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Ecological dynamics of the vaginal microbiome in relation to health and disease
Abstract
The bacterial composition of the vaginal microbiome is thought to be related to health and disease states of women. This microbiome is particularly dynamic, with compositional changes related to pregnancy, menstruation, and disease states such as bacterial vaginosis. In order to understand these dynamics and their impact on health and disease, ecological theories have been introduced to study the complex interactions between the many taxa in the vaginal bacterial ecosystem. The goal of this review is to introduce the ecological principles that are used in the study of the vaginal microbiome and its dynamics, and to review the application of ecology to vaginal microbial communities with respect to health and disease. Although applications of vaginal microbiome analysis and modulation have not yet been introduced into the routine clinical setting, a deeper understanding of its dynamics has the potential to facilitate development of future practices, for example in the context of postmenopausal vaginal symptoms, stratifying risk for obstetric complications, and controlling sexually transmitted infections.
... The female reproductive tract is composed of two distinct microbial environments. [17][18][19][20][21][22][23] Many microbial species inhabit the lower female reproductive tract, including the vagina and cervix. 17 21 In contrast, the upper female reproductive tract, composed of the uterus, fallopian tubes, and ovaries, was historically considered sterile. ...
... Additionally, Lactobacillus prevents the adhesion and growth of pathogenic bacteria through the production of bactericidal compounds 17 19 21 (Table 1). Notably, dysbiosis of the vaginal microbiota with increased representation of anaerobic non-Lactobacillus species, especially in patients with community state type-IV, has been linked with multiple disease states, including the persistence of the human papillomavirus (HPV) and the development of gynecologic cancers [17][18][19][20][21][22] (Table 1). ...
... In contrast, high-quality evidence characterizing the distinct microbiota of the upper female reproductive tract of healthy women is limited. [18][19][20][21][22][23][24] More recently, in a cross-sectional study of 10 women after hysterectomy, the relative abundance of bacterial species in the endometrium and myometrium was lower than in the cervicovaginal microbiome but highly varied, with fewer Lactobacillus Figure 1 Factors impacting the composition of gut and female reproductive tract microbiota. ...
The microbiome plays a vital function in maintaining human health and homeostasis. Each microbiota has unique characteristics, including those of the gastrointestinal and female reproductive tract. Dysbiosis, or alterations to the composition of the microbial communities, impacts the microbiota–host relationship and is linked to diseases, including cancer. In addition, studies have demonstrated that the microbiota can contribute to a pro-carcinogenic state through altered host immunologic response, modulation of cell proliferation, signaling, gene expression, and dysregulated metabolism of nutrients and hormones.
In recent years, the microbiota of the gut and female reproductive tracts have been linked to many diseases, including gynecologic cancers. Numerous pre-clinical and clinical studies have demonstrated that specific bacteria or microbial communities may contribute to the development of gynecologic cancers. Further, the microbiota may also impact the toxicity and efficacy of cancer therapies, including chemotherapy, immunotherapy, and radiation therapy in women with gynecologic malignancies. The microbiota is highly dynamic and may be altered through various mechanisms, including diet, exercise, medications, and fecal microbiota transplantation. This review provides an overview of the current literature detailing the relationship between gynecologic cancers and the microbiota of the female reproductive and gastrointestinal tracts, focusing on mechanisms of carcinogenesis and strategies for modulating the microbiota for cancer prevention and treatment. Advancing our understanding of the complex relationship between the microbiota and gynecologic cancer will provide a novel approach for prevention and therapeutic modulation in the future.
... Vaginal biofilms play a role in bacterial vaginosis (BV) pathogenesis, resulting in the recurrence of infection [1]. The structure of the biofilm limits the antibiotic penetration into the matrix as well as the interaction with the bacteria [2][3][4]. ...
... Reoccurrence and antimicrobial resistance were experienced by people diagnosed with bacterial vaginosis due to the increasing rates of treatment failure [1,9]. It is important that drug delivery systems can penetrate the bacteria biofilm and, in the process, restore healthy vaginal flora. ...
... BV has been linked with an increased risk of contracting sexually transmitted infections (STIs), human immunodeficiency virus (HIV), herpes simplex virus, chlamydia, and gonorrhea [5,6]. In 2019, BV was the most prevalent vaginal infection and was estimated to affect from 5% to 70% of people globally [1]. Vaginal biofilms play a major role in treatment failure, as they possess structures that prevent antimicrobial penetration and the further contact with microorganisms, leading to antibi-otics resistance and affecting drug release, which modified drug solubility and reduced drug effectiveness [2][3][4][5][6][7]. ...
Bacterial vaginosis (BV) is an infection of the vagina associated with thriving anaerobes, such as Gardnerella vaginitis and other associated pathogens. These pathogens form a biofilm responsible for the recurrence of infection after antibiotic therapy. The aim of this study was to develop a novel mucoadhesive polyvinyl alcohol and polycaprolactone electrospun nanofibrous scaffolds for vaginal delivery, incorporating metronidazole, a tenside, and Lactobacilli. This approach to drug delivery sought to combine an antibiotic for bacterial clearance, a tenside biofilm disruptor, and a lactic acid producer to restore healthy vaginal flora and prevent the recurrence of bacterial vaginosis. F7 and F8 had the least ductility at 29.25% and 28.39%, respectively, and this could be attributed to the clustering of particles that prevented the mobility of the crazes. F2 had the highest at 93.83% due to the addition of a surfactant that increased the affinity of the components. The scaffolds exhibited mucoadhesion between 31.54 ± 0.83% and 57.86 ± 0.95%, where an increased sodium cocoamphoacetate concentration led to increased mucoadhesion. F6 showed the highest mucoadhesion at 57.86 ± 0.95%, as compared to 42.67 ± 1.22% and 50.89 ± 1.01% for the F8 and F7 scaffolds, respectively. The release of metronidazole via a non-Fickian diffusion-release mechanism indicated both swelling and diffusion. The anomalous transport within the drug-release profile pointed to a drug-discharge mechanism that combined both diffusion and erosion. The viability studies showed a growth of Lactobacilli fermentum in both the polymer blend and the nanofiber formulation that was retained post-storage at 25 °C for 30 days. The developed electrospun scaffolds for the intravaginal delivery of Lactobacilli spp., along with a tenside and metronidazole for the management of bacterial vaginosis, provide a novel tool for the treatment and management of recurrent vaginal infection.
... A fundamental step in the study of the vaginal ecosystem is the identification of microorganisms adhered to vaginal mucosa [74]. Several studies have employed the real-time qPCR technique to sequence the 16S rRNA gene and establish the composition of the microorganisms present in a sample resulting from the vaginal microenvironment [75][76][77][78], especially the dominant vaginal bacteria such as lactobacilli in the studies conducted by Di Bella et al. [79], Chen et al. [80], Hardy et al. [81], and Vitali et al. [82]. ...
... Nevertheless, these researchers pointed out that CST IV is the only group that has a significant diversity of facultative and obligate anaerobes. According to Greenbaum et al. [74], the strong correlation between microorganisms of the Lactobacillus genus and the vaginal bacterial community contributes to the acidification process, which is a barrier that hinders the adhesion and proliferation of pathogens in the vaginal tract. It is noteworthy that beneficial effects promoted by lactobacilli on the vaginal microbiome do not occur only in isolation, but through a multimicrobial interaction [93]. ...
Women’s health is related to several factors that include physical, mental, and reproductive health. Additionally, the vaginal microbiota modulation performs a fundamental role in the regulation of physiological homeostasis and dysbiosis, which provides us a potential overview of the use of different biotic agents and their implications for female health. The objective of this work was propitiated insights and conception about the influence of probiotics, prebiotics, synbiotics, and postbiotics as adjuvants for prevention/treatment on the main infections that can affect women’s health. Therefore, seventy-one studies published in the Web of Science Core Collection database from 1999 to 2024 were evaluated and performed to a bibliometric analysis employing the VOSviewer software for scientific mapping and network analysis. Our results suggest that administration of biotic agents as adjuvants are relevant for the prevention and/or treatment of the main diseases that affect female health, since they contribute to a healthy vaginal microbiota through anti-inflammatory and antimicrobial activities. Most clinical studies have demonstrated the effectiveness of intervention using probiotics to the detriment of other biotic agents in women’s health, being bacterial vaginosis, polycystic ovary syndrome, and vulvovaginal candidiasis, the main diseases evaluated. However, preclinical studies have emphasized that the inhibition of pathogens responsible for the process of vaginal dysbiosis may be due to the formation of biofilm and the synthesis of compounds that could prevent the adhesion of these microorganisms. Future perspectives point to the beneficial modulation of the vaginal microbiota by biotic agents as a promising adjuvant approach to improve women’s health.
... Исследования, проведенные Всемирной организацией здравоохранения, показали, что в 2022 году около 500 тысяч женщин во всем мире имели диагноз «рак шейки матки», из них около 342 тысяч человек погибли от этого заболевания. По данным Ассоциации онкологов Лактобациллы, которые присутствуют во влагалище, способствуют поддержанию этого баланса [9,10]. ...
... Условно-патогенные микроорганизмы, которые обычно не вызывают заболевания, содержатся в транзиторной микрофлоре. Они колонизируют влагалище в ограниченных количествах, поскольку конкурируют с другими бактериями [10]. Дисбаланс между лактобактериями и условно-патогенными микроорганизмами под влиянием внутренних и внешних факторов может привести к нарушению микрофлоры и возникновению инфекции [11]. ...
... However, in the candidiasis model that was formed, it produces an alkaline vaginal pH of more than 8.5 with a range from 8.8−9.3. The vaginal pH in humans tends to be acid due to the normal flora of Lactobacillus which produces lactic acid [23,24], whereas in rats there are no Lactobacillus. Various environmental groups can influence the morphology of C. albicans. ...
... Insemination of sperm in the vagina does not significantly affect changes in pH in the vagina. The natural acidity group in the vagina determined by the microbiome greatly determine the pH in the vagina [23][24][25]. ...
Sexual violence is a global issue affecting individuals regardless of their relationship to the perpetrator or the setting. Microscopic examination of spermatozoa from vaginal swabs is crucial in investigating cases of sexual intercourse to determine the time of the crime. Factors such as vaginal pH and neutrophil count influence the motility and persistence of spermatozoa in the vagina, particularly in conditions like candidiasis, highlighting the need for further research in this area. This study aimed to determine the effect of pH and neutrophil count on the motility and persistence of spermatozoa in the vagina with candidiasis. An experimental study was conducted using white rats (Rattus norvegicus) of the Wistar strain, with four male rats providing spermatozoa samples and 32 female rats receiving treatment. The female rats were divided into two groups: the normal group and the candidiasis model group. In both groups, the female rats were given vaginal insemination of spermatozoa. Variables measured included pH, neutrophil count, motility, and persistence of spermatozoa in the vagina. Data were analyzed using the Mann-Whitney test, followed by the Spearman correlation test. The findings revealed that spermatozoa motility lasted up to three minutes in normal rats, whereas in the candidiasis model, it was reduced to two minutes. Additionally, spermatozoa persistence in the vagina lasted up to six days in the normal group compared to up to three days in the candidiasis model. There were significant differences in pH, neutrophil count, motility, and persistence of spermatozoa in the vagina between the normal group and the candidiasis model (all had p<0.001). There was a correlation between pH and neutrophil count with the motility and persistence of spermatozoa in the rat’s vagina (p<0.001). In conclusion, vaginal pH and neutrophil count influence the motility and persistence of spermatozoa in the vagina of candidiasis rat models.
