Article

Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence

Authors:
  • institute fournier
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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.

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... Altogether 17 studies were excluded for the following reasons: three studies did not report data on the outcome(s) of interest [15,16,19], two studies were shown to be non-RCTs [20,21], one study was considered to be a duplication of a former publication [22], seven studies introduced unqualified experimental interventions such as oral probiotics [23][24][25][26][27] and complementary medicine [28], two studies focused on ineligible participants (vaginal infections instead of BV) [29,30], and two studies did not provide adequate data and did not reply to our inquiry emails [31,32]. Finally, 11 studies were included [33][34][35][36][37][38][39][40][41][42][43]. We also screened the reference lists of included studies, which located 38 trials. ...
... The sample size of the included studies ranged from 30 in South Africa [36] to 450 in Australia [33]. Two studies were three-armed [33,37]; others were two-armed [34][35][36][38][39][40][41][42][43]. ...
... Five studies compared antibiotics plus probiotics administered sequentially vs antibiotics plus placebo administered sequentially [33][34][35]40,41]. Four studies compared antibiotics plus probiotics administered sequentially vs antibiotics only [36][37][38][39]. ...
Article
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The objective was to examine the pooled effects of antibiotic–probiotic combinations by examining the cure rate and recurrence rate for bacterial vaginosis (BV). A systematic literature search was conducted from electronic databases. All parallel randomized controlled trials (RCTs) that focused on the effects of antibiotics combined with intravaginal probiotics were included. Cure rate and recurrence rate were the primary and secondary outcomes to be analyzed. Meta-analysis was conducted following the Cochrane handbook for Systematic Reviews of Interventions. As a result, of 923 studies identified, 11 articles involving 1,493 BV patients met the inclusion criteria and nine were available for meta-analysis. A meta-analysis of two studies evaluated the recurrence rate 12–16 weeks after treatment. Results showed a statistically significant difference favoring the antibiotics plus probiotics group vs the antibiotics plus placebo group (relative risk 0.62, 95% confidence interval [CI]: 0.45–0.85). The narrative review in one study indicated that the cure rate was higher in the antibiotics plus probiotics group, giving a significant HR ratio of 0.73 (95% CI 0.54–0.98) (p = 0.042). In conclusion, vaginal application of Lactobacillus in combination with antibiotics for the treatment of BV could be a promising method for both reducing the recurrence rate and relieving symptoms of BV.
... Published between 2006 and 2021, the five studies included 425 adult female patients with BV; the main characteristics are presented in Table 1 (Ref. [39,[43][44][45][46]). Two studies were conducted in Africa, two in Europe and one in China. ...
... The treatment results of all included RCTs are shown in Table 2 (Ref. [39,[43][44][45][46]). The pooled results from the random-effects model combining the RR for the recurrence rate of BV are shown in Fig. 4 (Ref. ...
... The pooled results from the random-effects model combining the RR for the recurrence rate of BV are shown in Fig. 4 (Ref. [39,[43][44][45][46]). The combined results of the five studies show that probiotics supplementation or treatment alone can significantly reduce the recurrence rate of BV in adult female patients (RR 0.35; 95% CI 0.11-1.14). ...
Article
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Background The purpose of this meta-analysis was to assess the value of probiotics in the treatment of adult female bacterial vaginosis (BV). Methods We looked for published randomized controlled trials in PubMed, Embase and The Cochrane Library from the inception dates of the database to January 3rd, 2022. We conducted the search focusing on the treatment of adult female BV with probiotics. Two independent researchers screened the literature, evaluated the trial quality and extracted the data according to the inclusion and exclusion criteria. The primary outcome was the ratio of patients with BV with recurrence according to Nugent score 7–10 for recurrence after treatment. After heterogeneity was assessed using Review Manager 5.4 software, meta-analysis and bias assessment were performed using Stata 17.0 software. Results A total of 5 articles representing 425 patients were included in this meta-analysis. Compared with antibiotics alone or antibiotics combined with a placebo, probiotics or probiotics combined with antibiotics significantly reduced the rate of recurrence at around the 30th day (risk ratio (RR) 0.11; 95 % confidence interval (CI) 0.03–0.33). However, in the analysis of heterogeneity, we found that after 30 days, the therapeutic effect of probiotics decreased with the extension of follow-up time (RR 0.50; 95% CI 0.24–1.03), (RR 1.24; 95% CI 0.88–1.76). Conclusions The short-term efficacy of probiotics in the treatment of BV in adult female patients may be satisfactory, but the long-term efficacy of probiotic therapy may be suboptimal and still requires validation by further clinical trials.
... Женщинам с БВ, у которых прежде наблюдалось не менее двух случаев возвратного течения БВ, назначали стандартный курс лечения (метронидазол, 1 г per os в день в течение 7 дней), после которого они ежедневно принимали пробиотик Physioflor1 (Lactobacillus crispatus IP174178, 10 9 КОЕ) вагинально, в капсулах, в течение четырех менструальных циклов. Число возвратных случаев БВ за 4 месяца приема пробиотика составило 20,5 % по сравнению с группой плацебо -41 % [79]. ...
... Анализируя ряд проведенных ранее клинических испытаний, часть авторов приходит к выводу, что лечение БВ пробиотиками, в том числе при их совместном применении с антибиотиками, при несомненном краткосрочном эффекте, вызывает сомнения при рассмотрении долгосрочного эффекта [82][83][84]. Действительно, ни один из испытываемых в последние годы пробиотиков не показал эффективность, приближающуюся к 100 % [78, 79,81,85,86]. Очевидно, снижение эффективности пробиотиков в отдаленные сроки после начала лечения может быть связано с их вытеснением представителями «местной» вагинальной микрофлоры, а также, возможно, бактериями, проникающими в вагину из кишечника. Также становится понятным, что лечение возвратного БВ с применением пробиотиков, эффективное у одних женщин и безуспешное у других, требует персонифицированного подхода. ...
