lactobacilli have the ability to inhibit the growth of Neisseria gonorrhoeae (i.e. the causative agent of gonorrhea) if the pH is low enough.

A similar inverse association has been shown by cross-sectional studies for Chlamydia trachomatis and Trichomonas vaginalis as well, while hydrogen peroxide-producing isolates of lactobacilli are inversely associated with the isolation of Ureaplasma urealyticum and Mycoplasma hominis.

The vaginal microbiome is increasingly implicated in the control of latent infection with human papillomavirus (HPV), defense against initial HPV acquisition, as well as increased clearance of this virus. Furthermore, the antiviral activity of lactobacilli when herpes simplex virus binds to the cells is strain-dependent and directly related to the specific adhesion propensity of Lactobacillus strains.

Lactobacilli Colonization and HIV

Statistical models and projections indicate that approximately 30% of new cases of HIV could be prevented if resilient, lactic acid-producing Lactobacillus species predominated in the vaginal microbiome. A paucity of these bacteria often result in the diagnosis of bacterial vaginosis, which is a recurrent, symptomatic, polymicrobial condition and the most frequent vaginal disorder in reproductive-aged women.

A recent study has also shown a four-time higher incidence of HIV-acquisition among women that harbor diverse bacterial communities of anaerobic bacteria in their vaginal microbiome, when compared to women with microbiomes dominated by lactobacilli. This increased risk was completely independent of other factors, such as concomitant presence of other bacteria or viruses, sexual behavior, and condom usage.

When discussing HIV prevention, studies have shown that any type of lactobacilli is considered beneficial, albeit strains that produce hydrogen peroxide provide the most benefit. However, it remains to be seen whether hydrogen peroxide is the protective substance or it simply represents a surrogate for some other, unidentified protective property of the microorganism.