... The vaginal microbiota is dominated by bacteria of the genus Lactobacillus and low bacterial diversity. These bacteria produce lactic acid which makes it unfavorable for the growth of pathogens, and the production of hydrogen peroxide and bacteriocins further enhances this effect (Greenbaum et al. 2018;Taddei et al. 2018). In addition, the vaginal microbiota is distinguished by variability and instability. ...
... In addition, the vaginal microbiota is distinguished by variability and instability. As a result, it is difficult to unequivocally define the composition of normal vaginal microbiota for all women, especially given that even for a single woman the composition can change over time (Greenbaum et al. 2018). The composition of vaginal microbiota fluctuates under the influence of many factors (Kervinen et al. 2019). ...
Genetic, endocrine and immunological disorders, anatomical defects in the reproductive tract, certain chronic diseases, toxic substances, or advanced age of the mother are most cited among the main causes of pregnancy loss at various stages. However, the cause of miscarriage or preterm labor in some cases remains unclear. Determination of the etiology about these clinical conditions may reduce the rate of reproductive failure. Similarly, the etiology of other obstetric disorders, such as preeclampsia or postpartum hemorrhage, has not been fully explained. One of the postulated and still under-researched causes of these disorders may be dysbiosis within the reproductive tract. A disturbed microbial balance is not always associated with the presence of an acute infection with clear clinical symptoms. Dysbiosis in conjunction with other pathophysiological factors may increase the risk of the mentioned clinical conditions. The aim of this paper is to show the information indicating the existence of a correlation between dysbiosis and an increase in the risk of obstetric disorders. Further analysis is also required to clarify the mechanism of the effect of dysbiosis on the disruption of metabolic and biochemical processes within the reproductive system during pregnancy.
... The vaginal microecosystem consists of a complex and dynamic microbiome that coexists in a symbiotic relationship with the host (1) and the diversity of the vaginal microbiome plays a vital role in vaginal health. The vaginal normal flora of women within the reproductive age harbors 10 10 -10 11 bacteria predominantly Lactobacillus species (2,3). Despite the vast number of bacteria in the vaginal ecosystem, fungi contribute to the promotion of vaginal health. ...
... The obtained ITS sequence from the isolate produced an exact match during the MegaBlast search for highly similar sequences from the NCBI non-redundant nucleotide (nr/nt) database. Candida isolates designated 1, 3,5,6,8,9,11,12,13,14,15,17,23,25 and 27 were identified as C. albicans; isolates 24,2,22,4,19 and 20 were C. glabrata (N. glabrata); isolates 16,21 and 26 were C. tropicalis; and isolate 18 was identified as C. parapsilosis. ...
Background: The use of contraceptive devices predisposes women to vulvovaginal candidiasis (VVC) globally. Despite the high incidence of VVC and antifungal resistance to azoles, the genetic diversity and resistance pattern among contraceptive users in Nigeria is poorly investigated. This study therefore sought to characterize and determine the phylogenetic breadth of Candida species as well as their resistance to antifungal agents. Methodology: This study recruited 1,600 women using contraceptive devices who visited selected gynaecology and obstetrics clinics in northcentral Nigeria. Candida species were isolated and characterized using conventional methods and sequencing of the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA). Bayesian phylogenetic analysis was used to characterize the diversity of Candida species and primer-specific PCR was used to detect the presence of resistant genes. Agar well diffusion technique was used for the determination of antifungal susceptibility profiles. Data analysis was done by Kruskal-Wallis Chi-square test on R Console software version 3.2.2, followed by post-hoc Wilcoxon rank sum test with Bonferroni correction for multiple pairwise comparisons of means where there was a significant difference between the antifungal agents. The level of significance was set at p < 0.05. Results: A total of 710 (44.3%) out of the 1,600 women using contraceptive devices had VVC with five species of Candida identified in them. Although Candida albicans was the predominant (43.2%, n=307) species, other non-albicans Candida species include Candida (Nakaseomyces) glabrata (19.0%, n=135), Candida tropicalis (15.8%, n=112), Candida parapsilosis (8.9%, n=63), and Candida akabanensis (13.1%, n=93) which were phenotypically identified as Candida (Nakaseomyces) glabrata. All the Candida species showed varying degrees of susceptibilities to voriconazole, fluconazole and nystatin. However, resistance of C. albicans to fluconazole was 29.0%, C. tropicalis to nystatin (46.0%) and to voriconazole (14.0%), while C. akabanensis was 100.0% resistant to voriconazole and fluconazole. Kruskal-Wallis Chi-square test showed nystatin as the most effective antifungal agent against the Candida species (χ2=786.03, df=2, p<0.001). Also, resistant gene Erg11 was identified in all the Candida species that were phenotypically resistant to the antifungal agents tested. Conclusion: Women using contraceptive devices in northcentral Nigeria harbor phylogenetically diverse Candida species including C. akabanensis, an uncommon cause of VVC. Of these Candida species, C. albicans, C. tropicalis and C. akabanensis were notable for multidrug drug resistance as well as harboring Erg11 resistance gene. Contexte: L'utilisation de dispositifs contraceptifs prédispose les femmes à la candidose vulvo-vaginale (CVV) à l'échelle mondiale. Malgré l'incidence élevée de la CVV et de la résistance antifongique aux azoles, la diversité génétique et les modèles de résistance parmi les utilisatrices de contraceptifs au Nigéria sont peu étudiés. Cette étude a donc cherché à caractériser et déterminer l'étendue phylogénétique des espèces de Candida ainsi que leur résistance aux agents antifongiques. Méthodologie: Cette étude a recruté 1600 femmes utilisant des dispositifs contraceptifs qui ont visité des cliniques de gynécologie et d'obstétrique sélectionnées dans le centre-nord du Nigeria. Les espèces de Candida ont été isolées et caractérisées à l'aide de méthodes conventionnelles et du séquençage de la région de l'espaceur transcrit interne (ITS) de l'ADN ribosomal (ADNr). L'analyse phylogénétique bayésienne a été utilisée pour caractériser la diversité des espèces de Candida et la PCR spécifique aux amorces a été utilisée pour détecter la présence de gènes résistants. La technique de diffusion dans des puits de gélose a été utilisée pour la détermination des profils de sensibilité aux antifongiques. L'analyse des données a été effectuée par le test du chi carré de Kruskal-Wallis sur la version 3.2.2 du logiciel R Console, suivi d'un test de somme de rangs de Wilcoxon post-hoc avec correction de Bonferroni pour de multiples comparaisons par paires de moyennes où il y avait une différence significative entre les agents antifongiques. Le niveau de signification a été fixé à p<0,05. Résultats: Au total, 710 (44,3%) des 1600 femmes utilisant des dispositifs contraceptifs présentaient une VVC contenant cinq espèces de Candida. Bien que Candida albicans soit l'espèce prédominante (43,2%, n=307), d'autres espèces de Candida non albicans comprennent Candida (Nakaseomyces) glabrata (19,0%, n=135), Candida tropicalis (15,8%, n=112), Candida parapsilosis (8,9%, n=63) et Candida akabanensis (13,1%, n=93), phénotypiquement identifiés comme étant Candida (Nakaseomyces) glabrata. Toutes les espèces de Candida présentaient divers degrés de sensibilité au voriconazole, au fluconazole et à la nystatine. Cependant, la résistance de C. albicans au fluconazole était de 29,0%, celle de C. tropicalis à la nystatine (46,0%) et au voriconazole (14,0%), tandis que celle de C. akabanensis était de 100,0% résistante au voriconazole et au fluconazole. Le test du Chi carré de Kruskal-Wallis a montré que la nystatine était l'agent antifongique le plus efficace contre l'espèce Candida (χ2=786,03, df=2, p<0,001). En outre, le gène résistant Erg11 a été identifié chez toutes les espèces de Candida qui étaient phénotypiquement résistantes aux agents antifongiques testés. Conclusion: Les femmes utilisant des dispositifs contraceptifs dans le centre-nord du Nigéria abritent des espèces de Candida phylogénétiquement diverses, notamment C. akabanensis, une cause rare de CVV. Parmi ces espèces de Candida, C. albicans, C. tropicalis et C. akabanensis se distinguaient par leur multirésistance aux médicaments et par l'hébergement du gène de résistance Erg11.
... In menopausal women, Lactobacillus is always decreased and anaerobic taxa, including Bacteroides and Mobiluncus, are increased [29]. The changes are widely attributed to hormonal changes during menses or post-menopause [30]. There is evidence that hormone replacement therapy can restore vaginal Lactobacilli following menopause [3,31], and vaginal estrogen therapy has been associated with increased Lactobacillus in the urine of postmenopausal women [32]. ...
... The current opinion is that estrogen promotes the maturation, proliferation, and accumulation of glycogen in vaginal epithelial cells and that glycogen is to lactic acid by Lactobacillus species, which creates an acidic environment that favors the growth of Lactobacillus [33]. However, as the predominant vaginal bacteria in more than 50% of postmenopausal women are Lactobacilli, [34,35] simple estrogen-based hypotheses do not explain this phenomenon [30]. ...
Background
The association between the vaginal microbiome and polycystic ovary syndrome (PCOS) is reported, but the longitudinal changes in the vaginal microbiome that accompany oral contraceptive therapy have not been described.
Methods
This cohort study included 50 PCOS patients who wanted to make their menstrual periods more regular and accepted only oral contraceptive therapy and lifestyle coaching, then they were successfully followed up for 6 months. Venous blood was collected, and follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (T), anti-Müllerian hormone (AMH), and estradiol (E2) were assayed at baseline and at months 3 and 6. Vaginal swabs were collected at baseline and at months 3 and 6. 16S rRNA genes were sequenced to identify the microbiota structure. Latent class trajectory models were used to explore the trajectory of the changes in Lactobacillus abundance.
Results
At 3 months, all patients reported regular periods, and the improvement lasted until 6 months. The body mass index and waist-to-hip ratio decreased with treatment ( P < 0.01), and the AMH and T levels showed downward trends. We did not find a statistically significant relationship between hormone levels at the previous time point and the vaginal microbiota at subsequent time points ( P > 0.05). The relative abundance of Lactobacillus increased with treatment, and trajectory analysis revealed five classes of Lactobacillus changes. Class 1, stable high level, accounted for 26%; class 2, decrease followed by increase, accounted for 18%; class 3, stable low level, accounted for 10%; class 4, increase, accounted for 20%; class 5, increase followed by decrease, accounted for 26%. Logistic models showed that compared to class 1, a higher baseline T level was associated with a reduced risk of class 2 change (odds ratio (OR) = 0.03, 95% confidence interval (CI):0.01–0.52) and class 4 change (OR = 0.10, 95% CI:0.01–0.93).
Conclusions
The abundance of Lactobacilli increased with PCOS treatment; however, the trajectory was inconsistent for each individual. Evidence of the effects of female hormone levels on the vaginal microbiome is insufficient.
