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Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence
Abstract
Background:
Bacterial vaginosis (BV) is a recurrent disease in women despite treatment by antibiotics. This study investigated the impact of a vaginal probiotic, Lactobacillus crispatus IP174178* (Lc), on the rate of recurrence and time to recurrence.
Methods:
A prospective, multi-centre, double blind, randomised phase III trial in women with at least two documented episodes of BV in the previous year (diagnosis confirmed by presence of three Amsel criteria and a Nugent score ≥7), and who had been clinically cured (i.e., no Amsel criteria) after oral metronidazole treatment (1g/day × 7 days). The patients were randomised to receive vaginal capsules of either Lc or placebo, once a day, for 14 days over the first two menstrual cycles and another 14 days of the same treatment for the following two menstrual cycles. The primary efficacy endpoint was the number of patients with at least one bacteriologically confirmed recurrence of BV.
Results:
Out of 98 assessable patients (mean age 35.7 years), 78 women were evaluated (20 patients had missing data). During the treatment period, 16/39 patients (41%) had at least one recurrence in the placebo group versus 8/39 patients (20.5%) in the Lc group (p=0.0497). The time to recurrence was longer by 28% in the Lc group (3.75 months ± 0.16) vs. the placebo group (2.93 months ± 0.18) (p=0.0298). Tolerability and safety were good in both groups.
Conclusion:
In women with recurrent BV after antibiotics, treatment with Lc IP 174178 administered over four menstrual cycles, could significantly reduce the rate of recurrence and increase the time to recurrence.
... Of the 13 studies with BV and/or molecular VMB composition as outcome, five were judged to have medium, and eight high, overall risk of bias ( Figure 2). Most studies (11/13) were randomised controlled trials, including six with placebo controls, 18,[20][21][22]26,28 two with 'no intervention' controls, 10,19 four with metronidazole or clindamycin controls, 10,21,23,25 and one with a vaginal pH lowering tablet control 24 (two trials included both placebo/'no intervention' and antibiotic controls 10,21 ) ( Table 1). Five clinical trials were judged medium risk 10,18-21 and the other six high risk. ...
... Five clinical trials were judged medium risk 10,18-21 and the other six high risk. [22][23][24][25][26][27][28][29] The two remaining studies (both judged high risk) were pre-post intervention studies in women receiving a vaginal probiotic without an antibiotic. 27,29 Nine of the 14 main results reported in the 13 studies were on BV cure or post-treatment Nugent score improvement (2/9 after initial antibiotic treatment and 7/9 without antibiotic use), nine on BV recurrence (6/9 and 3/9, respectively), and four on BV cure and recurrence (Table 1). ...
... recurrence results in eight randomised controlled trials, six were significant reductions, 10,18,20,23,25,28 two non-significant reductions, 10,21 and one no reduction. 22 The one study that showed no reduction in BV recurrence included women who used the vaginal probiotic during menses only. ...
Background:
Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but did, until recently, not have to be approved as drugs for human use.
Objectives:
We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains.
Search strategy:
We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019.
Selection criteria:
There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison-Hay Gram stain scoring, VVC by culture, wet mount, or PCR, and VMB composition/detection by molecular techniques.
Data collection and analysis:
The authors independently extracted data.
Main results:
All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal.
Conclusions:
Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence-based product development, and to conduct future trials more rigorously. This article is protected by copyright. All rights reserved.
... Researchers are still debating whether BV should be considered as a sexually transmitted infection, given that the chance of getting BV increases with sexual activity (multiple sex partners), vaginal douching, smoking, presence of the IUD, and antibiotic usage [72,73]. In general, the global economic burden of treating symptomatic BV is estimated to be US $4.8 billion annually, yet the prevalence of BV varies in different regions [74,75]. An earlier systematic review by Kenyon et al. in 2013 gathered information on the prevalence of BV from a total of 86 surveys conducted from different parts of the world [76]. ...
... Using L. crispatus IP 174178 as a probiotic, a study in Paris administered the strain intravaginally for 14 days for four menstrual cycles to women with a history of recurrent BV in the past year after seven days of standard treatment oral metronidazole. There was an increase in recurrence time by 28%, and there were a lower number of recurrent cases in the intervention group (20.6%) compared to the placebo group (41%) [74]. There were another two studies that reported the use of a different strain of L. crispatus in BV. ...
Bacterial vaginosis (BV) has been reported in one-third of women worldwide at different life stages, due to the complex balance in the ecology of the vaginal microbiota. It is a common cause of abnormal vaginal discharge and is associated with other health issues. Since the first description of anaerobic microbes associated with BV like Gardnerella vaginalis in the 1950s, researchers have stepped up the game by incorporating advanced molecular tools to monitor and evaluate the extent of dysbiosis within the vaginal microbiome, particularly on how specific microbial population changes compared to a healthy state. Moreover, treatment failure and BV recurrence rate remain high despite the standard antibiotic treatment. Consequently, researchers have been probing into alternative or adjunct treatments, including probiotics or even vaginal microbiota transplants, to ensure successful treatment outcomes and reduce the colonization by pathogenic microbes of the female reproductive tract. The current review summarizes the latest findings in probiotics use for BV and explores the potential of vaginal microbiota transplants in restoring vaginal health.
... Almost all of the clinical trials for BV treatment used Lactobacillus species from the gastrointestinal tract, probably due to how recently sequencing studies revealed that the Lactobacillus species dominating the vaginal microbiome are different from gut Lactobacillus (Tables 1-4). One L. crispatus clinical trial showed promising results for BV, with an 80% remission rate compared with a 59% remission rate in the placebo group 51 . This result is comparable to VMT treatment (80% vs. 80% cure rate based on clinical diagnosis), which suggests that one strain of L. crispatus may be as effective as VMT. ...
... Furthermore, two well-designed, double-blinded clinical trials with L. crispatus CTV-05 (LACTIN-V), administered to the vaginal tract directly after metronidazole treatment, showed a significantly decreased recurrence of bacterial vaginosis and increased L. crispatus colonization 52,53 . In the limited clinical studies described above, L. crispatus treatment resulted in a cure rate of 100% when considered short term and cure rates of 70% and 79.5% based on clinical Amsel's criteria when considering long-term effects 51,53,54 . ...
Bacterial vaginosis (BV) is a condition in which the vaginal microbiome presents an overgrowth of obligate and facultative anaerobes, which disturbs the vaginal microbiome balance. BV is a common and recurring vaginal infection among women of reproductive age and is associated with adverse health outcomes and a decreased quality of life. The current recommended first-line treatment for BV is antibiotics, despite the high recurrence rate. Live biopharmaceutical products/probiotics and vaginal microbiome transplantation (VMT) have also been tested in clinical trials for BV. In this review, we discuss the advantages and challenges of current BV treatments and interventions. Furthermore, we provide our understanding of why current clinical trials with probiotics have had mixed results, which is mainly due to not administering the correct bacteria to the correct body site. Here, we propose a great opportunity for large clinical trials with probiotic strains isolated from the vaginal tract (e.g., Lactobacillus crispatus ) and administered directly into the vagina after pretreatment.
... In women with recurrent BV after antibiotics, Physioflor ® could reduce the rate of recurrence and increase the time to recurrence (Bohbot et al., 2018) To improve vaginal colonization by LACTIN-V, Osel Inc. increased the product dose and designed a novel applicator to facilitate delivery of the powder formulation directly into the vagina. A phase 1 dose-ranging safety trial (ClinicalTrials.gov ...
