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Lactobacillus, in vaginitis [keywords]
- Lactobacillus plantarum P17630 for preventing Candida vaginitis recurrence: a retrospective comparative study. [Journal Article]
- Eur J Obstet Gynecol Reprod Biol 2014 Nov.:136-9.
Recurrence is a frequent complaint of patients with vulvovaginal candidiasis (VVC). Although the pathogenesis of VVC remains a controversial issue, disruption of the balance between the vaginal microbiota may facilitate overgrowth by Candida. Some probiotic bacterial strains can suppress Candida albicans; Lactobacillus plantarum P17630 is able to attach to vaginal epithelial cells and significantly reduce the adhesion of C. albicans.To evaluate the effect of the application of Lactobacillus plantarum P17630 in restoring the vaginal microbiota and prevention of relapses among women with acute VVC undergoing conventional (azole) local and main therapy.Retrospective comparative study. We recruited 89 women with a diagnosis of VVC, who were placed into two groups on the basis of reported treatment. The control group was treated with a daily dose of 2% clotrimazole vaginal cream at bedtime for 3 days, followed by vaginal application of a capsule containing lubricant once a day for 6 days and then once a week for another 4 weeks. The probiotic group was treated with the same azole-based protocol but followed by vaginal application of a capsule containing Lactobacillus plantarum P17630 (>108CFU) once a day for 6 days and then once a week for another 4 weeks beginning the day following clotrimazole discontinuation. Clinical and diagnostic patterns were monitored for three months of follow-up.At the end of study the probiotic-treated women showed a statistically significant increase in Lactobacillus values "+++" (80% versus 40%, p<0.001) and a better subjective resolution of symptoms such as vaginal discomfort described as burning or itching (90% versus 67.5%, p<0.03). Among controls there was a non-significant increase at 3 months of recurrence of infection, but a significant increase of women with value of pH=5 or >5.Although the results of different studies are controversial, most have suggested use of probiotics in the prevention or treatment of VVC, and no adverse effects have been reported. Our data with L. plantarum P17630 (Gyno-Canesflor - Bayer) confirm the role of this specific strain as a potential empirical preventive agent for reducing vaginal discomfort after conventional treatment of acute VVC and shifting the vaginal milieu toward a predominance of lactobacilli with an improvement of the vaginal pH value.
- Effectiveness of the two microorganisms Lactobacillus fermentum LF15 and Lactobacillus plantarum LP01, formulated in slow-release vaginal tablets, in women affected by bacterial vaginosis: a pilot study. [Journal Article]
- J Clin Gastroenterol 2014 Nov-Dec.:S106-12.
Bacterial vaginosis (BV) is the most common reason for abnormal vaginal discharge in reproductive-age women and one of its most important causative agents is the gram-variable bacterium Gardnerella vaginalis. BV is not accompanied by significant local inflammation, whereas the "fishy odor" test is always positive. In contrast, aerobic vaginitis (AV) is predominantly associated with Escherichia coli, but Streptococcus agalactiae and Staphylococcus aureus are also involved. Standard treatment of BV consists of oral or intravaginal antibiotics, although these are unable to spontaneously restore normal flora characterized by a high concentration of lactobacilli. The main limitation is the inability to offer a long-term defensive barrier, thus facilitating relapses and recurrences. This study was undertaken firstly to assess the ability of selected lactobacilli to in vitro antagonize G. vaginalis to determine an association with a strain able to inhibit E. coli, thus identifying a possible use in AV. The second step of the study was to conduct a human pilot trial in women affected by BV using an association of the most promising and active bacteria.For this purpose, neutralized supernatants of individual lactobacilli were tested at percentages ranging from 0.5% to 4% to determine their ability to hinder the growth of G. vaginalis American Type Culture Collection 10231. The bacterium that was able to exert the strongest inhibition was subsequently tested with Lactobacillus plantarum LP01 in a human intervention, placebo-controlled, pilot trial involving 34 female subjects (aged between 18 and 50, mean 34.7±8.9, no menopausal women) diagnosed with BV. The 2 microorganisms Lactobacillus fermentum LF15 (DSM 26955) and L. plantarum LP01 (LMG