... Vaginal infections are common gynecological conditions that significantly affect the health and quality of life of women of all ages [1]. The vaginal microbiome is uniquely complex and differs considerably from that of other body sites, potentially influencing various health conditions [2]. Disruption of the vaginal microecosystem often leads to vaginal infection, inflammation, or imbalance in normal bacteria [1,3]. ...
Background
Vaginal infections caused by multidrug-resistant pathogens such as Candida albicans and Gardnerella spp. represent a significant health challenge. Current treatments often fail because of resistance and toxicity. This study aimed to synthesize and characterize a novel amphiphilic polypeptide, KF-5, and evaluate its antibacterial and antifungal activities, biocompatibility, and potential mechanisms of action.
Results
The KF-5 peptide was synthesized via solid-phase peptide synthesis and self-assembled into nanostructures with filamentous and hydrogel-like configurations. Characterization by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) confirmed the unique nanostructural properties of KF-5. KF-5 (125, 250, or 500 µg/ml) demonstrated potent antibacterial and antifungal activities, with significant inhibitory effects on drug-resistant Candida albicans and Gardnerella spp. (P < 0.05). In vitro assays revealed that 500 µg/ml KF-5 disrupted microbial cell membranes, increased membrane permeability, and induced lipid oxidation, leading to cell death (P < 0.05). Cytotoxicity tests revealed minimal toxicity in human vaginal epithelial cells, keratinocytes, and macrophages, with over 95% viability at high concentrations. Molecular dynamics simulations indicated that KF-5 interacts with phospholipid bilayers through electrostatic interactions, causing membrane disruption. In vivo studies using a mouse model of vaginal infection revealed that 0.5, 1, and 2 mg/ml KF-5 significantly reduced fungal burden and inflammation, and histological analysis confirmed the restoration of vaginal mucosal integrity (P < 0.01). Compared with conventional antifungal treatments such as miconazole, KF-5 exhibited superior efficacy (P < 0.01).
Conclusions
KF-5 demonstrates significant potential as a safe and effective antimicrobial agent for treating vaginal infections. Its ability to disrupt microbial membranes while maintaining biocompatibility with human cells highlights its potential for clinical application. These findings provide a foundation for further development of KF-5 as a therapeutic option for combating drug-resistant infections.
... An imbalance of the normal genital tract microbiota results in bacterial vaginosis (BV). It is one of the most frequent causes of abnormal vaginal discharge in women of reproduc-tive age, particularly in pregnant women [1]. It results from an imbalance in the vaginal microbiota characterized depletion of hydrogen-peroxide producing lactobacilli and replaced by 82 anaerobic microorganisms, mainly Gardnerella vaginalis, Mobiluncus, Bacteroides spp, and Mycoplasma hominis [2]. ...
One of the most frequent causes of irregular vaginal discharge in pregnant women is bacterial vaginosis (BV), which is characterized by a rise of various anaerobic bacteria and a decrease in important bacteria, the lactobacilli. The variation in the prevalence and its contributing causes among various populations, and nations is well known. Hence, in this study, the prevalence and characteristics associated with BV in pregnant women were determined. Descriptive cross-sectional study was conducted on pregnant women who visited the obstetric and gynecological units at Bonga general hospital in Bonga, south west Ethiopia. Nugent"s scoring method was used for the diagnosis of BV. The prevalence of BV was 19.7% (48/244) [95% CI 17.2-23.2]. Vaginal douching with soap was significantly linked to BV in women (AOR, 3.6; 95% CI: 1.4-9.1). Pregnant women with vaginal discharge and with a foul-smelling odor were four times more likely to have BV (AOR, 4.2; 95% CI: 1.7-10.3; p = 0.001). Furthermore, women who had multiple sexual partners were three times more likely to get BV. It was noted that pregnant women in this study had a high prevalence of BV. We revealed that the majority of women with BV had vaginal discharge and an unpleasant odor. We were able to verify the association between BV in pregnant women with multiple sexual partners and women who practiced vaginal douching with soap. Therefore, additional research may be required to validate and assess the reason for this correlation. Planning a preventive approach for BV that discourages vaginal douching with soap and multiple sexual partners during pregnancy may reduce the prevalence of BV.
... UTIs constitute a major risk factor for ectopic pregnancy due to fallopian tube scarring [98,99]. Second, some of the aforementioned non-Lactobacillus species produce sialidase, a virulence factor that makes pregnant women vulnerable to ascending infections and consequent inflammation and fibrosis of the reproductive tract [100,101]. ...
Background/Objectives: There are indications that the microbial composition of the maternal mucosal surfaces is associated with adverse events during pregnancy. The aim of this review is to investigate the link between vaginal microbiome alterations and gestational complication risk. Methods: This comprehensive literature review was performed using Medline and Scopus databases. The following search algorithm was used, “Pregnancy Complications” [Mesh] AND (Vagin*), and after the literature screening, 44 studies were included in the final review. Results: The studies that were included investigated the association between vaginal microbial composition and preterm birth, miscarriage, preeclampsia, ectopic pregnancy, gestational diabetes mellitus, chorioamnionitis, and preterm premature rupture of membranes. In most of the studies, it was well established that increased microbial diversity is associated with these conditions. Also, the depletion of Lactobacillus species is linked to most of the gestational complications, while the increased relative abundance and especially Lactobacillus crispatus may exert a protective effect in favor of the pregnant woman. Several pathogenic taxa including Gardnerella, Prevotella, Sneathia, Bacterial Vaginosis-Associated Bacteria-2, Atopobium, and Megasphera seem to be correlated to higher maternal morbidity. Conclusions: Vaginal microbiome aberrations seem to have an association with pregnancy-related adverse events, but more high-quality homogenous studies are necessary to reliably verify this link.
Objective
To describe the microbiome of the vagina and fallopian tubes (FT) and its relation with hydrosalpinx.
Methods
Case–control study was conducted in women who underwent salpingectomy for hydrosalpinx (case) or other indications (controls). Samples were obtained during surgery and subjected to 16S rRNA amplicon sequencing, and analyses of alpha diversity and beta diversity measures were compared between sites and groups. Differential abundance of bacteria associated with vaginal dysbiosis was compared between cases and controls.
Results
Nine women with hydrosalpinx and 23 women without hydrosalpinx were included in the study. The mean age of studied women was 41 (range: 29–54) and most (89%) were premenopausal. After in silico decontamination, only 30% of control FT samples and 10% of case FT samples had evidence of bacterial presence. The vaginal microbiome of control patients showed greater abundance of lactobacilli, whereas the vaginal microbiome of case patients contained relatively more bacterial vaginosis-associated bacteria, such as Prevotella and Atopobium. A significant difference was found in alpha and beta diversity between vaginal and FT microbiomes in control patients as FT samples were more diverse. We found that women with hydrosalpinx had a more “dysbiotic” vaginal microbiome and in women without hydrosalpinx, microbial composition within the vagina and FT differed, possibly representing two distinct ecological environments.
Conclusion
Women undergoing salpingectomy for various reasons harbored bacteria within their FT, while women with hydrosalpinx generally did not. This suggests that even though infection may be an underlying cause of hydrosalpinx, bacteria may not be present by the time patients require surgery.
Given the voluminous data regarding the microbiota and human health, this chapter focuses on exemplar data to highlight key findings that are often generalizable across body sites and disease states. The Human Microbiome Project, a landmark study that cataloged the microbiome in multiple anatomic sites in healthy adults, found that the composition of the microbiota differs by body site, there is tremendous interindividual variation, and the microbial gene content is relatively conserved irrespective of the body site or individual. The oropharyngeal microbiota translocates to the lower respiratory tract via normal microaspirations in healthy individuals. The ileal microbiota contains a number of Streptococcus spp. and other bacteria that are also found in the oral microbiota, a finding that suggests some continuity of microbes throughout the gastrointestinal tract. The skin microbiome is a diverse ecosystem with the greatest variation in microbial species over time and the greatest phylogenetic diversity of all anatomic sites.
Background
Women with vulvovaginal candidiasis (VVC) are known to experience vaginal microbial dysbiosis. However, the dynamic alterations of the vaginal microbiome in pregnant women with VVC and its effect on neonatal gut microbiome remain unclear. This study aims to characterize the vaginal microbiome in pregnant women with VVC and its impact on their offspring’s meconium microbiome.
Methods
Forty-four pregnant women, including 17 with VVC (VVC group) and 27 healthy controls (HC group), along with their 44 offspring, were enrolled in this study. Maternal vaginal samples were collected during the pre- and post-delivery phases. Meconium samples from their newborns were also obtained. Microbial communities were characterized using 16S rRNA sequencing.
Results
The vaginal microbiome of healthy pregnant women was predominantly composed of the genus Lactobacillus. The Bray-Curtis dissimilarity index indicated significant alterations in the vaginal microbiome of the VVC group, with a notable decrease in Lactobacillus and significant increases in Delftia, Burkholderia during both the pre- and post-delivery phases compared to the HC group. Additionally, the neonatal meconium microbiome exhibited significant differences between the VVC and HC groups, with L. salivarius and L. helveticus significantly decreased and Delftia significantly increased in the VVC group. Similar trends in microbial variation were observed across maternal and neonatal microbiomes, indicating intergenerational concordance associated with VVC.
Conclusion
VVC alters the microbiota of both pregnant women and their neonates at birth, suggesting a form of microbial inheritance. These findings underscore the distinctive characteristics of the vaginal microbiome associated with VVC and its potential impact on the formation of early-life gut microbiome.
The role of microbes inhabiting various body sites in supporting host physiology and health is substantial, and recent advancements in DNA sequencing technology have facilitated a more in-depth understanding of these microbial contributions. The influence of microbiota within a given organ can be broadly categorized as having two main functions: (1) promoting organ homeostasis and (2) creating conditions that inhibit the growth of pathogenic microorganisms, thereby protecting the host from diseases. In livestock production, numerous phenotypes critical to industry outcomes are affected by the microbiome, which has sparked considerable academic interest in recent years. This review aims to analyze the extensive data available on the microbiomes of humans and other mammalian species, examining microbiome ecology to elucidate principles that may assist in interpreting data on livestock microbiomes. Additionally, the review will discuss techniques available for investigating various microbiome aspects and will examine existing data on the reproductive microbiome, with a particular focus on the bovine vaginal microbiome.
1) Background: Microbiota could be related to tumorigenesis through the persistence of an inflammatory state, also at the endometrial level. Inflammation, in fact, is involved in the promotion of genetic instability and in a favorable microenvironment for tumor growth. One pathway could be the disruption of the epithelial/mucosal barrier, with the activation of cytokines. The microbiota also seem to favor other involved patterns, such as insulin resistance and increased adipose tissue. (2) Methods: The online search for this review was based on keywords such as "endometrial cancer" and "microbiota" on the main online scientific database. Our objective is a narrative up-to-date review of the current literature on gynecological microbiota; we analyze the possible correlations with known modifying and promoting oncological factors (i.e., Body Mass Index-BMI, menopause, pH), with particular attention to vaginal and uterine microorganisms respective to the development of endometrial cancer in comparison to healthy women. (3) Results: Various species and distributions of bacteria could be related to tumorigenesis and induce alterations in cell signaling and cycle pathways, including those in the gynecological field. (4) Conclusions: In the literature, the different composition of uterine and vaginal microbiota has been analyzed in the past years, and their diversity and actions seem to correlate with possible oncological effects.