Article
The review presents data on the etiology and treatment of bacterial vaginosis. Bacterial vaginosis is caused by the replacement of a protective microbiota in a lower part of a female reproductive tract with the pathogenic one. This disease is widespread in a world, in some cases it is asymptomatic, but is accompanied by complications, which include chorioamnionitis, inflammatory diseases of the pelvic organs, cervicitis, premature birth. In some cases, the disease is characterized by a recurrent course that requires a personalized treatment.
... For the bile salt hydrolysis test, fresh cultures were streaked onto MRS agar plates containing 0.5% (w/v) taurodeoxycholic acid. The hydrolysis effect was indicated by different colony morphology (partial hydrolysis recorded as 1) from the control MRS plates, after 48 h of anaerobic incubation at 37 °C [17]. ...
... Previous studies have shown that probiotics improve immune responses, stool consistency and the density of vaginal Lactobacillus [24,25]. Probiotics applied to the vagina have good e cacy, but oral administration is more convenient [17]. Thus, we investigate the survival of the 4 selected vaginal Lactobacillus strains not only in the simulated vaginal uid (SVF) but also in simulated gastric juice (SGJ) and simulated intestinal uid (SIF), in order to select promising Lactobacillus strains to be used both as vaginal capsules and dietary supplements. ...
Preprint
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Lactobacillus iners is often associated with vaginal dysbiosis and bacterial vaginosis (BV), which are risk factors for adverse gynecological and obstetric outcomes. Lactobacillus strains from the vagina of healthy women were screened for inhibitory activity against L. iners. Four active strains were identified, whereby L. gasseri H87 exhibited the highest inhibitory activity against L. iners , followed by L. rhamnosus H23. All four strains inhibited the growth of potential pathogens of the gastrointestinal, urogenital and reproductive tract, and were capable of co-aggregating with the cells of the tested pathogens to varying degrees. H23 and H78 were viable under in vitro conditions simulating the vaginal, gastric and intestinal environment, with survival rates > 80%. The four strains exhibited good auto-aggregation of more than 30%. H23 and H87 also exhibited good co-aggregation with Listeria monocytogenes and Esch e richia coli , with values of more than 30%. Safety assessment showed that the four strains had the usual antibiotic susceptibility profile and did not produce hemolysins. Considering that H87 exhibited a better performance as a probiotic, we investigated the antibacterial substance produced by H87, and identified a bacteriocin with 6.5 kDa. Based on strain characteristics and beneficial properties, we believe that H87 is promising candidate for human trials to confirm its ability to prevent/treat vaginal dysbiosis and maintain a healthy vaginal ecosystem.
... 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 . ...
Article
Full-text available
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.
... 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. ...
Article
Full-text available
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.
... 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. ...
Article
Full-text available
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.
... Although there may be confounders to consider, several lines of evidence suggest L. crispatus can have beneficial effects and that L. iners could be harmful or less protective than L. crispatus (107,108). First, recent clinical trials that administered L. crispatus vaginally after antibiotic treatment for BV or recurrent UTI showed improvement in the recurrence rates of these conditions (109,110). As well, some in vitro studies showed L. iners cultures made less lactic acid compared with L. crispatus cultures, potentially creating a less microbicidal milieu. ...
Article
Full-text available
Bacterial vaginosis (BV) is a polymicrobial condition of the vaginal microbiota associated with a variety of sexually transmitted infections, infections of maternal and fetal tissues during pregnancy, and even some infections outside of the reproductive tract, including the urinary tract and mouth. BV has also been associated with conditions in which the body generates prominent inflammatory reactions to microbes, including infections of the cervix and other upper genital tract tissues. For reasons still not understood, BV is a highly recurrent and often difficult-to-treat condition, complicating attempts to prevent these associated infections. An additional layer of complexity arises from the increasing awareness that the presence of BV-associated bacteria in the vagina is not always symptomatic or associated with adverse outcomes. In this concise Review, we summarize and synthesize three groups of factors grounded in the literature that may be fueling the associations between BV and infection: (a) aspects of society and culture; (b) pathogens, virulence factors, and processes of microbial antagonism and synergy; and (c) host factors, such as genetics and immunity. Our goal is to understand what contexts and combinations of microbial, host, and social factors conspire to make BV virulent in some individuals but not others. Disrupting these patterns more systematically may achieve healthier outcomes.
... The use of probiotics, which supplement vaginal Lactobacillusinstead of targeting pathogenic bacteria, has emerged as a promising therapeutic approach for infectious diseases. Researches have indicated that probiotics can effectively reduce the recurrence rate of BV 25,47,[56][57][58][59] . In the present study, probiotics were evaluated as a standalone treatment for aBV for the first time, and the results demonstrated that probiotics significantly decreased the cumulative recurrence rate of aBV. ...
