The vagina is a highly nutrient-rich chamber for microbes that develop into a unique microbiota which has been characterized as complex and diverse. Over time, the vaginal microbiota is a dynamic ecosystem that can determine vaginal health. This ecosystem is mostly bacterial with bacteria usually growing in an environment deprived of oxygen or able to grow in an environment with very low oxygen content 1. In reproductive-aged women, the presence of lactobacilli and their production of lactic acid maintaining a low pH of the vaginal fluid are important for the vaginal health. In addition, vaginal pH varies over a woman’s life span and lactobacilli, with estrogen and glycogen, are the driving forces of this variation. As described by Danielsson et al in their review 1, in young premenarchal girls, the microbiota is mostly similar to the skin and the vaginal pH is alkaline or neutral. There will be gradual changes of this microbiota when the estrogen level starts to increase with ovary function. The vaginal epithelium will thicken and become loaded with glycogen that by endogenous degradation will give a pH close to 5 (acidic). The acidity and high concentration of glycogen in the stratified vaginal epithelium will favor rectal lactobacilli, mostly from the gut microbiota, to colonize the vagina. In reproductive-aged women, a restricted group of species in particular Lactobacillus crispatus, Lactobacillus jensenii, Lactobacilus iners, Lactobacillus gasseri and sometimes Lactobacillus reuteri, are normally present in the vaginal secretions 2.
Influence of the microbiota on vaginal health
The presence of the vaginal flora is very important and associated with vaginal health. For example, L. crispatus is known to produce hydrogen peroxide (H2O2) which, together with some ions and other compounds present in the vaginal epithelium, forms strong toxic oxydants harmful to other invading organisms 1. Lactobacili also produce bacteriocins which are antibacterial molecules able to create membrane permeabilization of potential pathogens, inducing their destruction. Finally, the action of H2O2 and bacteriocins is also potentiated by the presence of the lactic acid produced by fermentation in the niche. Therefore, these examples show the importance of the vaginal flora in the maintenance of the vaginal health and some vaginal pathologies have already been showed to be associated with a disturbance of this flora.
Consequences of a disturbance in the microbiota
Bacterial vaginosis for example affects from 8 to more than 30% of reproductive-age women in industrialized countries. The prevalence increases with age and is even more present in African-American and African women 3 4 5, even if some women with bacterial vaginosis remain asymptomatic. Bacterial vaginosis, first considered as an infection that can be easily treated with antibiotics, has a high recurrence rate. However, acute and chronic infections, can affect the quality of life in women, and secondary complications, such as increased risk for preterm labor and preterm delivery, and postoperative abortive infections 4 6 may arise from persistent infection such as bacterial vaginosis 7. In addition, Studies have shown that absence or depletion of lactobacilli associated with overgrowth of pathogens causing bacterial vaginosis results in significantly increased risk for HIV, gonorrhea, Chlamydia and herpes simplex virus infections. Bacterial vaginosis is therefore an indicator of increased susceptibility to Sexually Transmitted Diseases (STDs) 8. Yet therapeutic approaches to treatment and prevention of urogenital infections have remained almost unchanged for many years with antibiotics as main used therapy despite their well documented side effects. In addition antimicrobial resistances make these therapies less effective.
Pharmabiotics™: a new therapeutic approach
Experimental observations also suggest potential pharmacological benefits for probiotics in bacterial vaginosis. In the case of probiotics with pharmaceutical potential, we refer to pharmabiotics™.
Since the 1980′s, taking into account the importance of lactobacilli in vaginal health and their rarefaction in bacterial vaginosis, several research groups have attempted to identify suitable candidates/strains for vaginal colonization. Administration of lactobacilli orally or directly into the vagina via a capsule is an effective means of boosting content of the flora and overcoming some pathogens or reducing their ability to dominate. This seems to be true for the treatment of bacterial vaginosis since several clinical trials showed a positive effect of some Pharmabiotic™ strains in the treatment or recurrence of bacterial vaginosis 11 12.
In conclusion, in the case of bacterial vaginosis different strains appear as potential pharmabiotics™ but, as it is also the case for the intestinal microflora, effects are strain dependent. This argues for research and development of new Pharmabiotic™ strains having beneficial effect through different mechanisms adapted to woman microflora and to the physiopathology and type of Bacterial vaginosis encountered.
1 Danielsson et al, Ann. N. Y. Acad. Sci, 2011
2 Hillier S.L. et al, Eds 289-307, The McGraw-Hill companies, New York, 2008
3 Moi et al, In J STD&AIDS, 1990
4 Schwebeke et al, Curr Infect Dis Reports, 2009
5 Taha et al, AIDS, 1998
6 Leitich et al, Am J Obstet Gynecol, 2003
7 Flynn et al, J Fam Pract, 1999
8 Reid et al, MedGenMed, 2004
9 Anukam et al, Microbes and Infection, 2006
10 Larsson et al, BMC Women’s health, 2008
11 Ozkinay et al, BJOG: An International Journal of Obstetrics and Gynecology, 1993
12 Falagas et al, Clin Microbiol Infect, 2007