Background. The problem of extremely early premature birth (ERP) is one of the most urgent in obstetrics due to the unfavorable perinatal prognosis and consequences for the mother’s body. At the same time, in the postpartum period, the patient is threatened with infectious and inflammatory complications due to infection prior to childbirth, a decrease in uterine contractility, and prolonged inpatient stay in connection with the care of an extremely premature newborn.
Objective. Assessment of changes in the microbiota of the vagina and cervical canal in women in the dynamics of the first month after extremely early premature birth.
Materials and methods. The main group consisted of women who delivered at 22-27/6 weeks gestation (N=50).The control group consisted of 50 patients who were delivered during full-term pregnancy. The patients underwent bacteriological studies of the contents of the cervical canal and studies of the biocenosis of the vagina by PCR (Femoflor-16). The studies were conducted on the 3rd and 30th days after childbirth.
Results. The microbiota of the lower genital tract of women after extremely early premature birth undergoes the following changes: by the 30th day of the postpartum period, there was a statistically significant increase in the proportion of conditionally pathogenic microflora, mainly represented by gram-positive flora (Staphylococcus spp, Streptococcus spp, Enterococcus faecalis), however, with the development of infectious and inflammatory complications, the proportion of gram-negative microflora increases (Escherichia coli). In the study of vaginal biocenosis, it was found that in the dynamics of the postpartum period in patients after extremely early premature birth, the proportion of aerobic dysbiotic disorders decreases, and the proportion of moderate and pronounced anaerobic dysbiosis increases more than twice.
Conclusion. It is necessary to search for effective methods of preventing postpartum complications of bacterial nature in patients after extremely early premature birth, taking into account the transformation of the microbiota of the lower parts during the first month after childbirth.
Background
The female genital tract microbiome has become a particular area of interest in improving assisted reproductive technology (ART) outcomes with the emergence of next-generation sequencing (NGS) technology. However, NGS assessment of microbiomes currently lacks uniformity and poses significant challenges for accurate and precise bacterial population representation.
Objective
As multiple NGS platforms and assays have been developed in recent years for microbiome investigation—including the advent of long-read sequencing technologies—this work aimed to identify current trends and practices undertaken in female genital tract microbiome investigations.
Results
Areas like sample collection and transport, DNA extraction, 16S amplification vs. metagenomics, NGS library preparation, and bioinformatic analysis demonstrated a detrimental lack of uniformity. The lack of uniformity present is a significant limitation characterised by gap discrepancies in generation and interpretation of results. Minimal consistency was observed in primer design, DNA extraction techniques, sample transport, and bioinformatic analyses.
Conclusion
With third-generation sequencing technology highlighted as a promising tool in microbiota-based research via full-length 16S rRNA sequencing, there is a desperate need for future studies to investigate and optimise methodological approaches of the genital tract microbiome to ensure better uniformity of methods and results interpretation to improve clinical impact.
Graphical Abstract
Objective
To compare the vaginal microbiota of premenopausal and postmenopausal women and postmenopausal women undergoing menopausal hormone therapy (MHT) and examine the association between vaginal microbiota and genitourinary syndrome of menopause (GSM).
Methods
This cross-sectional study classified 94 women aged 40 to 60 years into three groups: premenopausal (Pre, n = 32), postmenopausal (Post, n = 30), and postmenopausal women who received MHT orally (Post + MHT, n = 32). Neither the Pre nor the Post group received hormone therapy within the past 6 months. Postmenopausal women who received vaginal MHT were not included. Vaginal swabs were obtained, and microbial composition was characterized by 16S rRNA gene sequencing targeting the V3 to V4 region. Clinical data were collected and serum sex hormones were measured. The most bothersome symptom approach and vaginal health index were used to evaluate GSM. Mann-Whitney U or Kruskal-Wallis ANOVA followed by multiple comparison tests were performed for comparison between or across groups. The correlations between GSM symptom scores and vaginal microbiota were determined using Spearman's correlation analysis.
Results
The vaginal community of postmenopausal women was characterized by a decreased abundance of Lactobacillus (Post 18% vs Pre 69%); an increased abundance of several anaerobic bacteria, including Prevotella , Escherichia-Shigella , and Bifidobacterium ; and a higher microbial diversity ( P < 0.001 for Shannon and Simpson indexes) than those of premenopausal women. The vaginal community of postmenopausal women who received MHT had an increased abundance of Lactobacillus (54%) and lower microbial diversity ( P < 0.001 for Shannon and Simpson indexes) than the postmenopausal women. The vaginal microbial community composition of the Pre group shared more similarity with that of the Post + MHT group (Adonis P = 0.051) than with that of the Post group (Adonis P < 0.001). A decreased abundance of Lactobacillus and high diversity in the vaginal community were found in women with moderate to severe GSM symptoms.
Conclusions
Among Chinese postmenopausal women, those receiving MHT had higher Lactobacillus abundance but lower abundance of diverse anaerobes and diversity of the vaginal microbial community compared to non-MHT women. MHT in postmenopausal women may potentially contribute to reestablishing vaginal microbiota homeostasis. Findings in this pilot study, however, need to be examined in larger, prospective studies.
Periodontitis-related oral microbial dysbiosis is thought to contribute to adverse pregnancy outcomes (APOs), infertility, and female reproductive inflammation. Since probiotics can modulate periodontitis and oral microbiome dysbiosis, this study examined the effects of a probiotic bacteriocin, nisin, in modulating the reproductive microbiome and inflammation triggered by periodontitis. A total of 24 eight-week-old BALB/cByJ female mice were randomly divided into four treatment groups (control, infection, nisin, and infection+nisin group), with 6 mice per group. A polymicrobial (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum) mouse model of periodontal disease was used to evaluate the effects of this disease on the female reproductive system, with a focus on the microbiome, local inflammation, and nisin’s therapeutic potential in this context. Moreover, 16s RNA sequencing was used to evaluate the changes in the microbiome and RT-PCR was used to evaluate the changes in inflammatory cytokines. Periodontal pathogen DNA was detected in the reproductive organs, and in the heart and aorta at the end of the experimental period, and the DNA was especially elevated in the oral cavity in the infection group. Compared to the control groups, only P. gingivalis was significantly higher in the oral cavity and uterus of the infection groups, and T. forsythia and F. nucleatum were significantly higher in the oral cavity of the infection groups. The infection and nisin treatment group had significantly lower levels of P. gingivalis, T. forsythia, and F. nucleatum in the oral cavity compared with the infection group. Since periodontal pathogen DNA was also detected in the heart and aorta, this suggests potential circulatory system transmission. The polymicrobial infection generally decreased the microbiome diversity in the uterus, which was abrogated by nisin treatment. The polymicrobial infection groups, compared to the control groups, generally had lower Firmicutes and higher Bacteroidota in all the reproductive organs, with similar trends revealed in the heart. However, the nisin treatment group and the infection and nisin group, compared to the control or infection groups, generally had higher Proteobacteria and lower Firmicutes and Bacteroidota in the reproductive organs and the heart. Nisin treatment also altered the microbiome community structure in the reproductive tract to a new state that did not mirror the controls. Periodontal disease, compared to the controls, triggered an increase in inflammatory cytokines (IL-6, TNF-α) in the uterus and oral cavity, which was abrogated by nisin treatment. Polymicrobial periodontal disease alters the reproductive tract’s microbial profile, microbiome, and inflammatory status. Nisin modulates the microbial profile and microbiome of the reproductive tract and mitigates the elevated uterine inflammatory cytokines triggered by periodontal disease.
Background
We previously reported the effect of contraception on cervical tenofovir concentrations in Ugandan women living with HIV. Here we explored the role of cervicovaginal cytokines and drug metabolizing enzymes and transporters (DMETs) to elucidate FGT drug disposition in a Ugandan cohort.
Methods
Cervicovaginal fluid and cervical biopsies were collected from Ugandan women living with HIV receiving tenofovir/lamivudine-based therapy and intramuscular depot medroxyprogesterone acetate (DMPA-IM; n=25), copper IUD (cuIUD; n=12), or condoms (n=13) as contraception. Cytokines were measured in cervicovaginal fluid (CVF). Ectocervical tenofovir diphosphate (TFVdp) and lamivudine triphosphate (3TCtp), dATP/dCTP concentrations, and immune marker/DMETs gene expression were measured in cervical biopsies.
Results
Cervical 3TCtp was not correlated with any CVF cytokines. Cervical TFVdp was correlated with IL-10, IL-7, and IL-17 in CVF. CCR5 mRNA expression in cervical biopsies was higher in cuIUD-users versus condoms-users. Using multivariable linear regression, CVF IL-17, tissue dATP, plasma estradiol, and plasma tenofovir were all significant predictors of cervical TFVdp. Tissue dCTP and plasma lamivudine were significant predictors of cervical 3TCtp.
Conclusions
TFVdp concentrations in cervix appear to be influenced by local inflammation. In contrast, 3TCtp FGT exposure was not affected by genital inflammation or DMETS. CuIUD users have more immune cells present, which may in turn influence local TFVdp disposition.
The female reproductive tract microbiota is a complex community of microorganisms that might be crucial in maintaining a healthy reproductive environment. Imbalances in the bacterial community (dysbiosis) and the reduction of beneficial organisms and pathogen proliferation are associated with disease. Endometritis is a common cause of fertility problems in mares, and it is still challenging to diagnose and treat based on routine culture results of certain microorganisms. Although high-throughput sequencing studies provide helpful information regarding the composition of the reproductive tract microbiota in mares, there are still challenges in defining a “normal” microbiota. The primary objective of this literature review is to summarize the current knowledge regarding the microbiota present in the reproductive tract of mares, including the vagina, cervix, and uterus. The second objective is to describe the relevant factors that can impact the reproductive microbiota of mares, including the estrous cycle stage, the type of species (genera) investigated, season, and geographic location. The rationality of identifying the normal microbiota in the reproductive tract of a mare will likely aid in understanding the impact of the microbiota on the host’s reproductive health and contribute to the treatment and prevention of equine sub and infertility issues.
The emergence of new infectious diseases poses a major threat to humans, animals, and broader ecosystems. Defining factors that govern the ability of pathogens to adapt to new host species is therefore a crucial research imperative. Pathogenic bacteria are of particular concern given dwindling treatment options amid the continued expansion of antimicrobial resistance. In this review we summarize recent advancements in the understanding of bacterial host species adaptation, with an emphasis on pathogens of humans and related mammals. We focus particularly on molecular mechanisms underlying key steps of bacterial host adaptation including colonization, nutrient acquisition, and immune evasion, as well as suggest key areas for future investigation. By developing a greater understanding of the mechanism underlying host adaptation in pathogenic bacteria, we may uncover new strategies to target these microbes for the treatment and prevention of infectious diseases in humans, animals, and the broader environment.
Purpose
This study aimed to demonstrate the correlation between altered balance of the vaginal ecosystem and increased risk of vaginitis, bacterial vaginosis, and sexually transmitted diseases and the association between specific alterations found in fresh bacterioscopic examinations (FBE) and the risk of certain infections.
