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Scientific outline of potential BV treatments (part 3)
Alternative solutions:
Probiotics have been shown to modulate vaginal microbiota”:
“In the human vagina, certain Lactobacillus strains can act as probiotics, preventing the growth of BV-associated bacteria through two main mechanisms: the inhibition of pathogens adhesion to vaginal epithelium (Machado et al., 2013); and the production of antimicrobial compounds like hydrogen peroxide (Mastromarino et al., 2002), lactic acid (Boskey et al., 2001) and bacteriocins (Aroutcheva et al., 2001b). Diverse pharmaceutical formulations containing probiotic lactobacilli strains have reduced BV symptoms, improved the vaginal microflora profile, being usually well-tolerated (Rossi et al., 2010;Hantoushzadeh et al., 2012; Facchinetti et al., 2013; Vujic et al., 2013; Vicariotto et al., 2014). “
“In contrast, despite their therapeutic potential, some clinical trials have not detected a significant improvement in BV management (Falagas et al., 2007). Alternatively, probiotics have been proposed as adjuvants to antibiotic therapy [[meaning, using probiotics following the use of antibiotics]]. Several combinations of metronidazole, clindamycin or tinidazole with lactobacilli probiotic preparations have displayed promising results in BV treatment since they have been associated with high cure rates, low recurrence or quick re-establishment of an healthy vaginal microflora (Marcone et al., 2010; Bodean et al., 2013; Recine et al., 2016).”
“Probiotics have also been used in an attempt to specifically deal with BV biofilms. Remarkably, in 2007, Saunders and colleagues showed that L. reuteri RC-14 was able to disruptin vitro G. vaginalis biofilms (Saunders et al., 2007). Later, McMillan and colleagues demonstrated that probiotic L. reuteri RC-14 and L. rhamnosus GR-1 were able to incorporate themselves into BV-biofilm, composed by G. vaginalis and A. vaginae, causing both the disruption of the biofilm structure and bacterial cell death (McMillan et al., 2011). These findings provide some evidence of how lactobacilli probiotics might interfere with an abnormal vaginal microflora, reinforcing the hypothesis that probiotics could eradicate vaginal pathogenic biofilms and restore the normal microflora in in vivo situations.”
“It has also been proposed that prebiotics [[such as the product Multigyn FloraPlus]], nutritional substances that stimulate the growth of probiotics, could be used as alternative to treat BV (Roberfroid, 2007). Interestingly, Rousseau and colleagues demonstrated that prebiotic preparations containing oligosaccharides were able to promote the growth of beneficial lactobacilli strains but not of the pathogenic microorganisms often found in urogenital infections including G. vaginalis (Rousseau et al., 2005). “
“Later, Zeng and colleagues compared the efficacy of a prebiotic gel containing sucrose with 0.75% metronidazole vaginal gel to treat BV (Zeng et al., 2010). In that study, the prebiotic gel displayed a similar therapeutic cure rate to metronidazole, having a major advantage of quicker restoration of the normal vaginal microflora. Recently, Coste and colleagues evaluated the efficacy and safety of another prebiotic gel, applied as adjuvant therapy [[combined with antibiotic treatment]], in women treated for BV and showed an improved recovery of the normal vaginal flora, reducing the risk of recurrences (Coste et al., 2012).
Plant-derived compounds:
“Surprisingly, up to now only one study evaluated the capability of plant-derived compound to eradicate BV biofilms. Interestingly, Braga and colleagues showed that thymol, a molecule present in thyme essential oil, had an inhibitory effect upon both newly formed and mature G. vaginalis biofilms, which supports the importance of exploring essential oils and their main constituents as therapeutic alternative to treat BV (Braga et al., 2010). Furthermore, the expectations on essential oils as effective agents against BV-biofilms can be inferred from studies in other related vaginal biofilms (Palmeira-de-Oliveira et al., 2012; Bogavac et al., 2015).” [[The suggested delivery was through douche]].