... Despite the limitations of the study, Physioflor ® slightly reduced the recurrence rate and increased the time to recurrence. The authors emphasized that the use of Physioflor may be a factor that assists in the prevention of BV, and that in order to sustain a long-term benefit, the known risk factors of BV should be considered (Bohbot et al., 2018). ...
In medicine, the 20th century was marked by one of the most important revolutions in infectious-disease management, the discovery and increasing use of antibiotics. However, their indiscriminate use has led to the emergence of multidrug-resistant (MDR) bacteria. Drug resistance and other factors, such as the production of bacterial biofilms, have resulted in high recurrence rates of bacterial diseases. Bacterial vaginosis (BV) syndrome is the most prevalent vaginal condition in women of reproductive age, leading to considerable discomfort. BV can be a consequence of gynecological and obstetric complications, as well as sexually transmitted diseases. Given the decrease in efficiency of antibiotic therapy and high rates of recurrence, probiotics have become promising alternatives for both prevention and treatment of BV, or as an adjuvant to conventional therapy. Currently, Lactobacillus species are the most extensively studied for use as probiotics. Probiotics act through stimulation of the host immune system, competitive exclusion and antimicrobial activity; the latter involves production of substances such as lactic acid, hydrogen peroxide and bacteriocins. Lactobacillus crispatus is considered to be a biomarker of a healthy vaginal tract and is indicated for a probiotic approach to maintaining and restoring of a healthy vaginal ecosystem. Some L. crispatus probiotic strains are already commercially available with encouraging results; however, control of BV syndrome still presents many challenges.
... On the contrary, Lact. crispatus, a biomarker of a healthy vaginal microbiome, has rarely been explored as a potential probiotic candidate [12]. Besides this, considering the dominance of other lactobacilli in the vagina of healthy women, there is a lot of scopes to search and evaluate strains for beneficial characteristics to improve vaginal health. ...
... Commercial probiotic products available for vaginal health are limited and only a few of these are host-specific and have the direct vaginal application [31]. It has been suggested that host-specific microorganisms colonize the host with higher capacity, survive, and exerts specific physiological effect [12]. Thus, there is an urgent need to develop host-specific probiotics for the wellness of the vaginal tract. ...
In this study, Lactobacillus crispatus UBLCp01, Lactobacillus gasseri UBLG36, and Lactobacillus johnsonii UBLJ01 isolated from the vagina of healthy reproductive age Indian women were screened for beneficial probiotic properties. These strains showed the ability to survive acidic and simulated vaginal fluid conditions and could adhere to mucin. Lact. gasseri UBLG36, and Lact. johnsonii UBLJ01 produced d- and l-lactic acid, whereas Lact. crispatus UBLCp01 produced hydrogen peroxide and d- and l-lactic acid. All strains inhibited the growth of pathogens (Escherichia coli, Gardnerella vaginalis, Proteus mirabilis, and Candida albicans) and were capable of co-aggregating with them with varying degrees. Strains secreted exopolysaccharides and formed biofilms under in vitro conditions. Safety assessment showed that these strains had a usual antibiotic susceptibility profile, did not produce hemolysins, gelatinases, and mucin degrading enzymes. Based on strain characteristics and beneficial properties, we believe that these strains are promising candidates for human trials to confirm their ability to prevent/treat vaginal dysbiosis and maintain a healthy vaginal eco-system.
... Lactobacilli-containing vaginal probiotic clinical trials to date have shown mixed results, but eight of the 12 trials showed sufficiently promising efficacy for BV prevention to warrant further investigation 13-24 . Some trials used commercially available probiotic strains (mostly derived from the gut or fermented foods) and others vaginal strains isolated from healthy women 25 , but efficacy signals were similar for the two probiotic strain categories [13][14][15][16][17][18][19][20][21][22][23][24] . None of the trials reported major safety concerns or colonization beyond the dosing period. ...
... With the development of better genomic and culturing methods, we are now on the cusp of a new era in vaginal probiotic research. Past vaginal probiotic studies have shown mixed results [13][14][15][16][17][18][19][20][21][22][23][24] , but almost all of these studies used imprecise VMB assessments based on clinical symptoms and microscopy. The addition of sequencing methods showed that many more women than previously thought are not lactobacilli-dominated after standard antibiotic BV treatment, that host responses to antibiotic and probiotic treatment are highly variable, and that it is possible to differentiate between probiotic strains and 'natural' lactobacilli. ...
Bacterial vaginosis (BV) is associated with HIV acquisition and adverse pregnancy outcomes. Recurrence after metronidazole treatment is high. HIV-negative, non-pregnant Rwandan BV patients were randomized to four groups (n = 17/group) after seven-day oral metronidazole treatment: behavioral counseling only (control), or counseling plus intermittent use of oral metronidazole, Ecologic Femi+ vaginal capsule (containing multiple Lactobacillus and one Bifidobacterium species), or Gynophilus LP vaginal tablet (L. rhamnosus 35) for two months. Vaginal microbiota assessments at all visits included Gram stain Nugent scoring and 16S rRNA gene qPCR and HiSeq sequencing. All interventions were safe. BV (Nugent 7–10) incidence was 10.18 per person-year at risk in the control group, and lower in the metronidazole (1.41/person-year; p = 0.004), Ecologic Femi+ (3.58/person-year; p = 0.043), and Gynophilus LP groups (5.36/person-year; p = 0.220). In mixed effects models adjusted for hormonal contraception/pregnancy, sexual risk-taking, and age, metronidazole and Ecologic Femi+ users, each compared to controls, had higher Lactobacillus and lower BV-anaerobes estimated concentrations and/or relative abundances, and were less likely to have a dysbiotic vaginal microbiota type by sequencing. Inter-individual variability was high and effects disappeared soon after intervention cessation. Lactobacilli-based vaginal probiotics warrant further evaluation because, in contrast to antibiotics, they are not expected to negatively affect gut microbiota or cause antimicrobial resistance.
... En revanche, dans la pré vention des ré cidives de VB, la supplé mentation par probiotiques vaginaux aprè s antibiothé rapie classique de la VB a montré une ré duction du nombre de ré cidives et un allongement du dé lai de survenue de la 1 re ré cidive [140,141]. Une revue systé matique [142] de la litté rature confirme l'effet pré ventif des probiotiques vaginaux vis à vis des ré cidives VB mais pas vis-à -vis des ré cidives de candidoses vaginales. Si plusieurs espè ces de lactobacilles ont dé montré leur efficacité (en particulier L. crispatus et L. gasseri), une é tude ré cente [143] a montré in vitro des activité s bacté riennes diffé rentes selon les souches de L. crispatus et L. gasseri considé ré es. ...
La physiopathologie de la vaginose bactérienne (VB), stade ultime de la dysbiose vaginale, a bénéficié des avancées récentes de la biologie moléculaire, mettant en lumière, entre autres, le rôle important d’Atopobium vaginae. Certaines spécificités immunologiques (variants du TLR4, élévation de l’IL-1β par exemple) permettent d’expliquer les variations de prévalence de cette infection, la faible réponse inflammatoire clinique et cellulaire ainsi que l’action favorisante de la VB sur l’acquisition et l’histoire naturelle de certaines infections sexuellement transmissibles. Ces progrès n’expliquent pas totalement le taux élevé de récidives. Si les facteurs comportementaux comme la consommation de tabac, le stress ou les erreurs hygiéniques sont des causes reconnues de récidive, d’autres pistes commencent à être explorées comme le rôle de la transmission sexuelle, la résistance de certaines bactéries aux imidazolés ou l’absence d’efficacité des traitements classiques sur la dysbiose elle-même. La prise en compte de cette dysbiose vaginale apparaît comme importante voire indispensable pour mieux contrôler l’histoire naturelle de l’infection par les HPV-hr ou améliorer le taux de réussite des FIV. Malgré des résultats hétérogènes, l’utilisation de probiotiques en complément des traitements classiques (antibiotiques imidazolés, chlorure de dequalinium) a démontré un effet préventif sur les récidives de VB. Des études ultérieures sont nécessaires pour personnaliser l’apport de probiotiques (ou de synbiotiques) en fonction des spécificités individuelles du microbiote vaginal.