Methods
A retrospective, monocentric study was conducted from January 2013 to December 2023. Patients who underwent FBE and vaginal swabs following reported symptoms or suspected syndromic pictures of vulvovaginal infections were included.
Results
Two thousand one hundred ten patients were included and divided into a control group (n = 811, 38.4%) and a pathological group (n = 1299 patients, 61.6%), based on the presence of alterations at the FBE. In the pathological group, 1185 women (91% of positive FBE) had vaginal infections detected through vaginal swabs. The presence of lactobacilli and typical inflammatory cells was detected in 111 (8%) women with pathological FBE and correlated with higher rates of positive swabs for common germs (n = 104, 94%), often leading to co-infections (n = 30, 29%). Conversely, Döderlein’s cytolysis (n = 56, 4.3% of positive FBE) indicated a predominance of positive human papillomavirus (HPV) swabs (n = 33, 59%). The presence of fungal elements (n = 208, 16% of positive FBE) suggested a higher prevalence of co-infections (n = 62, 30%). Similarly, mixed bacterial flora (n = 470, 36% of positive FBE) and Trichomonas vaginalis (n = 11, 0.8% of positive FBE) correlated with positive swabs for other pathogens, except for Mycoplasma (n = 0). Bacterial vaginosis (n = 443, 34% of positive FBE) was linked to co-infections (n = 142, 32%) and HPV (n = 123, 28%).
Conclusion
The importance of conducting FBE in patients with vulvovaginal symptoms is emphasized. This approach aids in determining the need for further diagnostic tests like vaginal swabs, guided by microscopic findings. A strong correlation emerges between the presence of specific alterations in the FBE and an increased prevalence of certain infections.
OBJECTIVE
It was recently discovered that the microbiota has a significant impact on pregnancy, gynecological, and neonatal health. However, studies indicate that people struggle to understand topics, such as microbiota, microbiome, probiotics, and prebiotics, or comprehend them inaccurately or incompletely. Understanding the human microbiota and probiotics that can regulate the microbiota helps women develop daily habits for both healthy nutrition and health protection. The aim of this study was to assess the microbiota awareness levels of women who are planning pregnancy.
METHODS
A cross-sectional descriptive study was carried out on 417 women who were planning pregnancy. Face-to-face interviews and questionnaires were used to collect research data. A microbiota awareness scale was used as a data collection tool.
RESULTS
The study found a statistically significant difference in the subdimension scores related to microbiota awareness, general information, product knowledge, chronic disease, and probiotic and prebiotic knowledge based on the educational status of the participants. The study concluded that the participants had a confusion about microbiota awareness, general information, product information, chronic disease, and probiotic and prebiotic subdimensions. Furthermore, it was found that the participants had only a partial understanding of the relationship between microbiota and diseases.
CONCLUSION
It is recommended that training programs focusing on the relationship between microbiota and health in women, such as "microbiota and its importance in women's health" and "microbiota and disease relationship," be organized and women would be encouraged to participate in these training programs.
Introduction. Statistics show that about 13 to 15 in 100 pregnancies end in early miscarriage. This represents both a medical and social issue, as such outcome may be associated with maternal depression and anxiety, which inevitably affects women’s activities, performance efficiency and social inclusion. Restoration of normobiocenosis and lactobacilli pool dominance is one of the key challenges for women planning pregnancy.
Aim. To evaluate the effectiveness of probiotics at the pregravid preparation stage in women with a history of early pregnancy loss and bacterial vaginosis (BV).
Materials and methods. We selected 46 patients of reproductive age (24–39 years) who applied for early pregnancy loss, with complaints of vaginal discharge with an unpleasant odour, pruritus, burning, and dyspareunia, using databases of 5 medical clinics in Moscow, Tyumen and Stavropol. To treat bacterial vaginosis, two-stage therapy aimed at eliminating the increased number of anaerobic microorganisms and restoring the vaginal microbiocenosis was used.
Results. The effectiveness of combination therapy was assessed at 1 month. All patients on therapy experienced clinical improvement, normalization of vaginal microbiocenosis parameters based on Femoflor-16 test findings after the end of treatment. Physiological microbiocenosis of Lactobacillus spp. > 107 was detected in 43 (94.5%). In all patients, the average vaginal pH after two-stage therapy was 4.3 ± 0.7. The safety of Acilact Duo therapy was assessed in all study participants. No negative trends were recorded.
Conclusion. Superlimflife (Acilact Duo), acidophilus bacteria + vitamin-mineral protein-peptide complex, quickly restores optimal vaginal acidity (pH), stimulates the growth of lactobacilli, and reduces the incidence of BV relapses.
目的
开发基于深度学习的人工智能阴道分泌物分析系统，评估自动化镜检对需氧菌性阴道炎（aerobic vaginitis, AV）临床诊断的准确性。
方法
选取2020年1月–2021年12月就诊于四川大学华西第二医院妇产科3769例患者的阴道分泌物，以人工镜检结果为对照，通过Python Scikit-learn script开发出能识别含中毒颗粒白细胞和基底旁上皮细胞（parabasal epitheliocytes, PBC）的人工智能自动化分析软件（linear kernel SVM algorithm），并利用乳杆菌和AV常见分离菌的标准菌株重新设置细菌分级参数。以人工镜检结果为对照，得到人工智能判断AV评分中各项目各分值之间的受试者工作特征（receiver operating characteristic, ROC）曲线和cut-off值，从而设定出自动化判读AV的参数，初步建立AV自动化分析评分方法。
结果
共收集到3769份阴道分泌物标本。人工智能识别AV共有5个参数，每个参数有3种程度。乳杆菌与AV常见菌的直径分界值为1.5 μm，乳杆菌的自动化判断参数是长径≥1.5 μm∶<1.5 μm细菌的比值，分界值是2.5 和0.5 ；白细胞（white blood cell, WBC）的自动化判断参数中，WBC绝对数量的分界值是103 μL－1，WBC/上皮细胞的比值分界值是10；含中毒颗粒白细胞的自动化判断参数是含中毒颗粒WBC/WBC比值，分界值是1%和15%；背景菌落的自动化判断参数是<1.5 μm，细菌分界值是5×103 μL－1和3×104 μL－1，PBC的自动化判断参数是PBC/上皮细胞的比值，分界值是1%和10%。自动化镜检与人工镜检的一致率为92.5%，200例标本中评分一致的有185例，不一致有15例。
结论
本研究开发的人工智能AV识别软件，其建立的阴道分泌物AV自动化镜检评分方法，检测结果与人工镜检具有较好的一致性，可较为客观、敏感、高效完成临床检验，并降低人工镜检工作负荷。
Vaginal microbiota transplantation (VMT) is a cutting-edge treatment modality that has the potential to revolutionize the management of vaginal disorders. The human vagina is a complex and dynamic ecosystem home to a diverse community of microorganisms. These microorganisms play a crucial role in maintaining the health and well-being of the female reproductive system. However, when the balance of this ecosystem is disrupted, it can lead to the development of various vaginal disorders. Conventional treatments, such as antibiotics and antifungal medications, can temporarily relieve the symptoms of vaginal disorders. However, they often fail to address the underlying cause of the problem, which is the disruption of the vaginal microbiota. In recent years, VMT has emerged as a promising therapeutic approach that aims to restore the balance of the vaginal ecosystem. Several studies have demonstrated the safety and efficacy of VMT in treating bacterial vaginosis, recurrent yeast infections, and other vaginal conditions. The procedure has also shown promising results in reducing the risk of sexually transmitted infections and preterm birth in pregnant women. However, more research is needed to establish optimal donor selection, preparation, and screening protocols, as well as long-term safety and efficacy. VMT offers a safe, effective, and minimally invasive treatment option for women with persistent vaginal problems. It could improve the quality of life for millions of women worldwide and become a standard treatment option shortly. With further research and development, it could potentially treat a wide range of other health problems beyond the scope of vaginal disorders.
Introduction
Previous research has linked vaginal bacteria to polycystic ovary syndrome (PCOS) and obesity in women, yet the specific disparities in vaginal microbiota between these conditions remain unclear.
Methods
In this study, we aimed to elucidate the contribution of dysregulated vaginal microbiota to PCOS and obesity by analyzing the vaginal microbiota in reproductive-aged women with and without PCOS, as well as obese and non-obese women, using shotgun sequencing.
Results
Swab specimens were collected from four groups of subjects: PCOS and obese, PCOS and non-obese, non-PCOS and obese, and non-PCOS and non-obese. A total of 333 bacteria and 24 viruses/phages were identified to the species level. Clustering analysis revealed that non-PCOS and non-obese individuals exhibit a similar “healthy” vaginal microbiome, while both obesity and PCOS were associated with microbial dysbiosis. Significant differences in abundance were observed for 26 bacterial species and 6 phages/viruses between groups. Notably, pathobionts such as Streptococcus pyogenes , Leptospira santarosai , Citrobacter amalonaticus , Listeria ivanovii , and Clostridium perfringens were significantly less abundant or absent in the non-PCOS and non-obese group. Furthermore, the abundance of Lactobacillus , Pseudomonas bacteria, and their corresponding phages exhibited positive correlations. Lactobacillus bacteria, lactobacillus phage, and pseudomonas phage/virus were identified as indicators of a healthy vaginal microbiome. Importantly, the differentially enriched bacteria in the PCOS and obesity groups were distinct.
Discussion
This study confirms that PCOS and obesity are associated with differing enrichment of bacteria and viruses/phages, with both conditions linked to microbial dysbiosis. Moreover, our findings suggest that vaginal phage diversity is associated with a healthy vaginal microbiota, while dysbiosis is associated with a decrease in phages alongside increased bacterial diversity.
The intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host–microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances in microbiota composition (dysbiosis) are associated with a plethora of human diseases and are believed to modulate disease initiation, progression and therapy response. The vast complexity of the human microbiota and its metabolic output represents a great challenge in unraveling the molecular basis of host–microbe interactions in specific physiological contexts. To increase our understanding of these interactions, functional microbiota research using animal models in a reductionistic setting are essential. In the dynamic landscape of gut microbiota research, the use of germ‐free and gnotobiotic mouse technology, in which causal disease‐driving mechanisms can be dissected, represents a pivotal investigative tool for functional microbiota research in health and disease, in which causal disease‐driving mechanisms can be dissected. A better understanding of the health‐modulating functions of the microbiota opens perspectives for improved therapies in many diseases. In this review, we discuss practical considerations for the design and execution of germ‐free and gnotobiotic experiments, including considerations around germ‐free rederivation and housing conditions, route and timing of microbial administration, and dosing protocols. This comprehensive overview aims to provide researchers with valuable insights for improved experimental design in the field of functional microbiota research.