Acidifying/buffering agents:
-“Recently, Bahamondes and colleagues verified that a soap containing lactic acid and lactoserum could be used for external intimate hygiene, reducing BV recurrence after treatment with oral metronidazole (Bahamondes et al., 2011). “
-“Interestingly, vitamin C, when coated with silicon, allowed the constant release of the active agent, resulting in a long-lasting vaginal low pH and prevention of vaginal irritation (Polatti et al., 2006). Other studies reported an effective and safe use of vaginal vitamin C tablets in BV treatment (Petersen et al., 2011), contributing to improve abnormal vaginal pH and microflora, especially in pregnant women (Zodzika et al., 2013). Additionally, the regular use of vitamin C during 6 days per month, for 6 months after successful BV treatment, was shown to decrease the risk of BV recurrence (Krasnopolsky et al., 2013).
-“Another alternative comes in the form of buffering agents. Polycarbophil [[like the product Replens]] is a weak poly-acid that it is able to adhere to vaginal epithelial cells, acting as a buffer in the vaginal secretions (Milani et al., 2000). “
-“Another agent that has been long used in the treatment of vaginal infections is boric acid (Van Slyke et al., 1981) [[This could be the 600 mg tablets from brands pH-D, BoriCap, Bona Dea, or Boric Balance as of a recent Google search]]. Recently, Reichman and colleagues reported that the use of boric acid in combination with a nitroimidazole reduce the BV recurrence (Reichman et al., 2009), suggesting a potential impact on BV biofilms. However, this need to be further studied and in vitro biofilm experiments will elucidate the role of boric acid in BV prevention.”
Conclusions and future directions:
BV current approved therapies are not sufficient to deal with this multi-species biofilm-related vaginal disorder. Future, research should address biofilm communities with a particular emphasis on multi-species biofilms, a topic that only recently emerged (Castro and Cerca, 2015). By properly addressing the complex interactions established in multi-species biofilms, novel strategies will hopefully overcome the high recurrence and relapse rates associated with BV.
Probiotics have been shown to modulate vaginal microbiota”:
“In the human vagina, certain Lactobacillus strains can act as probiotics, preventing the growth of BV-associated bacteria through two main mechanisms: the inhibition of pathogens adhesion to vaginal epithelium (Machado et al., 2013); and the production of antimicrobial compounds like hydrogen peroxide (Mastromarino et al., 2002), lactic acid (Boskey et al., 2001) and bacteriocins (Aroutcheva et al., 2001b). Diverse pharmaceutical formulations containing probiotic lactobacilli strains have reduced BV symptoms, improved the vaginal microflora profile, being usually well-tolerated (Rossi et al., 2010;Hantoushzadeh et al., 2012; Facchinetti et al., 2013; Vujic et al., 2013; Vicariotto et al., 2014). “
“In contrast, despite their therapeutic potential, some clinical trials have not detected a significant improvement in BV management (Falagas et al., 2007). Alternatively, probiotics have been proposed as adjuvants to antibiotic therapy [[meaning, using probiotics following the use of antibiotics]]. Several combinations of metronidazole, clindamycin or tinidazole with lactobacilli probiotic preparations have displayed promising results in BV treatment since they have been associated with high cure rates, low recurrence or quick re-establishment of an healthy vaginal microflora (Marcone et al., 2010; Bodean et al., 2013; Recine et al., 2016).”
“Probiotics have also been used in an attempt to specifically deal with BV biofilms. Remarkably, in 2007, Saunders and colleagues showed that L. reuteri RC-14 was able to disruptin vitro G. vaginalis biofilms (Saunders et al., 2007). Later, McMillan and colleagues demonstrated that probiotic L. reuteri RC-14 and L. rhamnosus GR-1 were able to incorporate themselves into BV-biofilm, composed by G. vaginalis and A. vaginae, causing both the disruption of the biofilm structure and bacterial cell death (McMillan et al., 2011). These findings provide some evidence of how lactobacilli probiotics might interfere with an abnormal vaginal microflora, reinforcing the hypothesis that probiotics could eradicate vaginal pathogenic biofilms and restore the normal microflora in in vivo situations.”