... Vaginal Tablet Patients with BV received either one Lactobacilluscontaining tablet or placebo daily for 7 days L. brevis (CD2), L. salivarius (FV2) and L. plantarum (FV9) Two weeks after completion of therapy, treatment was successful in 61% of Lactobacillus-treated patients as compared with 19% of those in the placebo group (p < 0.05) (Mastromarino et al., 2008 (Bohbot et al., 2017). ...
Bacterial vaginosis (BV) affects many women and has a high influence on their self-esteem, being associated with huge discomfort and changes in the routines, especially the sexual life. International guidelines recommend the administration of metronidazole, clindamycin or tinidazole orally or intravaginally as the standard treatment. However, the treatment with these antibiotics is associated with high levels of failure and recurrence rates. This may be associated with antibiotic resistance, the inability to eradicate the polymicrobial biofilms, failure to reestablish acidic pH and the lactobacillus-dominated commensal flora. Therefore, it is emergent to study alternative strategies to replace or to be combined with standard therapies in order to prevent and treat BV more efficiently. Alternative strategies may include antimicrobial substances (other antimicrobials, antiseptics and natural compounds) or substances that aim to reestablish the physiologic vaginal environment (probiotics, prebiotics and acidifying agents) while improving the local immunity response. Besides, the development of formulation strategies and new dosage forms and drug delivery systems can improve treatment efficacy and overcome some limitations associated with conventional products.
... The findings showed a reduction of pain symptoms [32]. However, the use of Lactobacillus crispatus was studied as an intravaginal approach by several authors [33][34][35]. ...
Aim of the study:
To evaluate the efficacy of a nutraceutical compound containing Uticlin® (D-mannose, cranberry, bearberry, Olea europaea), inulin, Orthosiphon and Lactobacillus acidophilus, in preventing recurrent urinary tract infections (UTIs) in menopausal women.
Material and methods:
This was a prospective cohort study of menopausal women recruited with a history of recurrent UTIs in the previous twelve months and who intended to treat their bladder problem without the use of antibiotics and/or anti-inflammatories. Women were proposed the use of an oral nutraceutical compound. The drug was taken for ten days, every month. Women were assigned to two parallel cohorts: patients using (group 1) or not using (group 2) this nutraceutical compound. The primary objective of the study was to evaluate the number of women with less than two infective episodes in the 6-month follow-up and less than three episodes in the 12-month follow-up. The secondary endpoints were to evaluate the reduction of related symptoms at 12-month follow-up, according to the Visual Analog Scale (VAS).
Results:
At 6 months of therapy, the reduction in the number of patients with ≥ 2 UTIs was statistically significant (p < 0.05) compared to baseline only in group 1. At 12 months, the number of patients who were disease-free was significantly higher (p < 0.05) in group 1 compared to group 2. Moreover, the improvement of related symptoms was statistically significant (p < 0.05) in group 1, as shown by the reduction in the VAS scale value.
Conclusions:
In menopausal women, the combination of D-mannose, inulin, cranberry, bearberry, Olea europaea, Orthosiphon and Lactobacillus acidophilus SGL 11 per os represents a useful therapy for recurrent UTIs in women wanting a natural approach.
... Intravaginal administration of probiotics was also invented to restore the disrupted vaginal microbiota. Bohbot et al. [168] reported that 28 days intravaginal administration of lyophilised L. crispatus IP 174178 was able to reduce the recurrence rate (20.5%) and prolonged the time for BV recurrence (28%) as compared to placebo-control group. Moreover, vaginal tablet consists of L. fermentum LF15 and L. plantarum LP01 restored the acidity of vaginal pH and the threshold level of Nugent score to below 7 (balanced vaginal microbiota) through the inhibition of G. vaginalis [169]. ...
Human vagina is colonised by a diverse array of microorganisms that make up the normal microbiota and mycobiota. Lactobacillus is the most frequently isolated microorganism from the healthy human vagina, this includes Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii. These vaginal lactobacilli have been touted to prevent invasion of pathogens by keeping their population in check. However, the disruption of vaginal ecosystem contributes to the overgrowth of pathogens which causes complicated vaginal infections such as bacterial vaginosis (BV), sexually transmitted infections (STIs), and vulvovaginal candidiasis (VVC). Predisposing factors such as menses, pregnancy, sexual practice, uncontrolled usage of antibiotics, and vaginal douching can alter the microbial community. Therefore, the composition of vaginal microbiota serves an important role in determining vagina health. Owing to their Generally Recognised as Safe (GRAS) status, lactobacilli have been widely utilised as one of the alternatives besides conventional antimicrobial treatment against vaginal pathogens for the prevention of chronic vaginitis and the restoration of vaginal ecosystem. In addition, the effectiveness of Lactobacillus as prophylaxis has also been well-founded in long-term administration. This review aimed to highlight the beneficial effects of lactobacilli derivatives (i.e. surface-active molecules) with anti-biofilm, antioxidant, pathogen-inhibition, and immunomodulation activities in developing remedies for vaginal infections. We also discuss the current challenges in the implementation of the use of lactobacilli derivatives in promotion of human health. In the current review, we intend to provide insights for the development of lactobacilli derivatives as a complementary or alternative medicine to conventional probiotic therapy in vaginal health.
... Retrieval of 70 articles returned 65 full-text articles with 5 not being able to retrieve. Ultimately, 10 RCTs were included in this review (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Supplementary material 1 showed excluded studies with reasons. ...
Introduction
The evidence for probiotic efficacy in preventing bacterial vaginosis (BV) recurrences among women aged 18 years and above is sparse. We aimed to ascertain the efficacy of probiotics in preventing BV recurrences after at least one menstrual cycle in this population.
Methods
We conducted a systematic literature search using PubMed, MEDLINE (Ovid interface), Web of Science (WoS), Scopus, Embase, ProQuest Dissertations and Theses Global, Cochrane Library databases and registries comprised of Open Science Framework (OSF) preprints registry, the ClinicalTrials.gov (USA), WHO International Clinical Trials Registry Platform (WHO-ICTRP), International Standard RCT Number (ISRCTN) registry, limited to randomized clinical trials (RCTs) in English published between January 2000 and December 2021. The inclusion criteria were trials that administered probiotics to BV-positive women in an experimental arm of at least 20 samples. The usage of probiotics should be preceded with standard antibiotic regimen and followed by a reassessment of BV status after at least a single menstrual cycle. Risk of bias assessment was completed using revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The PROSPERO registration number of the review is CRD42022302044.