Article
Full-text available
Asymptomatic Bacterial Vaginosis(aBV)increases the risk of acquiring multiple sexually transmitted diseases, HPV, gynecologic complications and adverse reproductive outcomes, and is speculated to affect 10 ~ 35% of women. Without intervention, a significant proportion of aBV would progress. Metronidazole is the most widely used treatment for aBV, yet the main challenge has always been the high rate of recurrence. Probiotics may increase the cure rate and reduce the recurrence rate of symptomatic bacterial vaginosis (sBV), while no study has compared the efficacy of probiotics and metronidazole on treating aBV. This study aims to fill the gap in understanding the difference in efficacy of probiotics and metronidazole in treating aBV by a multicenter, randomized, controlled trial. Participants received either a 10-day intravaginal probiotic capsules or a 7-day oral metronidazole. Follow-up were performed at the end of the 1st, 2nd, and 4th week after completing therapy. Women cured by either method were followed up with three additional visits. The primary outcome was the difference of cure rates between the two groups. The secondary outcome was to evaluate the recurrence rates among patients who were successfully cured using either method. 358 participants received probiotics and another 358 participants received metronidazole. The cumulative cure rates at the end of the 1st, 2nd, and 4th week were higher in probiotics group compared to metronidazole group (OR 1.063, P = 0.715; OR 1.324, P = 0.083; OR 1.338, P = 0.071), while the differences were not statistically significant. Women cured (144 in probiotics and 123 in metronidazole) were followed up. The difference of cumulative recurrence rates between the two groups were statistically significant at the end of the 2nd, 3rd, and 4th month (OR 0.212, P = 0.000; OR 0.160, P = 0.000; OR 0.119, P = 0.000). Adverse events were similar in the two groups (8.3%, 9.6% OR 0.858; P = 0.584). No life-threatening or severe adverse events were reported. Probiotics emerge as a superior therapeutic option for aBV due to their comparable cure rates, lower recurrence rates, and minimal side effects. Chinese Clinical Trial Registry (ChiCTR1800019436, 11/11/2018 ).
... The intravaginal administration of Lyophilized L. Crispatus IP 174178 can reduce BV's recurrence rate and prolong BV's recurrence time. And vaginal tablet consisting of L. fermentum LF15 and L. plantarum LP01 restored the acidity of imaginary pH and the threshold level of Nugent score to below 7 [43,44]. Healthy vaginal flora is characterized by the balance of lactobacillus, and lactic acid produced by lactobacillus fermentation can inhibit bacteria related to bacterial vaginosis [45]. ...
Article
Full-text available
Background No consensus has yet been reached concerning whether there were significant differences in the vaginal microbiota according to maternal gestational diabetes mellitus (GDM) status. This study aimed to compare the vaginal microbiota of women with GDM and normal blood glucose before and after delivery and to prospectively evaluate the influence of GDM on the dynamic changes of vaginal microbiota from antepartum to postpartum. Methods This study included 20 GDM patients and 31 average pregnant women who gave birth at the Shenzhen Baoan Women’s and Children’s Hospital. Vaginal secretions samples were collected one week before delivery (D0), on the first day of delivery (D1), and 42 days after delivery (D42). Vaginal microbiota was detected using 16S rRNA gene sequencing. Results There was no significant difference in alpha and beta diversity between the GDM and non-GDM groups at each time point (all p > 0.05). However, the overall change patterns in Shannon and Pielou’s evenness index from D0 to D1 to D42 significantly differed between the GDM and non-GDM groups (p = 0.046 and p = 0.032, respectively). The abundance of Lactobacillus decreased obviously after delivery, especially in the GDM group, showing a more severe imbalance of the vaginal microbiota. Conclusions We found that GDM affected the succession of vaginal microbiota in the perinatal period. Our findings provided additional evidence for regulating the vaginal microbiota during pregnancy and postpartum to reduce adverse pregnancy outcomes and achieve long-term vaginal health outcomes.
... Currently, there are many limited treatment options in patients with persistent or recurrent BV despite multiple attempts at antibiotic treatment [97]. In addition, probiotic treatment of symptomatic patients with oral and/or vaginal administration of bacterial strains of Lactobacillus has yielded conflicting results [98], suggesting that the microbiome as a whole, rather than a single bacterial species, may be effective for severe BV. ...
Article
Full-text available
Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients’ intestines to restore gut–immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome—and especially Clostridium difficile infection (currently the only used as clinical treatment)—recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases.
... Indeed, in healthy cervicovaginal microbiota, L. crispatus species prevails, producing D-and L-lactic acid, hydrogen peroxide and bacteriocins, which prevent the overgrowth of possible pathogens, hence preventing upper genital tract infections in the host (Sanozky-Dawes & Barrangou, 2022;Stapleton et al., 2011). For such reason, probiotic supplements based on L. crispatus are widely used as vehicles of health-promoting strains in the vaginal environment (Bohbot et al., 2018;Cohen et al., 2020;Mändar et al., 2023). ...
Article
Full-text available
The lower female reproductive tract is notoriously dominated by Lactobacillus species, among which Lactobacillus crispatus emerges for its protective and health‐promoting activities. Although previous comparative genome analyses highlighted genetic and phenotypic diversity within the L. crispatus species, most studies have focused on the presence/absence of accessory genes. Here, we investigated the variation at the single nucleotide level within protein‐encoding genes shared across a human‐derived L. crispatus strain selection, which includes 200 currently available human‐derived L. crispatus genomes as well as 41 chromosome sequences of such taxon that have been decoded in the framework of this study. Such data clearly pointed out the presence of intra‐species micro‐diversities that could have evolutionary significance contributing to phenotypical diversification by affecting protein domains. Specifically, two single nucleotide variations in the type II pullulanase gene sequence led to specific amino acid substitutions, possibly explaining the substantial differences in the growth performances and competition abilities observed in a multi‐strain bioreactor culture simulating the vaginal environment. Accordingly, L. crispatus strains display different growth performances, suggesting that the colonisation and stable persistence in the female reproductive tract between the members of this taxon is highly variable.