Lactobacillus johnsonii is a commensal bacterium that has been isolated from vaginal and gastrointestinal (GI) tracts of vertebrate hosts, including humans, rodents, swine, and poultry. Lactobacillus -based probiotic supplements are popular because of the health advantages they offer. Species such as L. johnsonii are particularly interesting due to their potential health-promoting properties. Here, we reviewed the research on specific strains of L. johnsonii that have been studied in the context of health and disease and delved into the underlying mechanisms that aid in preserving host homeostasis. The utilization of L. johnsonii strains has been widely linked to numerous health benefits in the host. These include pathogen antagonism, control of mucosal and systemic immune responses, reduction of chronic inflammation, modulation of metabolic disorders, and enhanced epithelial barrier. These findings suggest that L. johnsonii plays a critical role in maintaining host homeostasis, highlighting its potential as a probiotic.
Introduction
This study used an unsupervised machine learning algorithm, sidClustering and random forests, to identify clusters of risk behaviors of Bacterial Vaginosis (BV), the most common cause of abnormal vaginal discharge linked to STI and HIV acquisition.
Methods
Participants were 391 cisgender women in Miami, Florida, with a mean of 30.8 (SD = 7.81) years of age; 41.7% identified as Hispanic; 41.7% as Black and 44.8% as White. Participants completed measures of demographics, risk behaviors [sexual, medical, and reproductive history, substance use, and intravaginal practices (IVP)], and underwent collection of vaginal samples; 135 behavioral variables were analyzed. BV was diagnosed using Nugent criteria.
Results
We identified four clusters, and variables were ranked by importance in distinguishing clusters: Cluster 1: nulliparous women who engaged in IVPs to clean themselves and please sexual partners, and used substances frequently [n = 118 (30.2%)]; Cluster 2: primiparous women who engaged in IVPs using vaginal douches to clean themselves (n = 112 (28.6%)]; Cluster 3: primiparous women who did not use IVPs or substances [n = 87 (22.3%)]; and Cluster 4: nulliparous women who did not use IVPs but used substances [n = 74 (18.9%)]. Clusters were related to BV (p < 0.001). Cluster 2, the cluster of women who used vaginal douches as IVPs, had the highest prevalence of BV (52.7%).
Conclusions
Machine learning methods may be particularly useful in identifying specific clusters of high-risk behaviors, in developing interventions intended to reduce BV and IVP, and ultimately in reducing the risk of HIV infection among women.
The aim of our study was to retrospectively evaluate whether the oral administration of L. crispatus (M247) could increase pregnancy and live birth rates in women undergoing assisted reproductive technology procedures. Enrolled women (N = 160) were divided into two groups: treated (N = 80) or untreated (N = 80) with the probiotic strain. The odds ratio (OR) for a treated woman to have a clinical pregnancy (CP) was 1.56. In women aged 30-40 years, M247 increased the probability of a CP in correlation with the progressive rise in BMI, reaching 47% (35% in controls) with a BMI of 35 (OR: 2.00). The CAID statistics showed that in a woman of the blastocyst subgroup, below 43 years, with a BMI over 18.6, treatment with M247 increased the chance of a CP from 28.4% to 44.5% (OR: 2.08; p < 0.05). Considering live births, the rate of the probiotic group was 12.5% versus 7.5% (OR: 1.76). Considering only the blastocyst subgroup, the treatment increased the number of live births by 200% (OR: 3.64; p = 0.05). As confirmed also by statistical indices NNT, NNH, and LHH, the use of M247 demonstrated a risk-benefit ratio to the full advantage of the benefits.
The vaginal microecology comprises the vaginal microbiome, immune microenvironment, vaginal anatomy, and the cervicovaginal fluid, which is rich in metabolites, enzymes, and cytokines. Investigating its role in the female reproductive system holds paramount significance. The advent of next‐generation sequencing enabled a more profound investigation into the structure of the vaginal microbial community in relation to the female reproductive system. Human papillomavirus infection is prevalent among women of reproductive age, and persistent oncogenic HPV infection is widely recognized as a factor associated with cervical cancer. Extensive previous research has demonstrated that dysbiosis of vaginal microbiota characterized by a reduction in Lactobacillus species, heightens susceptivity to HPV infection, consequently contributing to persistent HPV infection and the progression of cervical lesion. Likewise, HPV infection can exacerbate dysbiosis. This review aims to provide a comprehensive summary of current literatures and to elucidate potential mechanisms underlying the interaction between vaginal microecology and HPV infection, with the intention of offering valuable insights for future clinical interventions.
Dysbiosis of the female reproductive tract is closely associated with gynecologic diseases. Here, we aim to explore the association between dysbiosis in the genital tract and uterine fibroids (UFs) to further provide new insights into UF etiology. We present an observational study to profile vaginal and cervical microbiome from 29 women with UFs and 38 healthy women, and 125 samples were obtained and sequenced. By comparing the microbial profiles between different parts of the reproductive tract, there is no significant difference in microbial diversity between healthy subjects and UF patients. However, alpha diversity of UF patients was negatively correlated with the number of fibroids. Increased Firmicutes were observed in both the cervical and vaginal microbiome of UF patients at the phylum level. In differential analysis of relative abundance, some genera were shown to be significantly enriched (e.g., Erysipelatoclostridium, Mucispirillum, and Finegoldia) and depleted (e.g., Erysipelotrichaceae UCG-003 and Sporolactobacillus) in UF patients. Furthermore, the microbial co-occurrence networks of UF patients showed lower connectivity and complexity, suggesting reduced interactions and stability of the cervical and vaginal microbiota in UF patients. In summary, our findings revealed the perturbation of microbiome in the presence of UFs and a distinct pattern of characteristic vaginal and cervical microbiome involved in UFs, offering new options to further improve prevention and management strategies.
Introduction
Menstrual cups (MC) are a reusable feminine hygiene product. A recent publication suggested that Staphylococcus aureus ( S. aureus ) biofilms can form on MCs which may lead to increased risk of menstrual Toxic Shock Syndrome (mTSS). Additionally, there is concern that buildup of residual menses may contribute to microbial growth and biofilm formation further increasing mTSS risk. Quantitative and qualitative analysis of in vitro tests were utilized to determine if S. aureus biofilm could form on MC in the presence of the keystone species Lactobacillus after 12 h of incubation. The methodology was based on a modification of an anaerobic in vitro method that harnesses the keystone species hypothesis by including a representative of vaginal lactic acid bacteria.
Methods
MCs were incubated anaerobically for 12 h in Vaginal Defined Media (VDM) with the two morphologically distinct bacteria, Lactobacillus gasseri ( L. gasseri ) and S. aureus . Colony Forming Units (CFU) for each organism from the VDM broth and sonicated MC were estimated. In addition, a separate experiment was conducted where S. aureus was grown for 12 h in the absence of L. gasseri . Qualitative analysis for biofilm formation utilized micro-CT (µ-CT) and cryogenic scanning electron microscopy (Cryo-SEM).
Results
Samples collected from the media control had expected growth of both organisms after 12 h of incubation. Samples collected from VDM broth were similar to media control at the end of the 12-h study. Total S. aureus cell density on MC following sonication/rinsing was minimal. Results when using a monoculture of S. aureus demonstrated that there was a significant growth of the organism in the media control and broth as well as the sonicated cups indicating that the presence of L. gasseri was important for controlling growth and adherence of S. aureus . Few rod-shaped bacteria ( L. gasseri) and cocci ( S. aureus) could be identified on the MCs when grown in a dual species culture inoculum and no biofilm was noted via µ-CT and cryo-SEM. Additionally, efforts to model and understand the validity of the current labeled recommendations for MC cleaning in-between uses are supported.
Discussion
The data support continued safe use of the Tampax® cup when used and maintained as recommended.
This study aims to investigate the influence of topical estrogen management in postmenopausal patients who had undergone CO2 laser ablation for vaginal squamous intraepithelial lesions (SILs). The clinical data of 211 postmenopausal women with vaginal SILs were reviewed. Patients were divided into two groups by 2-month different management: Group 1 (intervention group): patients were treated with estrogen cream 0.5 g every other day and Group 2 (control group): no topical agent was used for the treatment of patients. In low-grade squamous intraepithelial lesions (LSILs), the response rates for patients in the intervention group and the control group were 49.1% (27/55) and 54.2% (16/48), respectively; human papillomavirus (HPV) status turned negative in 12 (12/38, 31.6%) patients of the intervention group and in 15 (15/35, 42.9%) patients of the control group. In high-grade squamous intraepithelial lesions (HSILs), the response rates for patients in the intervention group and the control group were 72.4% (42/58) and 78.0% (39/50), respectively, nearly 1.5 times higher than those of the LSIL patients; 22 (22/54, 40.7%) patients of the intervention groups and 12 (12/46, 26.1%) patients of the control group cleared the HPV infection. In postmenopausal patients, local use of estrogen cream improves the recognition of lesions and is conducive to precision medicine.
Background:
The reproductive tract microbiota that evolved as an integrative component has been studied intensively in the last decade. As a result, novel research, clinical opportunities, and perspectives have been derived following the close investigation of this microecological environment. This has paved the way for an update to and improvement of the management strategies and therapeutic approaches. However, obscurities, contradictions, and controversies arise regarding the ascension route from the vagina to the endometrium via the cervix, with finality in adverse obstetric outcomes.
Methods:
Starting from these considerations, we aimed to gather all existing data and information from four major academic databases (PubMed, ISI Web of Knowledge, Scopus, and ScienceDirect) published in the last 13 years (2010-2023) using a controlled vocabulary and dedicated terminology to enhance the coverage, identification, and sorting of potentially eligible studies.
Results:
Despite the high number of returned entries (n = 804), only a slight percentage (2.73%) of all manuscripts were deemed eligible following two rounds of evaluation. Cumulatively, a low level of Lactobacillus spp. and of other core microbiota members is mandatory, with a possible eubiosis-to-dysbiosis transition leading to an impairment of metabolic and endocrine network homeostasis. This transposes into a change in the pro-inflammatory landscape and activation of signaling pathways due to activity exerted by the bacterial lipopolysaccharides (LPSs)/endotoxins that further reflect a high risk of miscarriage in various stages. While the presence of some pathogenic entities may be suggestive of an adverse obstetric predisposition, there are still pros and cons of the role of specific strains, as only the vagina and cervix have been targeted as opposed to the endometrium, which recently started to be viewed as the key player in the vagina-cervix-endometrium route. Consequently, based on an individual's profile, diet, and regime, antibiotics and probiotics might be practical or not.
Conclusions:
Resident bacteria have a dual facet and are beneficial for women's health, but, at the same time, relaying on the abundance, richness, and evenness that are definitory indexes standing as intermediaries of a miscarriage.
Importance:
Pessary-related adverse effects are common, and treatment options are limited. Probiotics may improve pessary-related adverse effects by altering the vaginal microenvironment.
Objective:
This study aimed to evaluate the effect of a vaginal probiotic suppository on the vaginal microenvironment among pessary users.
Study design:
Women who used pessaries were randomized to vaginal probiotic suppository use versus without use. The intervention was a vaginal probiotic suppository and moisturizing vaginal gel. The vaginal microenvironment was assessed using Gram stain and Nugent's criteria at baseline and 3 months by a microbiologist blinded to group allocation. Symptoms and experience with use of the probiotic were assessed using questionnaires. The primary outcome was change in lactobacilli count on Nugent subscore at 3 months.