Results
From 8,162 identified records, we included 10 studies ( n = 1,234 participants) for final analysis; 7 trials compared probiotics vs. placebo, whereas 3 trials compared probiotics vs. metronidazole alone. Using random-effects meta-analysis, probiotics were shown to reduce the risk of BV recurrences by 45% compared to either placebo or metronidazole [14.8 vs. 25.5%, RR: 0.55 (95%CI: 0.33, 0.91), p = 0.03, I ² = 45.4% (95%CI: 0, 73.7%)]. Sensitivity analysis revealed the robustness of results upon removal of studies with high risk of bias [RR: 0.54 (95%CI: 0.38, 0.77), p = 0.006] and reporting bias (RR: 0.53, 95%CI: 0.39, 0.74, p = 0.002). Meta-regression demonstrated that the route of administration ( p vaginal = 0.67; p oral = 0.44), the total dosage of probiotics ( p = 0.17), cumulative days of probiotic administration ( p = 0.76), and the number of species in probiotic preparation ( p = 0.40) were not linked to BV recurrences.
Interpretation
Probiotics were associated with more than twofold reduction in BV recurrences when BV status was assessed after at least 1-month postintervention. Further high-quality and methodologically standardized RCTs should evaluate probiotic efficacy for BV prevention in a diverse community setting.
Systematic review registration
[ https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290613 ], identifier [CRD42021290613].
... Bacterial vaginosis (BV) is a common infection of the female reproductive tract [1]. Based on Amsel criteria, BV prevalence was up to 8.7% in Beijing (2010), 5.9% in Shandong (2004), and 15.4% in Sichuan (2004) [2]. ...
Gardnerella vaginalis contributes significantly to bacterial vaginosis, which causes an ecological imbalance in vaginal microbiota and presents with the depletion of Lactobacillus sp. Lactobacillus supplementation was reported to be an approach to treat bacterial vaginosis. We investigated the applicability of three Lactobacillus sp. strains (Lactobacillus delbrueckii DM8909, Lactiplantibacillus plantarum ATCC14917, and Lactiplantibacillus plantarum ZX27) based on their probiotic abilities in vitro. The three candidate Lactobacillus sp. strains for bacterial vaginosis therapy showed distinct properties in auto-aggregation ability, hydrophobicity, adhesion to cervical epithelial cells, and survivability in 0.01% hydrogen peroxide. Lpb. plantarum ZX27 showed a higher yield in producing short-chain fatty acids and lactic acid among the three candidate strains, and all three Lactobacillus sp. strains inhibited the growth and adhesion of G. vaginalis. Furthermore, we discovered that the culture supernatant of Lactobacillus sp. exhibited anti-biofilm activity against G. vaginalis. In particular, the Lpb. plantarum ZX27 supernatant treatment decreased the expression of genes related to virulence factors, adhesion, biofilm formation, metabolism, and antimicrobial resistance in biofilm-forming cells and suspended cells. Moreover, Lactobacillus sp. decreased the upregulated expression of interleukin−8 in HeLa cells induced by G. vaginalis or hydrogen peroxide. These results demonstrate the efficacy of Lactobacillus sp. application for treating bacterial vaginosis by limiting the growth, adhesion, biofilm formation, and virulence properties of G. vaginalis.
... Microbial-based therapeutics have recently attracted an increasing amount of interest owing to the beneficial effects to the host health. As pivotal bacteria in the healthy vaginal microbiome, Lactobacillus species can act as antimicrobial adjuvants due to their ability to potentiate the effect of antibiotics (Larsson et al., 2011;Bodean et al., 2013;Recine et al., 2016;Bohbot et al., 2018;Cohen et al., 2020). In 2020, a phase 2b trial (NCT02766023) was conducted on 228 women to assess the efficiency of L. crispatus CTV-05 in preventing BV relapse. ...
The vaginal microbiome is an intricate and dynamic microecosystem that constantly undergoes fluctuations during the female menstrual cycle and the woman’s entire life. A healthy vaginal microbiome is dominated by Lactobacillus which produce various antimicrobial compounds. Bacterial vaginosis (BV) is characterized by the loss or sharp decline in the total number of Lactobacillus and a corresponding marked increase in the concentration of anaerobic microbes. BV is a highly prevalent disorder of the vaginal microbiota among women of reproductive age globally. BV is confirmed to be associated with adverse gynecologic and obstetric outcomes, such as sexually transmitted infections, pelvic inflammatory disease, and preterm birth. Gardnerella vaginalis is the most common microorganism identified from BV. It is the predominant microbe in polymicrobial biofilms that could shelter G. vaginalis and other BV-associated microbes from adverse host environments. Many efforts have been made to increase our understanding of the vaginal microbiome in health and BV. Thus, improved novel and accurate diagnosis and therapeutic strategies for BV have been developed. This review covers the features of vaginal microbiome, BV, BV-associated diseases, and various strategies of diagnosis and treatment of BV, with an emphasis on recent research progresses.
... Probiotic supplementation has recently emerged as a novel biotherapy targeted to the vaginal microbiota (Cohen et al., 2020). Several clinical studies have shown that lactobacilli-containing probiotics are effective adjuncts to antibiotics in treating BV and other infection symptoms, whether administered vaginally or orally (Recine et al., 2016;Bohbot et al., 2018;Cianci et al., 2018;Russo et al., 2018;Cohen et al., 2020;Wijgert et al., 2020). The oral Lactobacillus strains could survival in the gastrointestinal tract and be eliminated from the body with stool, then small amount of Lactobacillus remains at the perianal area could transmission and colonized into the vagina, where it can reproduce in larger quantities (Reid et al., 2001b;Bohbot and Cardot, 2012;Yefet et al., 2020). ...
The purpose of this study was to evaluate the effectiveness of metronidazole and oral probiotics adjunct to metronidazole in the treatment of bacterial vaginosis (BV). One hundred and twenty-six Chinese women with BV were enrolled in this parallel, controlled trial, and were randomly assigned into two study arms: the metronidazole group, which was prescribed metronidazole vaginal suppositories for 7 days, and the adjunctive probiotic group, which received Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 orally for 30 days as an adjunct to metronidazole. Clinical symptoms and Nugent scores at the initial visit, 30 days and 90 days were compared. There was no significant difference of the 30-day total cure rate between the adjunctive probiotic group (57.69%) and the metronidazole group (59.57%), with an odds ratio (OR) of 0.97 (95% confidence interval (CI), 0.70 to 1.35, p-value = 0.04), or of the 90-day total cure rate (36.54% vs. 48.94%, OR, 0.75; 95% CI, 0.47 to 1.19; p-value = 0.213). Also, no significant difference of the vaginal and faecal microbial diversity and structure between the two groups at 0, 30 or 90 days were shown based on 16S rRNA sequences. The probiotic species were rarely detected in either the vaginal microbiota or the faecal microbiota after administration which may revealed the cause of noneffective of oral probiotics. No serious adverse effects were reported in the trial. The study indicated that oral probiotic adjunctive treatment did not increase the cure rate of Chinese BV patients compared to metronidazole.
... Early evidence of soil transplantation date back to the 1930s and 1940s, with studies concerning suppressive soils. The transferability of disease suppression was elegantly demonstrated by the addition of small amounts of suppressive soil, ranging from less than 1% to 10% (w/w), to a disease-conducive soil which rapidly leads, as a consequence, to the transfer of the capability to control the disease [111]. The use of a small amount of soil rules out the possibility that changes in soil chemistry (e.g., pH, organic carbon, nitrogen, etc.) could be the causes of disease suppression. ...