... In a multicentric, randomized, placebo-controlled clinical trial, locally administered estradiol-combined H 2 O 2 -producing L. acidophilus achieved significantly higher cure rate in non-menopausal women with BV [112]. Further trials showed varying results [113,114]. ...
Article
Full-text available
Female reproductive health is strongly associated with healthy vaginal microbiota, which is thought to be ensured by the dominance of certain Lactobacillus species. Lactobacilli control the vaginal microenvironment through several factors and mechanisms. One of them is their ability to produce hydrogen peroxide (H2O2). The role of Lactobacillus-derived H2O2 in the vaginal microbial community has been intensively investigated in several studies with many designs. However, results and data are controversial and challenging to interpret in vivo. Defining the underlying mechanisms responsible for a physiological vaginal ecosystem is crucial since it could directly affect probiotic treatment attempts. This review aims to summarize current knowledge on the topic, focusing on probiotic treatment possibilities.
... When compared to the placebo, MED-01 dramatically decreased the Nugent score [214]. Similarly, when lyophilized L. crispatus IP174178 was compared to a placebo group (16/39 patients), it showed an increased time to recurrence (8/39 patients) [215]. Additionally, inVag, which is delivered vaginally, is a safe and effective method of restoring and/or rebalancing the vaginal microbiota, which is characterized by a prevalence of Lactobacilli (L. ...
Article
Bacterial vaginosis (BV) is a polymicrobial vaginal dysbiosis alongside lactobacillus depletion that primarily affects women of reproductive age. The fishy odor vaginal discharge is the major cause of anaerobic pathogenic bacteria colonization. Symptomatic women face specific catastrophic physiological and immunopathological consequences in addition to an elevated risk of sexually transmitted infections. Further, rash antibiotic therapy has witnessed antimicrobial-resistance amplifying vaginal infections. The emergence of biofilm-associated antimicrobial-resistance has made the issue worsened. This article has gone on to explore novel regimens, advanced diagnosis, and various cutting-edge strategies that are found to be effective in addressing these problems and restoring vaginal health.
... The exclusion criteria for the protocol were as follows: (1) undergoing treatment for severe cardiovascular system, immune system, respiratory system, gastrointestinal tract/liver and biliary system, kidney and urinary system, nervous system, musculoskeletal system, psychiatric, infectious disease, and malignant tumor, (2) vaginal or urinary tract infection, bleeding, or abnormality, (3) pregnant or planning pregnancy, (4) breast feeding, (5) using antibiotics, antibacterial agents, steroids, and immunosuppressants, (6) regularly using health functional foods, probiotics, and lactobacillus products, (7) experience of acupuncture treatment for women's cleanser, vaginal cleanser, sedentary treatment, and vaginal health (within one week of screening visit), (8) uncontrolled hypertension (above 160 mmHg of systolic blood pressure or 100 mmHg of diastolic blood pressure), (9) unregulated diabetics (HbA1C > 6.5%), (10) abnormal creatinine, aspartate aminotransferase or alanine aminotransferase, thyroid stimulating hormone levels, (11) allergic to ingredients of this human-applied test food supplements, and (12) participated in another intervention clinical trial. ...
Article
Full-text available
Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4–6 took MED-01 (5.0 × 109 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that Lactobacillus plantarum was significantly increased in the vagina, whereas harmful bacteria such as Mobiluncus spp., Gardnerella vaginalis, and Atopobium vaginae were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota.
... Recurrence rates ranged from 20.5-30%, while the average time to relapse was 3.75 ± 0.16 months. [20,21] Another type of probiotic, namely Lactobacillus plantarum, is also known to reduce the risk of BV recurrence. However, statistically, this result is not significant. ...
... Furthermore, this includes 1006 and 528 samples of probiotics and probiotics or control, respectively, as shown in Fig. 1. Table 2 shows the characteristics of the included studies (Anukam, Osazuwa, Ahonkhai, et al., 2006;Anukam, Osazuwa, Osemene, et al., 2006;Bohbot et al., 2018;Cohen et al., 2020;Eriksson et al., 2005;Happel et al., 2020;Hemmerling et al., 2010;Hummelen et al., 2010;Larsson et al., 2011;Laue et al., 2018;Marcotte et al., 2019;Martinez et al., 2009;Mastromarino et al., 2009;Russo et al., 2019;Sgibnev & Kremleva, 2020;Vujic et al., 2013). The evidence base determination level was 1b for 16 RCTs, and the studies attained a significant level of quality, with Jadad scores in the range of 3e5. ...
Article
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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.
... 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. ...
Article
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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].
... Selain rute oral, probiotik intravaginal juga menurunkan persentase rekurensi BV secara signifikan. Bohbot et al (2018) menggunakan L. crispatus IP 174178 yang diberikan sekali sehari selama 14 hari dimulai pada hari pertama siklus menstruasi dan diberikan selama 4 siklus menstruasi. Sebanyak 79.5% pasien dari kelompok probiotik tidak mengalami rekurensi hingga akhir studi (hari ke-0 s.d hari ke-112), sedangkan pada kelompok plasebo sebanyak 59% (p=0.0497). ...