P-21021) were delivered to the vagina by means of slow-release vaginal tablets, also containing 50 mg of tara gum. The amount of each strain was 400 million live cells per dose. The women were instructed to apply a vaginal tablet once a day for 7 consecutive nights, followed by 1 tablet every 3 nights for a further 3-week application (acute phase) and, finally, 1 tablet per week to maintain a long-term vaginal colonization against possible recurrences. A clinical examination was performed and the Nugent score was quantified for each patient at enrollment (d0), after 28 days (d28), and at the end of the second month of relapse prevention (d56). A statistical comparison was made between d28, or d56, and d0, and between d56 and d28 to quantify the efficacy against possible recurrences.L. fermentum LF15 showed the strongest in vitro inhibitory activity towards G. vaginalis American Type Culture Collection (ATCC) 10231 after both 24 and 48 hours. In the human trial, the 2 lactobacilli selected, namely L. fermentum LF15 and L. plantarum LP01, significantly reduced the Nugent score below the threshold of 7 after 28 days in 22 patients of 24 in the active group (91.7%, P<0.001). Eight women (33.3%) recorded a Nugent score between 4 and 6, evidence of an intermediate situation, whereas the remaining 14 (58.3%) showed a score <4, therefore suggesting the restoration of physiological vaginal microbiota. At the end of the second month, only 4 women registered a Nugent score >7, definable as BV (16.7%, P=0.065 compared with d28). In the placebo group, no significant differences were recorded at any time.BV, also known as vaginal bacteriosis is the most common cause of vaginal infection in women of childbearing age. Furthermore, BV is often asymptomatic as about 50% of women with this condition have no symptoms at all and the prevalence rate in apparently healthy women is around 10%. This study suggests the ability of the 2 strains L. fermentum LF15 and L. plantarum LP01 to counteract acute Gardnerella infections effectively and significantly improve the related uncomfortable symptoms in a very high percentage of women. This could be partially attributed to the presence of tara gum, which is able to create a mechanical barrier against Gardnerella on the surface of vaginal mucosa as a primary mechanism. Furthermore, long-term physiological protection seems to be established, thanks to the integration of the 2 lactobacilli into the vaginal microbiota and to their adhesion to the epithelial cells of the mucosa. In the light of the additional in vitro inhibitory activity against E. coli, their prospective use in AV could also prove interesting.
- Characterization of culturable vaginal Lactobacillus species among women with and without bacterial vaginosis from the United States and India: a cross-sectional study. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- J Med Microbiol 2014 Jul; 63(Pt 7):931-5.
Lactobacillus species play an integral part in the health of the vaginal microbiota. We compared vaginal Lactobacillus species in women from India and the USA with and without bacterial vaginosis (BV). Between July 2009 and November 2010, a cross-sectional study was conducted among 40 women attending a women's health clinic in Mysore, India, and a sexually transmitted diseases clinic in San Francisco, USA. Women were diagnosed with BV using Amsel's criteria and the Nugent score. Lactobacillus 16S rDNA was sequenced to speciate the cultured isolates. Ten Indian and 10 US women without BV were compared with an equal number of women with BV. Lactobacilli were isolated from all healthy women, but from only 10% of Indian and 50% of US women with BV. 16S rDNA from 164 Lactobacillus colonies was sequenced from healthy women (126 colonies) and women with BV (38 colonies). Seven cultivable Lactobacillus species were isolated from 11 Indian women and nine species from 15 US women. The majority of Lactobacillus species among Indian women were L. crispatus (25.0%), L. jensenii (25.0%) and L. reuteri (16.7%). Among US women, L. crispatus (32.0%), L. jensenii (20.0%) and L. coleohominis (12.0%) predominated. L. jensenii and L. crispatus dominated the vaginal flora of healthy Indian and US women. Indian women appeared to have a higher percentage of obligate heterofermentative species, suggesting the need for a larger degree of metabolic flexibility and a more challenging vaginal environment.
- Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor(®)) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. [Journal Article, Research Support, Non-U.S. Gov't]
- Breast Cancer Res Treat 2014 Jun; 145(2):371-9.