Both soil and the human gut support vast microbial biodiversity, in which the microbiota plays critical roles in regulating harmful organisms. However, the functional link between microbi-ota taxonomic compositions and disease suppression has not been explained yet. Here, we provide an overview of pathogen regulation in soil and mammals gut, highlighting the differences and the similarities between the two systems. First, we provide a review of the ecological mechanisms underlying the regulation of soil and pathogens, as well as the link between disease suppression and soil health. Particular emphasis is thus given to clarifying how soil and the gut microbiota are associated with organic amendment and the human diet, respectively. Moreover, we provide several insights into the importance of organic amendment and diet composition in shaping beneficial mi-crobiota as an efficient way to support crop productivity and human health. This review also discusses novel ways to functionally characterize organic amendments and the proper operational combining of such materials with beneficial microbes for stirring suppressive microbiota against pathogens. Furthermore, specific examples are given to describe how agricultural management practices, including the use of antibiotics and fumigants, hinder disease suppression by disrupting microbiota structure, and the potentiality of entire microbiome transplant. We conclude by discussing general strategies to promote soil microbiota biodiversity, the connection with plant yield and health, and their possible integration through a "One Health" framework.
... Generally, since vaginal dysbiosis and other gynaecological infections are generally characterised by a reduction in vaginal lactobacilli content, the administration of probiotics, especially lactobacilli, has been proposed as a valid treatment for vaginal disorders. In fact, a wide literature reports that the administration of probiotics is able to restore the normal vaginal microbiota [53][54][55][56]. Beside the vaginal application, a wide literature shows that probiotic bacteria can be administered orally, also through foods, due to their ability to pass from the intestine to the vagina, with a consequent beneficial impact on the vaginal habitat [37-41]. ...
This research is aimed to evaluate the suitability of Squacquerone cheese to support the viability of Lactobacillus crispatus BC4, a vaginal strain endowed with a strong antimicrobial activity against urogenital pathogens and foodborne microorganisms, in order to recommend a gender food for woman wellbeing. The viability of L. crispatus BC4, used as adjunct culture, was evaluated during the refrigerated storage of Squacquerone cheese, as well as when the cheese was subjected to simulated stomach-duodenum passage tested by the patented Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Moreover, the effects of L. crispatus BC4 addition were evaluated on product hydrolytic patterns, in terms of proteolysis, lipolysis and volatile molecule profiles. The data showed that L. crispatus BC4 maintained high viability, also in presence of physiological stress conditions, until the end of the refrigerated storage. Moreover, the inclusion of L. crispatus BC4 gave rise to cheese product with higher score of overall acceptability when compared to control cheese. In addition, the survival of L. crispatus BC4, carried in test cheese, in gastro intestinal conditions was confirmed by SHIME. The results showed that the vaginal Lactobacillus strain was more affected by the low pH of the stomach, simulated by the SHIME reactor, rather than to bile salts and pancreatic juices. Although only in vivo trials will be able to confirm the functionality of the cheese in the vaginal environment, these data represent a first step towards the employment of the Squacquerone cheese as probiotic food able to promote the woman’s health by preventing gynaecological infections.
... Other options to repress the growth of anaerobes associated with bacterial vaginosis and/or support the growth of Lactobacilli include estrogen, lactic acid, or boric acid to lower pH [69][70][71]. Some authors recommend the use of probiotics to modulate the vaginal microbiome, either after antibiotic treatment or as primary therapy [72]. A possible outlook into the future represents the transplantation of the vaginal microbiome in patients with refractory bacterial vaginosis [73]. ...
The human microbiome has been given increasing importance in recent years. The establishment of sequencing-based technology has made it possible to identify a large number of bacterial species that were previously beyond the scope of culture-based technologies. Just as microbiome diagnostics has emerged as a major point of focus in science, reproductive medicine has developed into a subject of avid interest, particularly with regard to causal research and treatment options for implantation failure. Thus, the vaginal microbiome is discussed as a factor influencing infertility and a promising target for treatment options. The present review provides an overview of current research concerning the impact of the vaginal microbiome on the outcome of reproductive measures. A non-Lactobacillus-dominated microbiome was shown to be associated with dysbiosis, possibly even bacterial vaginosis. This imbalance has a negative impact on implantation rates in assisted reproductive technologies and may also be responsible for habitual abortions. Screening of the microbiome in conjunction with antibiotic and/or probiotic treatment appears to be one way of improving pregnancy outcomes.
... Lactobacillus is the dominant bacterial genus in the community, helping to maintain microbial homeostasis in the vagina [96]. When the abundance of Lactobacillus decreases, the resulting increase in anaerobic and pathogenic bacteria in the micromicrobiota results in an unbalanced vaginal microbiota, causing bacterial vaginosis (BV) [97]. BV is treated most frequently with antibiotics, but the misuse of antibiotics can lead to the accumulation and spread of antibiotic-resistant genes, leading to the development of drug-resistant bacteria [98]. ...
The probiotics market is one of the fastest growing segments of the food industry as there is growing scientific evidence of the positive health effects of probiotics on consumers. Currently, there are various forms of probiotic products and they can be categorized according to dosage form and the site of action. To increase the effectiveness of probiotic preparations, they need to be specifically designed so they can target different sites, such as the oral, upper respiratory or gastrointestinal tracts. Here we review the characteristics of different dosage forms of probiotics and discuss methods to improve their bioavailability in detail, in the hope that this article will provide a reference for the development of probiotic products.
Bacterial vaginosis (BV) is a common but treatable condition, with a number of effective available treatments, including oral and intravaginal metronidazole and clindamycin and oral tinidazole. However, as many as 50% of women with BV experience recurrence within 1 year of treatment for incident disease. Some reasons for recurrence include the persistence of residual infection, resistance, and possibly reinfection from either male or female partners. Persistence may occur due to the formation of a biofilm that protects BV-causing bacteria from antimicrobial therapy. Poor adherence to treatment among patients with genitourinary infections may lead to resistance. However, the underlying mechanisms of recurrent etiology of BV are not known. Recommended treatment for recurrent BV consists of an extended course of metronidazole treatment (500 mg twice daily for 10-14 days); if ineffective, metronidazole vaginal gel 0.75% for 10 days, followed by two times per week for 3-6 months, is an alternate treatment regimen. Past studies of clindamycin and tinidazole in the treatment of recurrent BV have focused on patients with evidence of metronidazole resistance. Secnidazole may be an attractive new option due to one-time dosing. Initial studies on biofilm disruption, use of probiotics and prebiotics, and botanical treatments have shown some promise, but must be studied further before use in the clinic. Despite limitations, antimicrobial therapy will remain the mainstay of treatment for recurrent BV for the foreseeable future.
Bacterial vaginosis is a prevalent vaginal infection that affects women of all ages. Presenting symptoms include a vaginal discharge that is thin and white and has a fishy odor. This infection is associated with the acquisition of other sexually transmitted infections as well as premature labor and preterm birth. Recurrence rates after treatment are high, and medication adverse effects are common, leading many women to seek alternative therapies to manage and prevent recurrence. Many of these treatments are searchable online, and ingredients are easily obtainable. The purpose of this article is to review the state of the science regarding the safety and efficacy of alternative therapies for the treatment of bacterial vaginosis in nonpregnant women.
We report the results of a first exploratory study testing the use of vaginal microbiome transplantation (VMT) from healthy donors as a therapeutic alternative for patients suffering from symptomatic, intractable and recurrent bacterial vaginosis (ClinicalTrials.gov NCT02236429). In our case series, five patients were treated, and in four of them VMT was associated with full long-term remission until the end of follow-up at 5–21 months after VMT, defined as marked improvement of symptoms, Amsel criteria, microscopic vaginal fluid appearance and reconstitution of a Lactobacillus-dominated vaginal microbiome. One patient presented with incomplete remission in clinical and laboratory features. No adverse effects were observed in any of the five women. Notably, remission in three patients necessitated repeated VMT, including a donor change in one patient, to elicit a long-standing clinical response. The therapeutic efficacy of VMT in women with intractable and recurrent bacterial vaginosis should be further determined in randomized, placebo-controlled clinical trials.