Article
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Vaginosis bakterial (BV) merupakan penyebab keputihan tersering pada wanita usia reproduktif. Pada BV, dominasi Lactobacillus pada mikrobiota vagina mengalami pergeseran dan digantikan oleh bakteri anaerob fakultatif ataupun obligat. Walaupun efikasi terapi lini pertama BV masih cukup tinggi, tetapi rekurensi BV masih sering terjadi. Pada kajian literatur ini akan dijabarkan hasil uji klinis probiotik sebagai terapi alternatif untuk menurunkan angka rekurensi BV. Pencarian literatur dilakukan dengan menggunakan database PubMed dan Cochrane dengan kata kunci berupa probiotik, lactobacillus, recurrent, dan bacterial vaginosis. Setelah itu, dilakukan telaah pada 9 studi yang memenuhi kriteria inklusi. Berdasarkan hasil dari tinjauan literatur, penggunaan strain probiotik, dosis, dan durasi probiotik yang berbeda dapat memberi hasil yang bervariatif. Pada beberapa uji klinis, probiotik menunjukkan potensi dalam menurunkan rekurensi BV dibandingkan dengan plasebo. Namun, masih diperlukan penelitian lebih lanjut dengan skala lebih besar untuk menentukan durasi dan dosis yang tepat dalam pemberian probiotik.
... 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]. ...
Article
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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.
... 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]. ...
Article
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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.
... The continuation of this trial is currently underway to further assess adverse events in a larger sample size (34). A randomized trial offering women Lactobacillus crispatus IP 174178 also showed no difference in adverse events between the intervention and placebo groups whilst displaying reduced BV recurrence and longer time to recurrence (35). More speci cally, studies exploring the safety and e cacy of LACTIN-V in non-pregnant women have also displayed encouraging safety data. ...
Preprint
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Background The vaginal microbiota is a determinant for the risk of preterm birth (PTB). Dominance of the vaginal niche by Lactobacillus crispatus associates with term delivery. Vaginal administration of Lactobacillus crispatus as a live biotherapeutic in non-pregnant women leads to colonisation and reduced recurrence of bacterial vaginosis and urinary tract infections. This is a first in-pregnancy observational clinical study of live vaginal biotherapeutics (Lactobacillus crispatus CTV-05 (LACTIN-V, Osel)) in a cohort of pregnant women at high-risk of PTB. The primary aim was to explore safety, tolerability and acceptability of LACTIN-V in pregnancy. Methods Pregnant women at high-risk of PTB were offered a course of LACTIN-V at 14 weeks gestation for 5 consecutive days followed by weekly administration for 6 weeks. Participants were followed up at 15, 18-, 20-, 28- and 36-weeks’ gestation and at delivery for assessment of adverse events, compliance, and tolerance. After study completion, women completed a questionnaire to gauge experience and acceptability. Assessment of adverse events was performed in those women completing LACTIN-V therapy and those who commenced LACTIN-V but later withdrew from the study. Results A total of 73 women were recruited, of whom 8 withdrew, leaving a final cohort size of 61. Overall patient reported compliance to the full course was high (56/60, 93%). Solicited adverse events were reported in 13 women (19%) including changes in vaginal discharge, odour, colour or consistency of urine, itching and vaginal bleeding. One unsolicited adverse event was reported as haematuria at 38 weeks gestation, but was not judged to be related to LACTIN-V and no serious adverse events occurred. One mild adverse event led to withdrawal from the study. A total of 31 women completed an experience and acceptability questionnaire. Women found LACTIN-V easy and comfortable to use and the majority (30/31, 97%) stated they would use LACTIN-V in future pregnancies. Eight women (8/31, 26%) reported that the schedule of use was difficult to remember. The rate of early PTB <34 weeks in this cohort was 3.3% compared to 7% in a historical cohort of 2190 women at similar background PTB risk. Conclusions With satisfactory uptake and good compliance, we demonstrate that LACTIN-V is safe and well accepted in pregnancy, with high tolerability. Further studies are needed to assess rates of Lactobacillus crispatus CTV-05 colonisation and clinical efficacy. Trial Registration The trial is registered at www.clinicaltrials.gov (NCT03992534). Date of registration was June 20, 2019
... Several vaginal probiotics containing Lactobacillus spp. have been designed and tested, and have largely yielded mixed results [213][214][215][216][217][218][219][220] . There are a number of reasons why the efficacies of these probiotics fell short of expectations. ...
Article
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.
... 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). ...
Article
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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. ...
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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 microbiota 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 microbiota 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.
Article
Soʻnggi yillarda inson mikrobiomiga tobora koʻproq eʼtibor berilmoqda. Sekvensiyaga asoslangan texnologiyaning yaratilishi avval muhitlarga ekish orqali aniqlash qiyin boʻlgan koʻp sonli bakteriyalarni aniqlash imkonini berdi. Mikrobom diagnostikasi fanning asosiy yoʻnalishi sifatida paydo boʻldi, shu bilan birga reproduktiv tibbiyot ham rivojlandi. Ayniqsa, implantatsiya yetishmovchiligi sabablarni tadqiq qilish va davolash imkoniyatlari bilan bogʻliq tadqiqotlar koʻpaydi. Shunday qilib, vaginal mikrobiom bepushtlikka taʼsir qiluvchi omil sifatida muhokama qilinadi va davolash imkoniyatlari uchun istiqbolli yoʻl hisoblanadi. Ushbu sharh qin mikrobiomining reproduktiv natijalarga taʼsirini koʻrsatuvchi zamonaviy tadqiqotlar natijalarini tahlil qiladi. Laktobakteriyalar ustun boʻlmagan mikrobiom disbioz bilan hatto bacterial vaginoz bilan bogʻliq ekanligi koʻrsatilgan, Ushbu nomutanosiblik implantatsion yetishmovchilik, odatlangan homila tushishi, rivojlanmagan homiladorlikka olib kelishi mumkin. Shu sababli, mikrobiomni tekshirish hamda antibiotiklar va/yoki probiotiklar bilan birgalikda davolash reproduktiv natijalarini yaxshilash usuli boʻlishi mumkin.