Phase I pharmacokinetic (PK) study assessed circulating estrogens in breast cancer (BC) patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor(®)). 16 women on NSAI with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor(®) for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks. Primary outcomes were serum concentrations and PK of E3, estradiol (E2), and estrone (E1) using highly sensitive gas chromatography-mass spectrometry. Secondary outcomes were clinical measures for efficacy and side effects; microscopic changes in vaginal epithelium and microflora; and changes in serum FSH, LH, and sex hormone-binding globulin. Compared with baseline, serum E1 and E2 did not increase in any of the women at any time following vaginal application. Serum E3 transiently increased after the first application in 15 of 16 women, with a maximum of 168 pg/ml 2-3 h post-insertion. After 4 weeks, serum E3 was slightly increased in 8 women with a maximum of 44 pg/ml. The vaginal atrophy resolved or improved in all women. The product was well tolerated, and discontinuation of therapy was not observed. The low-dose 0.03 mg E3 and Lactobacillus acidophilus vaginal tablets application in postmenopausal BC patients during AI treatment suffering from vaginal atrophy lead to small and transient increases in serum E3, but not E1 or E2, and therefore can be considered as safe and efficacious for treatment of atrophic vaginitis in BC patients taking NSAIs.
- Curative effect of the probiotic strain Lactobacillus fermentum L23 in a murine model of vaginal infection by Gardnerella vaginalis. [Journal Article, Research Support, Non-U.S. Gov't]
- Lett Appl Microbiol 2014 Jul; 59(1):93-8.
Bacterial vaginosis is a common vaginal infection characterized by changes in the vaginal microbiota. The objective of this work was to evaluate the colonization ability and curative effect of Lactobacillus fermentum L23 after vaginal administration in female BALB/c mice infected with Gardnerella vaginalis. One dose of Lact. fermentum L23 containing 10(9 ) CFU ml(-1) was administered locally in a murine vaginal model. L23 colonized the vaginal tract of BALB-c mice after one inoculation. The infection by G. vaginalis in a murine model was induced by vaginal administration of a 1 × 10(6 ) CFU ml(-1) suspension. Infection with the pathogen was observed in the vaginal tract for 4 days. At 144 h after inoculation, levels of 4 log10 CFU ml(-1) were observed. The curative effect of L23 was evaluated with one administration at 1 × 10(9 ) CFU ml(-1) 72 h after the inoculation with G. vaginalis. Lactobacillus fermentum L23 inhibited the growth of G. vaginalis. The results of suppression of G. vaginalis using different concentrations of L23 were favourable due that these concentrations are normally used in commercial formulas. The obtained results indicate that Lact. fermentum L23 inhibited the growth of G. vaginalis. Therefore, L23 might be used as a potential biotherapeutic agent for the elimination of this bacterium.The use of the probiotic strain Lactobacillus fermentum L23 as a biotherapeutic agent can be expected to prevent and treat genital infections, particularly recurrent bacterial vaginosis, with similar concentrations to those normally used in commercial formulas. It is likely that the use of this probiotic strain for the treatment of bacterial vaginosis will provide a natural and nontoxic treatment modality.
- Probiotics in the prevention of recurrences of bacterial vaginosis. [Journal Article, Review]
- Altern Ther Health Med 2014.:52-7.
Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women during their fertile years. BV prevalence runs from 10%-50%, in part due to the high rate of recurrence after standard treatment. Women with BV may experience a decreased quality of life and are at risk of serious obstetric complications. Limited data are available regarding optimal management strategies for preventing recurrence of BV, emphasizing the importance of the availability of a comprehensive source of scientific information and therapeutic strategies.The aim of this study was to evaluate the frequency and clinical relevance of the recurrence of BV and to collect and review data about prophylactic approaches based on probiotic supplementation with lactobacilli (LB).A review of the literature was performed, based on combinations of the following keywords: bacterial vaginosis, bacterial vaginosis recurrences, vaginal discharge, vaginal flora, LB, Lactobacillus rhamnosus, and probiotic supplementation.The studies were evaluated in terms of the cure rates for BV, incidence of recurrence of BV, decrease in patients' discomfort, maintenance of a healthy vaginal recolonization, and occurrence of complications and side effects.Recurrence of BV after standard therapy is a relevant clinical problem, with an incidence of 30%-40% and a significant impact on women's quality of life and on their risk of infrequent but serious obstetric complications. Therefore, finding effective prophylactic therapies to avoid or decrease the recurrence of BV is important. Even when they are effective, typical antibacterial regimens for long-term maintenance are known to have side effects. Different schemes of treatment with exogenous LB have proven effective in preventing recurrence of BV, even in patients at high risk for relapse.Probiotic supplementation with vaginal LB proved to be crucial in hindering bacteria growth after antibiotic therapy; therefore this intervention may be considered a new adjuvant treatment for preventing recurrence of BV, even in high-risk patients.
- Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. [Journal Article, Research Support, Non-U.S. Gov't]
- J Infect Dis 2014 Jun 15; 209(12):1989-99.
Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health.To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia).Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8.We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis.
- Potential influence of the microbiome on infertility and assisted reproductive technology. [Journal Article, Research Support, N.I.H., Intramural, Review]
- Semin Reprod Med 2014 Jan; 32(1):35-42.
Although an altered vaginal microbiota has been demonstrated to affect parturition, its role in assisted reproductive technologies is uncertain. Nevertheless, the effect of known pathogens such as Mycoplasma tuberculosis, Chlamydia trachomatis, and Neisseria gonorrhoeae is clear, causing subclinical changes thought to be risk factors in subfertility. The Human Microbiome Project (HMP) has allowed for metagenomic studies to aid in characterizing normal vaginal flora. Recent findings from the HMP demonstrate that many different species of Lactobacillus are present in the vaginal tract, with a few that predominate. Studies that characterize the vaginal microbiome in assisted reproductive technology support the hypothesis that colonizing the transfer-catheter tip with Lactobacillus crispatus at the time of embryo transfer may increase the rates of implantation and live birth rate while decreasing the rate of infection. In addition, there is some evidence that a progesterone-resistant endometrium might increase the risk of an abnormal vaginal microbiome.
- Modulating the vaginal microbiome: the need for a bridge between science and practice. [Journal Article, Review]
- Semin Reprod Med 2014 Jan; 32(1):28-34.
Infections of the urinary and reproductive tracts continue to afflict hundreds of millions of women and girls each year. For those fortunate enough to have access to medical care, the diagnostic and treatment measures used on them have changed little in 40 years and remain far from adequate. The development of alternatives, such as probiotics, has been hindered by lack of funding, but now face bureaucratic barriers that reflect an outdated regulatory system more concerned with policies than care for the patient. The technological advances emerging from human microbiome studies are making it possible to generate a completely new understanding of how microbes interact with the host, what influences them, and when the result is an aberration requiring intervention. But until bridges are built between scientific progress and practice, it is women and girls who will continue to receive suboptimal care for their often persistent and debilitating conditions.
- Benzoyl peroxide formulated polycarbophil/carbopol 934P hydrogel with selective antimicrobial activity, potentially beneficial for treatment and prevention of bacterial vaginosis. [Journal Article]
- Infect Dis Obstet Gynecol 2013.:909354.
The human vagina is colonized by a variety of indigenous microflora; in healthy individuals the predominant bacterial genus is Lactobacillus while those with bacterial vaginosis (BV) carry a variety of anaerobic representatives of the phylum Actinobacteria. In this study, we evaluated the antimicrobial activity of benzoyl peroxide (BPO) encapsulated in a hydrogel against Gardnerella vaginalis, one of the causative agents of BV, as well as indicating its safety for healthy human lactobacilli. Herein, it is shown that in well diffusion assays G. vaginalis is inhibited at 0.01% hydrogel-encapsulated BPO and that the tested Lactobacillus spp. can tolerate concentrations of BPO up to 2.5%. In direct contact assays (cells grown in a liquid culture containing hydrogel with 1% BPO or BPO particles), we demonstrated that hydrogels loaded with 1% BPO caused 6-log reduction of G. vaginalis. Conversely, three of the tested Lactobacillus spp. were not inhibited while L. acidophilus growth was slightly delayed. The rheological properties of the hydrogel formulation were probed using oscillation frequency sweep, oscillation shear stress sweep, and shear rate sweep. This shows the gel to be suitable for vaginal application and that the encapsulation of BPO did not alter rheological properties.