Results:
A total of 147 postmenopausal women were randomized (86 to the intervention arm and 61 to the control arm), and 124 (87.9%) presented for a 3-month follow-up. There was no difference between the arms in age, race, body mass index, and Charlson Comorbidity Index. A majority of participants had the pessary managed by the health care professional (intervention arm vs control arm, 46 [76.7%] vs 55 [68.8%]; P = 0.30). Composition of the vaginal microenvironment did not differ with or without probiotic treatment at 3 months. Bother from vaginal symptoms, including discharge, itching, and discomfort, did not differ between arms. Adverse effects from the intervention were minor, resolved with discontinuation, and occurred at 39.1%.
Conclusion:
Vaginal probiotic suppository use did not affect the composition of the vaginal microenvironment, patient satisfaction, or vaginal symptoms after 3 months of use in pessary users.
Background
Nonhygienic products for managing menstruation are reported to cause reproductive tract infections. Menstrual cups are a potential solution. We assessed whether menstrual cups would reduce bacterial vaginosis (BV), vaginal microbiome (VMB), and sexually transmitted infections (STIs) as studies have not evaluated this.
Methods and findings
A cluster randomized controlled trial was performed in 96 Kenyan secondary schools, randomized (1:1:1:1) to control, menstrual cup, cash transfer, or menstrual cup plus cash transfer. This substudy assessing the impact of menstrual cups on BV, VMB, and STIs, included 6 schools from the control (3) and menstrual cup only (3) groups, both receiving BV and STI testing and treatment at each visit. Self-collected vaginal swabs were used to measure VMB (16S rRNA gene amplicon sequencing), BV (Nugent score), and STIs. STIs were a composite of Chlamydia trachomatis and Neisseria gonorrhoeae (nucleic acid amplification test) and Trichomonas vaginalis (rapid immunochromatographic assay). Participants were not masked and were followed for 30 months. The primary outcome was diagnosis of BV; secondary outcomes were VMB and STIs. Intention-to-treat blinded analyses used mixed effects generalized linear regressions, with random effects term for school. The study was conducted between May 2, 2018, and February 7, 2021. A total of 436 participants were included: 213 cup, 223 control. There were 289 BV diagnoses: 162 among control participants and 127 among intervention participants (odds ratio 0.76 [95% CI 0.59 to 0.98]; p = 0.038). The occurrence of Lactobacillus crispatus–dominated VMB was higher among cup group participants (odds ratio 1.37 [95% CI 1.06 to 1.75]), as was the mean relative abundance of L. crispatus (3.95% [95% CI 1.92 to 5.99]). There was no effect of intervention on STIs (relative risk 0.82 [95% CI 0.50 to 1.35]). The primary limitations of this study were insufficient power for subgroup analyses, and generalizability of findings to nonschool and other global settings.
Conclusions
Menstrual cups with BV and STI testing and treatment benefitted adolescent schoolgirls through lower occurrence of BV and higher L. crispatus compared with only BV and STI testing and treatment during the 30 months of a cluster randomized menstrual cup intervention.
Trial registration
ClinicalTrials.gov NCT03051789.
The female genital tract (FGT) performs several functions related to reproduction, but due to its direct exposure to the external environment, it may suffer microbial infections. Both the upper (uterus and cervix) and lower (vagina) FGT are covered by an epithelium, and contain immune cells (macrophages, dendritic cells, T and B lymphocytes) that afford a robust protection to the host. Its upper and the lower part differ in terms of Lactobacillus spp., which are dominant in the vagina. An alteration of the physiological equilibrium between the local microbiota and immune cells leads to a condition of dysbiosis which, in turn, may account for the outcome of FGT infection. Aerobic vaginitis, bacterial vaginosis, and Chlamydia trachomatis are the most frequent infections, and can lead to severe complications in reproduction and pregnancy. The use of natural products, such as probiotics, polyphenols, and lactoferrin in the course of FGT infections is an issue of current investigation. In spite of positive results, more research is needed to define the most appropriate administration, according to the type of patient.
Human body comprises trillions of microbial cells associated with different parts of the body. The composition of microorganisms is different in all the parts of the body. Skin, oral, respiratory, placental, gut, and vaginal microbiome are well explored and studied for their effect on human health and disease. The largest part of humans, skin contains millions of microorganisms. The largest and diverse microbiome is observed in gut region. Microbiome influences human health by modulating the innate and adaptive immune responses. There is a close connection between human microbiome with health and disease. Microbiome maintains an equilibrium state with the human body through the host–microbial symbiotic associations. The role of microbiome shaping the host immune functions and development is well explored. The balance of host system and microbiome may get altered by external or environmental stimuli like exposure to antibiotics. The frequent imbalance of microbiota is called as dysbiosis leading to pathological conditions. Dysbiosis associated with antibiotic treatment reduces the occurrence and number of commensals from body leading to the invasion of pathogens by breaking the colonization resistance. The restoration of microbiome is necessary to reduce the infections. Bacterial chemical signalling or quorum sensing plays important role in shaping the balance of microbiome, thereby reducing the pathogenic interactions.KeywordsMicrobiotaHostSymbiosisImmune systemDysbiosisInfections
Adverse pregnancy outcomes are the main causes of maternal and neonatal morbidity and mortality, including long-term physical and psychological sequelae. These events are common in low- and middle-income countries, particularly in Sub Saharan Africa, despite national efforts. Maternal infections can cause complications at any stage of pregnancy and contribute to adverse outcomes. Among infections, those of the genital tract are a major public health concern worldwide, due to limited availability of prevention, diagnosis and treatment approaches. This applies even to treatable infections and holds true especially in Sub-Saharan Africa. As late as 2017, the region accounted for 40% of all reported treatable non-viral genital pathogens worldwide, many of which have been independently associated with various adverse pregnancy outcomes, and that include Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Treponema pallidum . Two databases (PubMed and Embase) were examined to identify eligible studies published up to October 2022. This study reviewed findings on the association between infections by treatable non-viral genital pathogens during pregnancy and adverse pregnancy outcomes among women living in Sub-Saharan Africa. Articles' title and abstract were screened at first using keywords as “sexually transmitted infections”, “non-viral”, “adverse pregnancy outcome”, “Africa”, “sub-Saharan Africa”, “pregnant women”, “pregnancy”, and “pregnancy outcome”. Subsequently, according to the eligibility criteria, potential articles were read in full. Results showed that higher risk of preterm birth is associated with Treponema pallidum, Chlamydia trachomatis and Candida albicans infections . Additionally, rates of stillbirth, neonatal death, low birth weight and intrauterine growth restriction are also associated with Treponema pallidum infection . A better insight on the burden of non-viral genital pathogens and their effect on pregnancy is needed to inform antenatal care guidelines and screening programs, to guide the development of innovative diagnostic tools and other strategies to minimize transmission, and to prevent short- and long-term complications for mothers and children.
Background
We investigated the composition and dynamic changes of vaginal microbiota (VM) in pregnant women who underwent in vitro fertilization (IVF), as well as VM in relation to preterm birth.
Methods
Sixteen women who conceived after IVF and 6 women who conceived naturally were recruited to the study. Vaginal samples from all participants were collected in the first, second, and third trimesters of pregnancy (T1, T2 and T3, respectively). The V3–V4 region of 16S rRNA was sequenced to assess the VM.
Results
In all participants, the alpha-diversity indices Chao1 and observed species of VM were significantly higher in T1 compared to T2 and T3. Non-metric multi-dimensional scaling (NMDS) analysis of beta-diversity revealed the VM structure during T1 was significantly different between IVF and control groups, but then gradually converged during T3. A greater abundance of potential pathogenic bacteria and lower abundance of commensal bacteria was observed in the IVF group compared to control group during T1. Moreover, a higher abundance of Lactobacillus_iners, Escherichia_coli and Alloscardovia_omnicolens was found in preterm birth women who underwent IVF.
Conclusions
The VM diversity decreased with increasing gestation in women who underwent IVF and in healthy controls. IVF-induced dysbiosis of the VM occurs mainly during T1 of gestation and may be related to preterm birth.
Vaginal dysbiosis can lead to serious infections in asymptomatic women. Lactobacillus probiotics (LBPs) are being investigated as a promising therapy for reversing vaginal microbiota dysbiosis. This study aimed to investigate whether administering LBPs could improve vaginal dysbiosis and facilitate the colonization of Lactobacillus species in asymptomatic women. 36 asymptomatic women were classified based on the Nugent score as Low-NS (n = 26) and High-NS (n = 10) groups. A combination of Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5, and Lactobacillus reuteri CBT LU4 was administered orally for 6 weeks. The study found that among women with a High-NS, 60% showed improved vaginal dysbiosis with a Low-NS after LBP intake, while four retained a High-NS. Among women with a Low-NS, 11.5 % switched to a High-NS. Genera associated with vaginal dysbiosis were positively correlated with the alpha diversity or NS, while a negative correlation was observed between Lactobacillus and the alpha diversity and with the NS. Vaginal dysbiosis in asymptomatic women with an HNS improved after 6 weeks of LBP intake, and qRT-PCR revealed the colonization of Lactobacillus spp. in the vagina. These results suggested that oral administration of this LBP could improve vaginal health in asymptomatic women with an HNS.
The human microbiota inhabiting different parts of the body has been shown to have a significant impact on human health, with the gut microbiota being the most extensively studied in relation to disease. However, the vaginal microbiota is also an essential commensal microbiota in the female body that plays a crucial role in female health. Despite receiving less attention than gut microbiota, its importance in regulating reproductive immunity and its complex dynamic properties have been increasingly recognized in recent years. Advances in research on the relationship between vaginal microbiota and pregnancy outcomes & gynecological diseases in women have shed light on the importance of maintaining a healthy vaginal microbiota. In this review, we aim to compile recent developments in the study of the vaginal microbial ecosystem and its role in female health and reproductive outcomes. We provide a comprehensive account of the normal vaginal microbiota, the association between the vaginal microbiota and pregnancy outcomes, and the impact of the vaginal microbiota on gynecological diseases in women. By reviewing recent research, we hope to contribute to the advancement of academic medicine’s understanding of the vaginal microbiota’s importance in female health. We also aim to raise awareness among healthcare professionals and the general public of the significance of maintaining a healthy vaginal microbiota for better reproductive health and the prevention of gynecological diseases.
Bacterial vaginosis (BV) is the most common cause of vaginal discharge in reproductive age women. BV has been associated with poor reproductive outcomes like preterm delivery, acquisition of sexually transmitted infections including HIV, and pelvic inflammatory disease. BV represents acquisition of a diverse community of anaerobic and facultative bacteria and a reduction in lactobacilli. It can be diagnosed using several tests ranging from clinical indicators, point-of-care tests, and molecular assays. Molecular technologies are objective, able to detect fastidious bacteria, allow quantitation, and are ideal for self-collected vaginal swabs. This paper reviews currently available BV diagnostic tests in the US.
Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal–infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R² = 0.038), this was not true for neonatal stool (meconium; Mann–Whitney P > 0.05), and there was no observable difference in community function regardless of delivery mode. For infants at 6 weeks of age, the microbiota structure and function had expanded and diversified with demonstrable body site specificity (P < 0.001, R² = 0.189) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery (P = 0.057, R² = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery.
Purpose
The aim of this study was to evaluate the efficacy of fractional CO2 laser therapy in breast cancer survivors as a therapeutic method for vulvovaginal atrophy (VVA) dyspareunia.