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Bacterial vaginosis (BV) is a common condition characterized by a shift in vaginal microbiome composition that is linked to negative reproductive outcomes and increased susceptibility to sexually transmitted infections. Despite the commonality of BV, standard-of-care antibiotics provide limited control of recurrent BV episodes and development of new biotherapies is limited by the lack of controlled models needed to evaluate new dosing and treatment regimens. Here, we develop an in silico framework to evaluate selection criteria for potential probiotic strains, test adjunctive therapy with antibiotics, and alternative dosing strategies. This computational framework highlighted the importance of resident microbial species on the efficacy of hypothetical probiotic strains, identifying specific interaction parameters between resident non-optimal anaerobic bacteria (nAB) and Lactobacillus spp. with candidate probiotic strains as a necessary selection criterion. Model predictions were able to replicate results from a recent phase 2b clinical trial for the live biotherapeutic product, Lactin-V, demonstrating the relevance of the in silico platform. Results from the computational model support that the probiotic strain in Lactin-V requires adjunctive antibiotic therapy to be effective, and that increasing the dosing frequency of the probiotic could have a moderate impact on BV recurrence at 12 and 24 weeks. Altogether, this framework could provide evidence for the rational selection of probiotic strains and help optimize dosing frequency or adjunctive therapies.
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Objective Bacterial vaginosis is a disease caused by vaginal microecology disorder, which seriously affects female health. At present, there are many drugs to treat BV, and this study aims to compare the efficacy and safety of multiple drugs for BV through a network meta-analysis (NMA). Methods All studies were sourced from PubMed and Embase databases from the establishment date to April 13, 2023. We evaluated the clinical cure success rate and adverse effects (abnormal increase in vaginal discharge, external genital irritation, and vulvar itching) and performed subgroup analyses of the clinical cure success rate for different modes of administration. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. Results We included 42 studies that met the criteria, involving a total of 8382 patients. Network meta-analysis results showed that metronidazole and secnidazole had a higher rate of adverse reactions than placebo (RR 7.06; 95%-CI 2.61-19.10, RR 4.03; 95%-CI 1.63-9.98), the adverse reaction rate of probiotics group was lower than that of metronidazole group (RR 0.44; 95%-CI 0.21-0.93). The clinical cure rate of oral ornidazole was better than clindamycin (RR 16.08; 95%-CI 1.72-150.47), Secnidazole (RR 8.17; 95%-CI 1.66-40.25) and probiotics. Direct meta-analysis results showed that ornidazole had a better clinical cure rate than Secnidazole (RR 1.22; 95%-CI 1.10-1.34), oral ornidazole had a better clinical cure rate than Secnidazole (RR 1.23; 95%-CI 1.11-1.36). The clinical cure rate of vaginal application of sucrose was better than metronidazole (RR 1.12; 95%-CI 1.03-1.21) and metronidazole had a lower clinical cure rate than probiotics (RR 0.68; 95%-CI 0.52-0.88). Conclusions The results of this systematic review and network meta-analysis suggest that ornidazole may be an effective alternative for the treatment of BV, and that sucrose and probiotics are potential BV treatments that need to be validated by more high-quality clinical studies in the future.
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Chapter
Trillions of symbiotic microorganisms have evolved with and continue to live on and within human beings, serving an important role in regulating human health and disease. Their omnipresence has a great influence on almost all the physiological functions of the body, and female reproductive system is no exception. As per the Human Microbiome Project, the vaginal microbiota alone makes up about 9% of the total human microbiota. Any internal or external change in this resident microbial population might lead to dysbiosis, further causing disease pathologies. This undesirable shift in microbiota is also strongly associated with stress and lifestyle imbalance, which are directly linked to poor dietary habits and a sedentary routine. Such unfavourable outcomes of vast urbanisation and industrialisation have increased the incidence of major health issues. One such medical condition is infertility, which is currently perceived as a worldwide health problem. Pathophysiological conditions concerning the reproductive system like endometriosis, dysregulated ovarian functions, cervical factors, uterine complications and vaginal infections also affect female fertility to a great extent. Given that these conditions are usually associated with microbial dysbiosis, modulating the microbial population to reinstate eubiosis can certainly alleviate disease symptoms, thereby helping with disease management strategies. Gut microbiota also actively interacts with sex hormones (a concept called microgenderome) to regulate the circulating level of the latter and thus affect reproductive health in various ways. Therefore, many microorganisms are now being examined for their potential and promising use in developing various treatment approaches, including probiotics, synbiotics, faecal microbiota transfer (FMT) and vaginal microbiota transfer (VMT). The rationale behind all these options lies in rehabilitating the progenitive niche with a healthy microbial population in order to maintain and regulate the female reproductive system homeostasis.