“It has also been proposed that prebiotics [[such as the product Multigyn FloraPlus]], nutritional substances that stimulate the growth of probiotics, could be used as alternative to treat BV (Roberfroid, 2007). Interestingly, Rousseau and colleagues demonstrated that prebiotic preparations containing oligosaccharides were able to promote the growth of beneficial lactobacilli strains but not of the pathogenic microorganisms often found in urogenital infections including G. vaginalis (Rousseau et al., 2005). “
“Later, Zeng and colleagues compared the efficacy of a prebiotic gel containing sucrose with 0.75% metronidazole vaginal gel to treat BV (Zeng et al., 2010). In that study, the prebiotic gel displayed a similar therapeutic cure rate to metronidazole, having a major advantage of quicker restoration of the normal vaginal microflora. Recently, Coste and colleagues evaluated the efficacy and safety of another prebiotic gel, applied as adjuvant therapy [[combined with antibiotic treatment]], in women treated for BV and showed an improved recovery of the normal vaginal flora, reducing the risk of recurrences (Coste et al., 2012).
Plant-derived compounds:
“Surprisingly, up to now only one study evaluated the capability of plant-derived compound to eradicate BV biofilms. Interestingly, Braga and colleagues showed that thymol, a molecule present in thyme essential oil, had an inhibitory effect upon both newly formed and mature G. vaginalis biofilms, which supports the importance of exploring essential oils and their main constituents as therapeutic alternative to treat BV (Braga et al., 2010). Furthermore, the expectations on essential oils as effective agents against BV-biofilms can be inferred from studies in other related vaginal biofilms (Palmeira-de-Oliveira et al., 2012; Bogavac et al., 2015).” [[The suggested delivery was through douche]].
Acidifying/buffering agents:
-“Recently, Bahamondes and colleagues verified that a soap containing lactic acid and lactoserum could be used for external intimate hygiene, reducing BV recurrence after treatment with oral metronidazole (Bahamondes et al., 2011). “
-“Interestingly, vitamin C, when coated with silicon, allowed the constant release of the active agent, resulting in a long-lasting vaginal low pH and prevention of vaginal irritation (Polatti et al., 2006). Other studies reported an effective and safe use of vaginal vitamin C tablets in BV treatment (Petersen et al., 2011), contributing to improve abnormal vaginal pH and microflora, especially in pregnant women (Zodzika et al., 2013). Additionally, the regular use of vitamin C during 6 days per month, for 6 months after successful BV treatment, was shown to decrease the risk of BV recurrence (Krasnopolsky et al., 2013).
-“Another alternative comes in the form of buffering agents. Polycarbophil [[like the product Replens]] is a weak poly-acid that it is able to adhere to vaginal epithelial cells, acting as a buffer in the vaginal secretions (Milani et al., 2000). “
-“Another agent that has been long used in the treatment of vaginal infections is boric acid (Van Slyke et al., 1981) [[This could be the 600 mg tablets from brands pH-D, BoriCap, Bona Dea, or Boric Balance as of a recent Google search]]. Recently, Reichman and colleagues reported that the use of boric acid in combination with a nitroimidazole reduce the BV recurrence (Reichman et al., 2009), suggesting a potential impact on BV biofilms. However, this need to be further studied and in vitro biofilm experiments will elucidate the role of boric acid in BV prevention.”
Conclusions and future directions:
BV current approved therapies are not sufficient to deal with this multi-species biofilm-related vaginal disorder. Future, research should address biofilm communities with a particular emphasis on multi-species biofilms, a topic that only recently emerged (Castro and Cerca, 2015). By properly addressing the complex interactions established in multi-species biofilms, novel strategies will hopefully overcome the high recurrence and relapse rates associated with BV.
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