Purpose:
Oral metronidazole therapy is the standard of care for bacterial vaginosis (BV), yet it has alarming rates of recurrence and refractory responses among recurrent BV (RBV) patients. This study addresses whether high dose vaginal metronidazole therapy (HDM) is beneficial in RBV patients who fail after standard of care (SOC) therapy, whether diagnostic test scores proximal to the HDM predict clinical outcome, and whether menses, coitus, or race influences therapy outcome.
Patients and methods:
A total of 90 patients with RBV were given SOC and tracked 74 for up to 9 months. Refractory or recurrent patients (57) with symptomatic BV were given HDM and followed for up to 8 months. Patients were evaluated by Amsel criteria, Nugent score, and a qPCR assay that assesses the Lactobacillus content.
Results:
HDM achieved at least short-term remission in 68% of the patients who were refractory to or recurred after SOC and provided a 10-day increase in the mean duration of remission among patients who eventually recurred (p=0.027). Patients with prolonged dysbiosis (pH >5 or Amsel 4) before symptomatic recurrence were more likely to recur after subsequent HDM. Most recurrence happened within 10 days of menses, but sex in this cohort was not associated with clinical outcome. Mean diagnostic BV scores of African American patients in remission were inferior to scores of a small cohort of Caucasian patients in remission.
Conclusion:
Encouraging results obtained with HDM justify a prospective, randomized study to determine if follow-up HDM is beneficial among a broader cohort of women failing conventional oral metronidazole therapy.
Bacterial vaginosis (BV) is the most common cause of vaginal discomfort in women. It is characterised by abnormal vaginal microbiota with a depletion of lactobacilli and predominance of anaerobic microorganisms, mainly Gardnerella vaginalis and Atopobium vaginae. Although antibiotics represent an effective therapeutic option in the short-term, recurrent infections still remain a serious problem. Nowadays, evidence exists about the efficacy of probiotics for the management of BV. The aim of the current double blind, randomised clinical trial was to assess the efficacy of a probiotic mixture, including Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001, in combination with bovine lactoferrin, as adjuvant therapy to metronidazole in women with recurrent BV. In particular, normalisation of Nugent score, remission of symptoms and recurrences during a six-months follow-up were assessed. 48 adult women received metronidazole (500 mg twice daily) for 7 days and randomly assigned to take simultaneously either probiotics plus lactoferrin or placebo (2 capsules/day for 5 days followed by 1 capsule/day for 10 consecutive days; induction phase). The verum or placebo administration (1 capsule/day for 10 consecutive days) was repeated each month (maintenance phase) during the six months of follow-up starting the first day of menstrual cycle since the menstrual blood increases the vaginal pH and contributes to increase the risk of recurrences. The results showed that symptoms (vaginal discharge and itching), Nugent score and recurrence rate were significantly improved by probiotics mixture in association with lactoferrin. This alternative approach may represent a safe and effective remedy for the restoration of healthy vaginal microbiota in preventing recurrent BV.
Objective:
The aim of the study was to explore a role of oral intake of a mixture of 3 Lactobacillus species in recurrence of bacterial vaginosis (BV).
Materials and methods:
A phase 2 randomized parallel group prospective placebo-controlled study conducted at 7 clinical centers enrolled 18- to 45-years-old women with recent symptomatic BV cured with metronidazole. Within 48 hours after completion of metronidazole therapy, eligible women received 1 capsule of the verum (5.4 billion Lactobacillus crispatus LMG S-29995, Lactobacillus brevis, and Lactobacillus acidophilus in proportion of 60%, 20%, and 20%, respectively), or the placebo supplement 2 times daily for the first 7 days and 1 time daily for the next 8 to 120 days. The primary outcome measure was the percentage of recurrence of BV, which was defined as 3 of 4 Amsel criteria plus abnormal vaginal discharge/vulvar odor during 4 months of intake of the test dietary supplement. Differences between the groups were assessed with Z test for proportions.
Results:
One hundred sixty-six women were analyzed in the verum (82 patients) and the placebo group (82 patients). Recurrence of BV was documented in 15 (18.3%) of 82 women in the verum group and 27 (32.1%) of 84 in the placebo group (p = .014). Rates of survival without BV rates were higher in the verum group (Cox F test, p = .018). Both verum and placebo supplements were well tolerated.
Conclusions:
Oral intake of L. crispatus LMG S-29995, L. brevis, and L. acidophilus can significantly decrease percent of recurrences of BV in recently treated women and prolong time to recurrence of the disease.
Introduction
Bacterial Vaginosis (BV) is the most common cause of vaginal discharge. However, in some cases, side effects and resistance rates have been reported when antibiotics are administered. This problem has prompted several investigations on the administration of probiotics as an adjunct therapy to treat this infection.
Objection
This study aims to conduct a meta-analysis based on evidence to determine the efficacy and safety of probiotic and antibiotic treatments.
Methods
The meta-analysis was performed using PRISMA guidelines. The literature review was conducted in December 2020 using PubMed, Science Direct, Cochrane Library, and RevMan V.5.3.
Result
The results showed a high and significant cure rate from the analysis of 1006 and 528 samples of probiotics and non-probiotics or control in 16 studies. The recurrence rate was statistically significant with probiotic treatment. Furthermore, neither procedures nor therapy failure showed a significantly lower adverse event rate than the control group.
Conclusion
Probiotic shows better results compared to the control group. However, both have the same occurrence of adverse event.
La vaginose bactérienne correspond à un déséquilibre du microbiote vaginal. Bien que les mécanismes en jeu ne soient pas encore parfaitement élucidés, il est possible, pour le pharmacien d’officine, d’accompagner ses patientes dans le diagnostic, la prise en charge et la prévention de cette pathologie.
Lactobacillus crispatus colonizes the human feces, human vagina, and the crops and ceca of chicken. To explore the genetic characteristics and evolutionary relationships of L. crispatus isolated from different niches, we selected 37 strains isolated from the human vagina (n = 17), human feces (n = 11), and chicken feces (n = 9), and used comparative genomics to explore the genetic information of L. crispatus from the feces and vagina. No significant difference was found in the three sources of genomic features such as genome size, GC content, and number of protein coding sequences (CDS). However, in a phylogenetic tree constructed based on core genes, vagina-derived L. crispatus and feces-derived strains were each clustered separately. Therefore, the niche exerted an important impact on the evolution of L. crispatus. According to gene annotation, the L. crispatus derived from the vagina possessed a high abundance of genes related to acid tolerance, redox reactions, pullulanase, and carbohydrate-binding modules (CBMs). These genes helped L. crispatus to better adapt to the acidic environment of the vagina and obtain more nutrients, maintaining its dominance in the vagina in competition with other strains. In feces-derived bacteria, more genes encoding CRISPR/Cas system, glycoside hydrolases (GHs) family, and tetracycline/lincomycin resistance genes were found to adapt to the complex intestinal environment. This study highlights the evolutionary relationship of L. crispatus strains isolated from the vagina and feces, and the adaptation of L. crispatus to the host environment.