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Bacterial vaginosis (BV) is a recurrent condition that affects millions of women worldwide. The use of probiotics is a promising alternative or an adjunct to traditional antibiotics for BV prevention and treatment. However, current administration regimens often require daily administration, thus contributing to low user adherence and recurrence. Here, electrospun fibers were designed to separately incorporate and sustain two lactic acid producing model organisms, Lactobacillus crispatus (L. crispatus) and Lactobacillus acidophilus (L. acidophilus). Fibers were made of polyethylene oxide and polylactic-co-glycolic acid in two different architectures, one with distinct layers and the other with co-spun components. Degradation of mesh and layered fibers was evaluated via mass loss and scanning electron microscopy. The results show that after 48 h and 6 days, cultures of mesh and layered fibers yielded as much as 108 and 109 CFU probiotic/mg fiber in total, respectively, with corresponding daily recovery on the order of 108 CFU/(mg·day). In addition, cultures of the fibers yielded lactic acid and caused a significant reduction in pH, indicating a high level of metabolic activity. The formulations did not affect vaginal keratinocyte viability or cell membrane integrity in vitro. Finally, mesh and layered probiotic fiber dosage forms demonstrated inhibition of Gardnerella, one of the most prevalent and abundant bacteria associated with BV, respectively resulting in 8- and 6.5-log decreases in Gardnerella viability in vitro after 24 h. This study provides initial proof of concept that mesh and layered electrospun fiber architectures developed as dissolving films may offer a viable alternative to daily probiotic administration.
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Recent work by Muraoka and colleagues reports that the Gram-negative anaerobic bacterium Fusobacterium nucleatum is detected in the uterus of 64% of women with endometriosis. Fusobacterium infection causes macrophage infiltration, transforming growth factor-β production, and transgelin upregulation in human and mouse endometria as well as endometriotic lesion development in a mouse model of endometriosis.
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Bacterial vaginosis (BV) is a common cause of vaginitis worldwide and is associated with serious reproductive health outcomes, including increased risk of preterm birth, sexually transmitted infections, and pelvic inflammatory disease. The current and only FDA-approved treatment regimens for BV are antibiotics, such as metronidazole and clindamycin. Antibiotics provide a short-term cure for bacterial vaginosis; however, fail to provide a consistent long-term cure for many women. Fifty to eighty percent of women experience a BV recurrence within a year of completing antibiotic treatment. This may be because after antibiotic treatment, beneficial strains of Lactobacillus , such as L. crispatus, do not recolonize the vagina. In the absence of an effective long-term cure, patients, providers, and researchers are exploring different approaches to treatment and prevention, resulting in a rapid evolution of perspectives on BV pathogenesis and approaches to management. Current areas of investigation for BV management include probiotics, vaginal microbiome transplantation, pH modulation, and biofilm disruption. Behavioral modifications that may help include smoking cessation, condom use and hormonal contraception. Additional strategies considered by many people include dietary modification, non-medical vaginally applied products, choice of lubricant, and treatments from medical practices outside of allopathic medicine. This review aims to provide a comprehensive and up to date outline of the landscape of ongoing and potential treatment and prevention strategies for BV.
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Title "Soil Quality and Ecosystem Services: Towards a New Perspective of Soil Use and Management" Edited by Ugo De Corato Description A natural balance of all soil components is needed between the physical, chemical, and biological properties that characterize a healthy soil ecosystem. The focus of this Special Issue is to give a general description of ecosystem services and representative indicators for a selection of specific soil types in relation to land use. The scope of the Special Issue is aimed at developing a rational soil use and management for a systematic approach for identifying the highest-risk scenarios in land use in view of environmental stressors, based on vulnerability assessment of indicators for ecosystem services. The purpose of this Special Issue is to cover all the aforementioned aspects and mechanisms governing the natural and anthropogenic processes which affect soil systems. It will document the sustainable use and management of soil resources and cover specific key points, such as the complex ecological roles of soil organisms and their multiple interactions in relation to sustainability and productivity, nutrient cycling, soil structure formation and modification affected by soil biota and other soil processes, the maintenance of soil functions, the impact of human activities on soil ecosystems, and bio(techno)logical control of soil-inhabiting plant pests, plant diseases, and weeds. In addition, specific papers focused on biocontrol of soil-borne plant pathogens by use of organic amendments by agricultural waste recycling (e.g., compost, biochar, digestate, sewage sludge) are particularly welcomed regarding a specific topic to satisfy the soil quality and ecosystem service requirements. This Special Issue will supplement the existing literature through interdisciplinary studies, e.g., linking soil with climate change, biodiversity, global health, and the sustainable development goals, with strong novelty, wide implications, and unexpected outcomes. Keywords: Applied soil ecology Ecosystem service Land use Soil-borne plant pathogen Soil biota Soil indicator Soil quality
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Bacterial vaginosis (BV) is characterized by low levels of lactobacilli and overgrowth of potential pathogens in the female genital tract. Current antibiotic treatments often fail to treat BV in a sustained manner, and > 50% of women experience recurrence within 6 months post-treatment. Recently, lactobacilli have shown promise for acting as probiotics by offering health benefits in BV. However, as with other active agents, probiotics often require intensive administration schedules incurring difficult user adherence. Three-dimensional (3D)-bioprinting enables fabrication of well-defined architectures with tunable release of active agents, including live mammalian cells, offering the potential for long-acting probiotic delivery. One promising bioink, gelatin alginate has been previously shown to provide structural stability, host compatibility, viable probiotic incorporation, and cellular nutrient diffusion. This study formulates and characterizes 3D-bioprinted Lactobacillus crispatus-containing gelatin alginate scaffolds for gynecologic applications. Different weight to volume (w/v) ratios of gelatin alginate were bioprinted to determine formulations with highest printing resolution, and different crosslinking reagents were evaluated for effect on scaffold integrity via mass loss and swelling measurements. Post-print viability, sustained-release, and vaginal keratinocyte cytotoxicity assays were conducted. A 10:2 (w/v) gelatin alginate formulation was selected based on line continuity and resolution, while degradation and swelling experiments demonstrated greatest structural stability with dual genipin and calcium crosslinking, showing minimal mass loss and swelling over 28 days. 3D-bioprinted L. crispatus-containing scaffolds demonstrated sustained release and proliferation of live bacteria over 28 days, without impacting viability of vaginal epithelial cells. This study provides in vitro evidence for 3D-bioprinted scaffolds as a novel strategy to sustain probiotic delivery with the ultimate goal of restoring vaginal lactobacilli following microbiological disturbances.
