Abstract
Oral administration of a probiotic mixture (PM; Respecta®) consisting of Lactobacillus rhamnosus HN001 (L1), Lactobacillus acidophilus La-14 (L2), and lactoferrin RCXTM results in colonization of these probiotics in the vagina of healthy women. Therefore, we examined whether vaginal colonization of the PM ingredients L1 and L2 could attenuate bacterial vaginosis (BV). BV was induced in mice via β-estradiol-3-benzoate-induced immunosuppression and intravaginal inoculation with Gardnerella vaginalis (GV). Inflammatory markers were analyzed using enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, and flow cytometry. Oral or intravaginal administration of PM resulted in colonization of L1 and L2 in the vagina. Oral or intravaginal administration of L1, L2, or PM significantly inhibited GV-induced epithelial cell disruption, myeloperoxidase activity, NF-κB activation, and IL-1β and TNF-α expression (p < 0.05). Administration of these probiotics also inhibited IL-17 and RORγt expression but increased IL-10 and Foxp3 expression. Of these probiotics, L2 most effectively attenuated GV-induced BV, followed by L1 and PM. Oral administration was more effective against GV-induced BV than intravaginal administration. L1 and L2 also significantly inhibited the adherence of GV to HeLa cells (a human cervical cancer cell line) and GV growth in vitro. In addition, L1 and L2 inhibited lipopolysaccharide-induced NF-κB activation in macrophages and the differentiation of splenocytes into Th17 cells in vitro, but increased their differentiation into Treg cells. Our study suggests that L1, L2, and PM attenuated GV-induced vaginosis by regulating both vaginal and systemic innate and adaptive immune responses rather than direct competition or killing of GV in the vagina.
Highlights
The vaginal microbiota, which is dominated by lactobacilli, plays an important role in maintaining female health [1,2]
Oral administration of the probiotic mixture (PM; containing Lactobacillus rhamnosus HN001 (L1) and L2) resulted in the colonization of L1 and L2 in the vaginas of healthy women [18]. To determine whether these probiotics could colonize the vaginas of mice, we orally or intravaginally administered PM or one of its probiotic components, L1 or L2, and assessed the vaginas from the presence of attached probiotics by Quantitative Polymerase Chain Reaction (qPCR) (Figure 1)
L1 and L2 were detected in the vaginas of mice that were orally or intravaginally administered PM, and more L2 was detected than L1
Summary
The vaginal microbiota, which is dominated by lactobacilli, plays an important role in maintaining female health [1,2]. Disturbance of the vaginal microbiota allows infection by various pathogens such as Gardnerella vaginalis (GV) and Atopobium vaginae (AV), resulting in bacterial vaginosis (BV) [3,4]. BV is a common vaginal inflammatory disease in women that is manifested by malodorous discharge and elevated pH [5,6]. Antimicrobial drugs, such as clindamycin and metronidazole, Nutrients 2017, 9, 531; doi:10.3390/nu9060531 www.mdpi.com/journal/nutrients. Lactobacilli are safe probiotics that antagonize pathogens, have anti-inflammatory (anticolitic and antivaginitic) effects [11,12,13,14], and modulate host immunity. It has been shown that oral or vaginal administration of Lactobacillus johnsonii HY7042 attenuated GV-infected BV in mice by inhibiting
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