Purpose:
Bacterial vaginosis (BV) is one of the most common vaginal complaints of women of reproductive age, characterized by a shift from a Lactobacillus-dominated vaginal microbiome towards a more diverse flora of facultative and obligately anaerobic bacteria. BV can increase the risk of preterm births, contracting sexually transmitted infections and developing other chronic health issues. Standard treatment for BV are antibiotics, however despite initial efficacy, they do not provide effective long-term treatment and recurrence or persistence prevention. This systematic review focuses on describing the current study situation and summarizing the newest data on the efficacy of alternative non-antibiotic options, namely probiotic products containing lactobacilli, lactic acid, sucrose gel, combination products with estriol, and supplementation of antibiotics.
Methods:
We conducted a systematic literature search using the MEDLINE database and evaluated the 33 trials which met our inclusion criteria.
Conclusion:
The diverse study designs produced extremely varied outcomes, but so far the results are promising. Furthermore, these alternatives have shown little to no adverse effects and are consequently generally considered safe to use. In general, the results of this review warrant more thorough trials with larger cohort sizes to provide sufficient evidence for these alternatives to be a part of official treatment recommendations.
Multiple studies have shown that oral or vaginal probiotics can effectively treat and prevent recurrent bacterial vaginosis. The dose, route, and treatment protocols vary greatly between studies, but many have shown a statistically significant reduction in the rate of recurrence of bacterial vaginosis. Further research is needed to determine the adequate dose, specific probiotic, optimal duration, and route of administration, with or without antibiotics.
Bacterial vaginosis (BV) is a common vaginal dysbiosis in women of reproductive age. However, the cure rate for BV varies considerably and many women experience a relapse after the initial treatment. The present meta-analysis aimed to evaluate the clinical cure rates (CCRs) in randomized controlled trials (RCTs) through different therapies and administration routes. This meta-analysis included a final set of 25 eligible studies with a total of 57 RCTs and compared the effectiveness of BV treatments among non-pregnant and pregnant women. The initial range of CCRs varied greatly from 46.75% to 96.20% and the final pooled CCR was 75.5% (CI: 69.4–80.8) using the random model. The heterogeneity indices were Q = 418.91, I2 = 94.27%, and τ = 0.7498 (p < 0.0001). No publication bias was observed according to Funnel plot symmetry and Egger’s linear regression test (p = 0.1097). To evaluate different variables, sub-group analysis, meta-regressions, and network meta-analysis were also realized. The highest P-scores in CCR were obtained by: (1) a combined therapy with local probiotic treatment and application of antibiotics by both administration route (oral clindamycin and local 5-nitroimidazole; P-score = 0.92); (2) a combined therapy with oral administration of 5-nitroimidazole and probiotic treatment (P-score = 0.82); (3) and a combined therapy with local administration of 5-nitroimidazole and oral probiotic treatment (P-score = 0.68). A clear-cut decision of the best BV treatment was not possible due to the heterogeneity of outcomes reported in the trials, indicating the necessity for a better characterization of RCTs. Finally, combined therapies suggested the reduction of the optimal concentration of antibiotics, and double phase treatments of antibiotics indicated an increment of CCRs in BV.
Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. The conventional antibiotic treatment can aggravate microbial dysbiosis, alter the acid environment of the vagina and lead to drug resistance, thus shows low cure rate and high recurrence rate. This poses significant physiological and psychological burden to the BV patients. Vaginal microbiota transplantation (VMT) is a novel live biotherapeutic approach. It directly engrafts the whole vaginal microbiota from healthy women to the vaginal tract of patients to rapidly reconstruct the vaginal microbiota environment and restore the vaginal health. This article summarizes the development, present challenges, and future directions of using VMT, with the aim to explore new strategies for treatment of BV and promote the clinical use of VMT.
Cada vez es más frecuente la administración de Lactobacillus en la clínica. Por su versatilidad y aparente inocuidad se ha diversificado la administración de éstos para tratar pacientes con enfermedades infecciosas, síndrome de intestino irritable, alergias y cáncer. Este artículo tiene como objetivo revisar el estado de arte de la eficacia de la administración de Lactobacillus en ensayos clínicos controlados. Se revisaron en la base MEDLINE los ensayos clínicos en humanos publicados entre enero de 2016 y el 12 de junio de 2019. Se revisaron 348 artículos, de los que se descartaron los que utilizaran mezclas con otros probióticos que no fueran Lactobacillus, obteniéndose un total de 74 artículos. Entre los ensayos clínicos revisados, en el 74% resultó eficaz la administración de Lactobacillus. PALABRAS CLAVE: Lactobacillus; microbiota; enfermedades infecciosas; síndrome de intestino irritable; alergias; cáncer. Abstract The use of Lactobacillus in the clinic is becoming more common. Because of their versatility and apparent safety, the use of these has diversified to treat patients with infectious diseases, irritable bowel syndrome, allergies and cancer. This article aims to review the state of art on the efficacy with the use of Lactobacillus in controlled clinical trials. Human clinical trials published between January 2016 and June 12, 2019 were reviewed at the MEDLINE database. A total of 348 articles were reviewed, of which those using mixtures with other probiotics other than Lactobacillus were discarded, resulting in a total of 74 articles. Among 74 articles reviewed, efficacy was statistically demonstrated in 74% of them.
Rampant use of antibiotics in human and veterinary medicine with the paucity in the discovery of novel antibiotics has pushed the clinically relevant microbes to develop long-term and indeed a never-ending threat of antimicrobial resistance. As a result, the infections pertinent to gastrointestinal, pulmonary/air-way, and urogenital tract are posing a real challenge to cure by conventional antibiotics. As more antibiotics are rendered ineffective to curb infectious diseases, it is crucial to unravel novel antimicrobials to fight against resistant infections. Today, several advanced strategies, such as antimicrobial peptides, bacteriophages, endolysins, nanoparticles, engineered peptides, antibodies, and probiotics, have been put forth by the scientific community to combat difficult-to-treat-infections with antibiotics. Amidst the several alternatives to antibiotics, the present chapter aims to highlight the role of probiotics in confronting antibiotic-resistant pathogens due to their multifaceted inhibitory action on pathogenic microbes. Probiotic-based remedial approach targets both pathogens (superbug) and host. The mechanisms of actions of probiotics against multidrug superbugs largely remain multifarious. The protective mode of probiotics against such infections is mediated by various antagonistic activities, such as antimicrobial, antibiofilm, antivirulence, antiquorum sensing, antiinvasive, antiadhesive, and antidrug resistance. Besides strengthening the epithelial barrier functioning, probiotics strengthen the host immune system by priming the immune cells to fight against superbugs. Owing to these beneficial effects, probiotics intervention through intragastric, intravaginal, and intranasal routes are widely evaluated as a promising strategy to curb the resistant infections of intestinal, urogenital/vaginal, and respiratory infections caused by antibiotic-resistant pathogens. In this context, the present chapter recapitulates the mechanism of action of probiotics while antagonizing the multidrug-resistant superbugs and their subsequent infections.
The human vaginal microbiota is a critical determinant of vaginal health. These communities live in close association with the vaginal epithelium and rely on host tissues for resources. Although often dominated by lactobacilli, the vaginal microbiota is also frequently composed of a collection of facultative and obligate anaerobes. The prevalence of these communities with a paucity of Lactobacillus species varies among women, and epidemiological studies have associated them with an increased risk of adverse health outcomes. The mechanisms that drive these associations have yet to be described in detail, with few studies establishing causative relationships. Here, we review our current understanding of the vaginal microbiota and its connection with host health. We centre our discussion around the biology of the vaginal microbiota when Lactobacillus species are dominant versus when they are not, including host factors that are implicated in shaping these microbial communities and the resulting adverse health outcomes. We discuss current approaches to modulate the vaginal microbiota, including probiotics and vaginal microbiome transplants, and argue that new model systems of the cervicovaginal environment that incorporate the vaginal microbiota are needed to progress from association to mechanism and this will prove invaluable for future research. This Review summarizes current knowledge on the vaginal microbiota and discusses how research can progress from association to mechanism to provide deeper insights into its role in health and disease.