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The vaginal microbiota is a determinant for the risk of preterm birth (PTB). Dominance of the vaginal niche by Lactobacillus crispatus associates with term delivery. This is the first observational clinical study of live vaginal biotherapeutics (Lactobacillus crispatus CTV-05 (LACTIN-V)) in pregnant women at high-risk of PTB. The primary aim was to explore safety, tolerability and acceptability of LACTIN-V in pregnancy. Women were offered a course of LACTIN-V at 14 weeks gestation for five consecutive days followed by weekly administration for six weeks. Participants were followed up at 15, 18-, 20-, 28- and 36-weeks' gestation and at delivery for assessment of adverse events, compliance and tolerability. Participants completed a questionnaire to gauge experience and acceptability. In total, 73 women were recruited, of whom eight withdrew, leaving a final cohort size of 61. Self-reported compliance to the course was high (56/60, 93%). Solicited adverse events were reported in 13 women (19%) including changes in vaginal discharge, odour, colour or consistency of urine, itching and vaginal bleeding. One unsolicited adverse event was reported as haematuria at 38 weeks gestation, but was judged to be unrelated to LACTIN-V. No serious adverse events occurred. One mild adverse event led to study withdrawal. Thirty-one women completed an experience and acceptability questionnaire. Women found LACTIN-V easy and comfortable to use and the majority (30/31, 97%) would use LACTIN-V in future pregnancies. Eight women (8/31, 26%) found the schedule of use difficult to remember. The rate of PTB <34 weeks in this cohort was 3.3% compared to 7% in a historical cohort of 2,190 women at similar background PTB risk. With satisfactory uptake and good compliance, we demonstrate that LACTIN-V is safe and accepted in pregnancy, with high tolerability. Further studies are needed to assess colonisation of Lactobacillus crispatus CTV-05 and clinical efficacy.
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738 www.medicinainterna.org.mx rEvisión narrativa Med Int Méx. 2021; 37 (5): 738-758. Experiencias clínicas con Lactobacillus (2016-2019) Resumen 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.
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Lactobacillus iners is often associated with increased risk of adverse gynecological and obstetric outcomes, such as vaginal dysbiosis and bacterial vaginosis (BV). Lactobacillus strains from the vagina of healthy women were screened for inhibitory activity against L. iners. Four active strains were identified, whereby L. gasseri H87 exhibited the highest inhibitory activity against L. iners , followed by L. rhamnosus H23. All four strains inhibited the growth of potential pathogens of the gastrointestinal, urogenital and reproductive tract, and were capable of co-aggregating with the cells of the tested pathogens to varying degrees. H23 and H78 exhibited survival rates above 80% under in vitro conditions simulating the vaginal, gastric and intestinal environment. The four strains showed good auto-aggregation of more than 30%. H23 and H87 also exhibited good co-aggregation of more than 30% with Listeria monocytogenes and Escherichia coli. Safety assessment showed that the four strains had the usual antibiotic susceptibility profile and did not produce hemolysins. Considering that H87 exhibited a better performance as a probiotic, we investigated the antibacterial substance produced by H87, and identified a bacteriocin with a molecular weight of 6.5 kDa. Based on strain characteristics and beneficial properties, we confirmed its ability to prevent/treat vaginal dysbiosis and maintain a healthy vaginal ecosystem. Therefore, we believe that H87 is a promising candidate for human trials.
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Background: The genomic approach has deeply changed the microbiology perspective, mainly concerning the microbioma identification. In this regard, some microbes colonize the healthy vagina. Vaginitis is a common gynecological ailment and includes bacterial vaginosis (BV), usually caused by local dysbiosis, such as a microbiota imbalance. Lactobacilli are the most prevalent bacteria colonizing the healthy vagina, so guaranteeing local eubiosis. In particular, vaginal colonization by L. crispatus is associated with low susceptibility to BV. Therefore, probiotics, such as life bacteria providing health advantages, are a current strategy in the prevention or treatment of vaginitis, including BV. However, there is a low level of evidence that probiotics after ingestion could really colonize the vagina. In particular, no study evidenced that L crispatus after ingestion can colonize vagina. Therefore, the current study explored the capacity of Biovaginil® (dietary supplement containing Lactobacillus crispatus NTCVAG04 and vitamin A) to colonize the gut and vagina in women with a history of vaginitis/vaginosis. Results: Twenty fertile females (mean age 34.0 years) were enrolled in the study. Rectal and vaginal swabs were collected at baseline and after the first and second cycle of Biovaginil®. Each cycle lasted 14 days within two consecutive menstrual periods. Seven women were excluded from the analysis because the samples were technically not evaluable. One woman dropped out because of mild adverse event. At the end of the study, 9 women (75%) had positive rectal swab for L. crispatus NTCVAG04, and 8 of them also had positive vaginal swab. Conclusions: The current study provided the first evidence that L. crispatus NTCVAG04, administered by two Biovaginil® courses, colonized both the gut and vagina. Moreover, the L. crispatus NTCVAG04 strain could be considered the archetype of a new class of oral probiotics that actively colonize the vagina, and that could be called "colpobiotics.
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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.
Chapter
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.
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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.
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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.
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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.
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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.
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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.
Article
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.