Fighting polymicrobial biofilms in bacterial vaginosis

Abstract

Bacterial vaginosis (BV) is the most common cause of vaginal discharge and is often associated with other health consequences mainly in pregnant women. BV is described by an imbalance in the vaginal microbiota where strictly and facultative anaerobic bacteria outgrow the lactic acid- and hydrogen peroxide-producing Lactobacillus species. The species involved in BV are capable to grow and form a polymicrobial biofilm in the vaginal epithelium. The treatment of BV is usually performed using broad-spectrum antibiotics, including metronidazole and clindamycin. However, these conventional treatments are associated with high recurrence rates. The BV polymicrobial biofilm may have an important role on the treatment outcome and is accounted as one of the factors for treatment failure. Other possible reasons for treatment failure include the presence of species resistant to antibiotics or the chance of reinfection after treatment. Therefore, novel strategies to increase the rates of treatment have been studied namely the use of probiotics and prebiotics, acidifying agents, antiseptics, plant-based products, vaginal microbiota transplantation, and phage endolysins. Although some of them are still in an initial phase of development with very preliminary results, they show great perspectives for application. In this review, we aimed to study the role of the polymicrobial nature of BV in treatment failure and explore a few alternatives for treatment.

FIGURE 1

Representation of the vaginal microbiome in health and bacterial vaginosis. The healthy vaginal microbiome is dominated by Lactobacillus species that produce lactic acid and hydrogen peroxide and create an acidic environment. In bacterial vaginosis, the vaginal microbiome is highly colonized by anaerobic species that interact and develop a polymicrobial biofilm on the vaginal epithelium. The most common symptoms of infection are the presence of a vaginal discharge and a strong smell, and an increase of vaginal pH. Figure created with BioRender.com.

FIGURE 2

Polymicrobial biofilm development model in bacterial vaginosis. The first colonizer adheres to the vaginal epithelium, causes the displacement of Lactobacillus species, and starts the formation of biofilm. Following colonizers join the formed biofilm and increase its biomass. When the biofilm is mature, epithelial vaginal cells, covered in bacteria forming biofilm, are detached (clue cells). Figure created with BioRender.com.

FIGURE 3

Schematic representation of bacterial vaginosis cure and recurrence after antibiotic treatment. A case of recurrence may occur either by the reinfection with anaerobic pathogens after the antibiotic treatment or caused by the antimicrobial resistance of bacteria and failure of antibiotics in eliminating the biofilm that recovers its capacity to grow and develop the infection. Figure created with BioRender.com.

FIGURE 4

Alternative treatments for bacterial vaginosis. New strategies to treat this infection include the use of probiotics, prebiotics, acidifying agents, antiseptics, plant‐based products, vaginal microbiome transplantation, and phage endolysins. Figure created with BioRender.com.