The vagina endures multifaceted changes from neonatal to menopausal phases due to hormonal flux, metabolite deposition, and microbial colonization. These features have important implications in women's health. Several pre-factors show dynamic characteristics according to the phases that shift the vaginal microbiota from anaerobes to aerobes which is a hallmark of healthy vaginal environment. These factors include oestrogen levels, glycogen deposition, and vaginal microstructure. In the adult phase, Lactobacillus is highly dominant and regulates pH, adherence, aggregation, immune modulation, synthesis of bacteriocins, and biosurfactants (BSs) which are antagonistic to pathogens. Maternal factors are protective by favouring the colonization of lactobacilli in the vagina in the neonatal phase, which diminishes with age. The dominance of lactobacilli and dysbiosis in the adult phase depends on intrinsic and extrinsic factors in women, which vary between ethnicities. Recent developments in probiotics used against vaginal microbiome dysbiosis have shown great promise in restoring the normal microbiota including preventing the loss of beneficial bacteria. However, further in-depth studies are warranted to ensure long-term protection by probiotics. This review highlights various aspects of the vaginal microenvironment in different phases of growth and diverse ethnicities. Furthermore, it discusses future trends for formulating more effective population-specific probiotics and implications of paraprobiotics and postbiotics as effective therapeutics.
Problem
The functions of vaginal lactobacilli in susceptibility to infectious diseases as regards epithelial barrier integrity and wound healing remain incompletely understood.
Method of study
Lactobacillus crispatus, one of the most common Lactobacillus species in the vagina and among the most protective against sexually transmitted infections, was cocultured with an immortalized human vaginal epithelial cell line (MS74), and a scratch assay was performed to evaluate re‐epithelialization. The concentration of vascular endothelial growth factor A (VEGF) was measured using enzyme‐linked immunosorbent assay (ELISA). An immunofluorescence assay was performed to locate the expression of VEGF and VEGF receptor (VEGFR) 1 and 2. The effects of the bacterial supernatant of L. crispatus were also evaluated.
Results
Lactobacillus crispatus significantly accelerated re‐epithelialization of MS74 cells, accompanied by an increase in VEGF concentration. In contrast, heat‐killed L. crispatus did not show this effect. The bacterial supernatant of L. crispatus also induced re‐epithelialization. The immunoreactivity of VEGF was higher at the scratched edge, whereas VEGFR1 and 2 stained site‐independently. Recombinant VEGF induced cell migration in a dose‐dependent manner. The bacterial supernatant of L. crispatus also significantly accelerated re‐epithelialization in MS74 cells and increased the concentration of VEGF in the culture 24 hours after the scratch.
Conclusion
These results may enhance our knowledge of the importance of L. crispatus in the healing of damaged vaginal epithelium and protection against the consequent risk of pathogenic infections, such as human immunodeficiency virus (HIV), and improve our understanding of vaginal epithelial barrier integrity maintenance by this bacterium.
Background
Bacterial vaginosis (BV) during pregnancy is a well-established risk factor for preterm birth and other preterm pregnancy complications. Little is known about adverse neonatal outcomes associated with BV exposure in full-term births, nor its influence on adverse outcomes independent of its effect on gestational age. The purpose of this study was to examine the relationship between BV during pregnancy and adverse neonatal outcomes among full-term and preterm infants.
Methods
We conducted a retrospective cohort study of Washington State mother/infant pairs from 2003-2013, stratified by full-term (primary outcomes) and preterm births (secondary outcomes). BV-exposed and unexposed women were frequency-matched based on year of delivery. BV exposure and adverse outcomes [assisted ventilation/respiratory distress, neonatal intensive care unit (NICU) admission, neonatal sepsis, fetal mortality, and infant mortality] were identified using birth certificates, ICD-9 codes from linked hospital records, and death certificates. Associations between BV exposure and outcomes were assessed using multivariable Poisson regression, adjusted for maternal demographics, gestational age, and other pregnancy complications, including infections.
Results
A total of 12,340 mother/infant pairs were included: 2,468 BV-exposed (2198 term, 267 preterm) and 9,872 BV unexposed (9156 term, 708 preterm). Among full-term infants, BV-exposed mothers were younger, more likely to be Black or Hispanic, more likely to have had a sexually transmitted infection, and less likely to have a college degree than unexposed mothers. Term BV exposed infants were more likely to have meconium at delivery. Following adjustment, BV was associated with an increased risk of assisted ventilation/respiratory distress at birth (aRR = 1.28, 95 % CI 1.02-1.61), NICU admission (aRR = 1.42, 95 % CI 1.11-1.82), and neonatal sepsis (aRR = 1.60, 95 % CI 1.13-2.27) among full-term infants. These associations were independent of the presence of chorioamnionitis or meconium. Among preterm infants, BV-exposure was associated with an increased risk for NICU admissions only (aRR = 1.24, 95 % CI 1.04-1.46).
Conclusions
BV exposure during pregnancy is associated with adverse neonatal outcomes even among infants born full-term. These findings amongst full-term infants are novel, and highlight neonatal implications of BV in pregnancy independent of BV’s effect on preterm birth.
The aim of this study was to estimate the risk factors of bacterial vaginosis (BV) among rural married women of childbearing age in Anhui Province of China. A cross-sectional study was conducted and the method of stratified cluster sampling was used to identify a sample of 53,652 married women aged 18-49 years. All women were asked to complete an interviewer-administered standardized questionnaire, covering sociodemographic characteristics, history of menstruation, marriage and procreation, sexual life, personal hygienic behaviors, and reproductive tract infections (RTIs) knowledge, followed by the gynecological examination and laboratory inspection. A total of 53,286 married women aged 18-49 years were included in this analysis. The prevalence of BV was 11.99 % (6,391/53,286). Risk factors for BV included the minority nationality, women's lower education levels, husband's elder age, over 35 days of menstrual cycle, less than 3 days of menstruation, dysmenorrhea, usage of an intrauterine device (IUD), lack of RTIs knowledge, higher frequency of washing genitals before having sex with husband and changing underwear, lower frequency of sexual intercourse per month, and suffering from other RTIs. The results suggest that BV can be affected by many factors among rural married women of reproductive age, so comprehensive, scheduled programs at healthcare educations should be provided for women in order to prevent BV.
The purpose of this study was to investigate how human vaginal isolates of Lactobacillus acidophilus, Lactobacillus jensenii, Lactobacillus gasseri and Lactobacillus crispatus inhibit the vaginosis-associated pathogens Gardnerella vaginalis and Prevotella bivia. Results show that all the strains in coculture condition reduced the viability of G. vaginalis and P. bivia, but with differing degrees of efficacy. The treatment of G. vaginalis- and P. bivia-infected cultured human cervix epithelial HeLa cells with L. gasseri strain KS120.1 culture or cell-free culture supernatant (CFCS) results in the killing of the pathogens that are adhering to the cells. The mechanism of the killing activity is not attributable to low pH and the presence of lactic acid alone, but rather to the presence of hydrogen peroxide and proteolytic enzyme-resistant compound(s) present in the CFCSs. In addition, coculture of G. vaginalis or P. bivia with L. gasseri KS120.1 culture or KS120.1 bacteria results in inhibition of the adhesion of the pathogens onto HeLa cells.