Methods
50 patients (mean age 53.3 years) underwent fractional microablative CO2 laser treatment for dyspareunia in oncological menopause (mean time of menopause 6.6 years). The Gloria Bachmann’s Vaginal Health Index (VHI) score was chosen as system to evaluate the presence of VVA and its improvement after the treatment. Intensity of dyspareunia was evaluated using a visual analog scale (VAS).
Results
Data indicated a significant improvement in VVA dyspareunia (p < 1.86e−22) in breast cancer survivors who had undergone 3 sessions of vaginal fractional CO2 laser treatment. Moreover, VHI scores were significantly higher 30 days post-treatment (T4) (p < 0.0001). 76 % of patients were satisfied or very satisfied with the treatment results. The majority (52 %) of patients were satisfied after a long-term follow-up (mean time 11 months). No adverse events due to fractional CO2 laser treatment occurred.
Conclusions
The treatment with fractionated CO2 laser appeared to be a feasible and effective treatment for VVA dyspareunia in breast cancer survivors with contraindications to hormonal treatments.
Exploring large environmental datasets generated by high-throughput DNA sequencing technologies requires new analytical approaches to move beyond the basic inventory descriptions of the composition and diversity of natural microbial communities. In order to investigate potential interactions between microbial taxa, network analysis of significant taxon co-occurrence patterns may help to decipher the structure of complex microbial communities across spatial or temporal gradients. Here, we calculated associations between microbial taxa and applied network analysis approaches to a 16S rRNA gene barcoded pyrosequencing dataset containing 4160 000 bacterial and archaeal sequences from 151 soil samples from a broad range of ecosystem types. We described the topology of the resulting network and defined operational taxonomic unit categories based on abundance and occupancy (that is, habitat generalists and habitat specialists). Co-occurrence patterns were readily revealed, including general non-random association, common life history strategies at broad taxonomic levels and unexpected relationships between community members. Overall, we demonstrated the potential of exploring inter-taxa correlations to gain a more integrated understanding of microbial community structure and the ecological rules guiding community assembly.
Bacterial vaginosis (BV) is characterised by depletion of the normal Lactobacillus spp. and overgrowth of commensal anaerobic bacteria. We investigated the composition of vaginal microbiota and their association with BV in women of reproductive age. Vaginal samples from 1197 women were analysed, whereby n=451 patients had normal flora and n=614 were diagnosed with BV, the remaining patients were diagnosed with having either intermediate flora (n=42) or dysbacteriosis (n=90). The reported results show that pathogens are associated with BV. This knowledge will further expand our understanding of events leading to BV, which may lead to more effective prevention and treatment strategies.
Significance
The human indigenous microbial communities (microbiota) play critical roles in health and may be especially important for mother and fetus during pregnancy. Using a case-control cohort of 40 women, we characterized weekly variation in the vaginal, gut, and oral microbiota during and after pregnancy. Microbiota membership remained relatively stable at each body site during pregnancy. An altered vaginal microbial community was associated with preterm birth; this finding was corroborated by an analysis of samples from an additional cohort of nine women. We also discovered an abrupt change in the vaginal microbiota at delivery that persisted in some cases for at least 1 y. Our findings suggest that pregnancy outcomes might be predicted by features of the microbiota early in gestation.
ᅟ
The advancement of DNA/RNA, proteins, and metabolite analytical platforms, combined with increased computing technologies, has transformed the field of microbial community analysis. This transformation is evident by the exponential increase in the number of publications describing the composition and structure, and sometimes function, of the microbial communities inhabiting the human body. This rapid evolution of the field has been accompanied by confusion in the vocabulary used to describe different aspects of these communities and their environments. The misuse of terms such as microbiome, microbiota, metabolomic, and metagenome and metagenomics among others has contributed to misunderstanding of many study results by the scientific community and the general public alike. A few review articles have previously defined those terms, but mainly as sidebars, and no clear definitions or use cases have been published. In this editorial, we aim to propose clear definitions of each of these terms, which we would implore scientists in the field to adopt and perfect.
Vaginal atrophy occurring during menopause is closely related to the dramatic decrease in ovarian estrogens due to the loss of follicular activity. Particularly, significant changes occur in the structure of the vaginal mucosa, with consequent impairment of many physiological functions. In this study, carried out on bioptic vaginal mucosa samples from postmenopausal, nonestrogenized women, we present microscopic and ultrastructural modifications of vaginal mucosa following fractional carbon dioxide (CO2) laser treatment. We observed the restoration of the vaginal thick squamous stratified epithelium with a significant storage of glycogen in the epithelial cells and a high degree of glycogen-rich shedding cells at the epithelial surface. Moreover, in the connective tissue constituting the lamina propria, active fibroblasts synthesized new components of the extracellular matrix including collagen and ground substance (extrafibrillar matrix) molecules. Differently from atrophic mucosa, newly-formed papillae of connective tissue indented in the epithelium and typical blood capillaries penetrating inside the papillae, were also observed. Our morphological findings support the effectiveness of fractional CO2 laser application for the restoration of vaginal mucosa structure and related physiological trophism. These findings clearly coupled with striking clinical relief from symptoms suffered by the patients before treatment.
Background
This study was undertaken to determine whether the vaginal microbiota of pregnant women who subsequently had a spontaneous preterm delivery is different from that of women who had a term delivery.
Results
This was a nested case–control study of pregnant women who had a term delivery (controls) and those who had a spontaneous preterm delivery before 34 weeks of gestation (cases). Samples of vaginal fluid were collected longitudinally and stored at −70°C until assayed. A microbial survey using pyrosequencing of V1-V3 regions of 16S rRNA genes was performed. We tested the hypothesis of whether the relative abundance of individual microbial species (phylotypes) was different between women who had a term versus preterm delivery. A suite of bioinformatic and statistical tools, including linear mixed effects models and generalized estimating equations, was used. We show that: 1) the composition of the vaginal microbiota during normal pregnancy changed as a function of gestational age, with an increase in the relative abundance of four Lactobacillus spp., and decreased in anaerobe or strict-anaerobe microbial species as pregnancy progressed; 2) no bacterial taxa differed in relative abundance between women who had a spontaneous preterm delivery and those who delivered at term; and 3) no differences in the frequency of the vaginal community state types (CST I, III, IV-B) between women who delivered at term and those who delivered preterm were detected.
Conclusions
The bacterial taxa composition and abundance of vaginal microbial communities, characterized with 16S rRNA gene sequence-based techniques, were not different in pregnant women who subsequently delivered a preterm neonate versus those who delivered at term.
Objectives:
The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.
Methods:
An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups.
Results:
Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I(2)=33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI -0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years.
Conclusions:
FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated.
Microbial communities associated with agricultural animals are important for animal health, food safety, and public health. Here we combine high-throughput sequencing (HTS), quantitative-PCR assays, and network analysis to profile the poultry-associated microbiome and important pathogens at various stages of commercial poultry production from the farm to the consumer. Analysis of longitudinal data following two flocks from the farm through processing showed a core microbiome containing multiple sequence types most closely related to genera known to be pathogenic for animals and/or humans, including , and . After the final stage of commercial poultry processing, taxonomic richness was ca. 2-4 times lower than the richness of fecal samples from the same flocks and abundance was significantly reduced. Interestingly, however, carcasses sampled at 48 hr after processing harboured the greatest proportion of unique taxa (those not encountered in other samples), significantly more than expected by chance. Among these were anaerobes such as , , , and multiple sequence types. Retail products were dominated by , but also contained 27 other genera, most of which were potentially metabolically active and encountered in on-farm samples. Network analysis was focused on the foodborne pathogen and revealed a majority of sequence types with no significant interactions with other taxa, perhaps explaining the limited efficacy of previous attempts at competitive exclusion of . These data represent the first use of HTS to characterize the poultry microbiome across a series of farm-to-fork samples and demonstrate the utility of HTS in monitoring the food supply chain and identifying sources of potential zoonoses and interactions among taxa in complex communities.
Unlabelled:
Despite its importance to the host, the flower microbiome is poorly understood. We report a culture-independent, community-level assessment of apple flower microbial diversity and dynamics. We collected flowers from six apple trees at five time points, starting before flowers opened and ending at petal fall. We applied streptomycin to half of the trees when flowers opened. Assessment of microbial diversity using tag pyrosequencing of 16S rRNA genes revealed that the apple flower communities were rich and diverse and dominated by members of TM7 and Deinococcus-Thermus, phyla about which relatively little is known. From thousands of taxa, we identified six successional groups with coherent dynamics whose abundances peaked at different times before and after bud opening. We designated the groups Pioneer, Early, Mid, Late, Climax, and Generalist communities. The successional pattern was attributed to a set of prevalent taxa that were persistent and gradually changing in abundance. These taxa had significant associations with other community members, as demonstrated with a cooccurrence network based on local similarity analysis. We also detected a set of less-abundant, transient taxa that contributed to general tree-to-tree variability but not to the successional pattern. Communities on trees sprayed with streptomycin had slightly lower phylogenetic diversity than those on unsprayed trees but did not differ in structure or succession. Our results suggest that changes in apple flower microbial community structure are predictable over the life of the flower, providing a basis for ecological understanding and disease management.
Importance:
Flowering plants (angiosperms) represent a diverse group of an estimated 400,000 species, and their successful cultivation is essential to agriculture. Yet fundamental knowledge of flower-associated microbiotas remains largely unknown. Even less well understood are the changes that flower microbial communities experience through time. Flowers are particularly conducive to comprehensive temporal studies because they are, by nature, ephemeral organs. Here, we present the first culture-independent time series of bacterial and archaeal communities associated with the flowers of apple, an economically important crop. We found unexpected diversity on apple flowers, including a preponderance of taxa affiliated with Deinococcus-Thermus and TM7, phyla that are understudied but thought to be tolerant to an array of environmental stresses. Our results also suggest that changes in microbial community structure on the apple flower may be predictable over the life of the flower, providing the basis for ecological understanding and disease management.
The application of high-throughput sequencing methods has raised doubt in the concept of the uniform healthy vaginal microbiota consisting predominantly of lactobacilli by revealing the existence of more variable bacterial community composition. As this needs to be analyzed more extensively and there is little straightforward data regarding the vaginal mycobiome of asymptomatic women we aimed to define bacterial and fungal communities in vaginal samples from 494 asymptomatic, reproductive-age Estonian women. The composition of the vaginal microbiota was determined by amplifying bacterial 16S rRNA and fungal internal transcribed spacer-1 (ITS-1) regions and subsequently sequencing them using 454 Life Sciences pyrosequencing. We delineated five major bacterial community groups with distinctive diversity and species composition. Lactobacilli were among the most abundant bacteria in all groups, but also members of genus Gardnerella had high relative abundance in some of the groups. Microbial diversity increased with higher vaginal pH values, and was also higher when a malodorous discharge was present, indicating that some of the women who consider themselves healthy may potentially have asymptomatic bacterial vaginosis (BV). Our study is the first of its kind to analyze the mycobiome that colonizes the healthy vaginal environment using barcoded pyrosequencing technology. We observed 196 fungal operational taxonomic units (OTUs), including 16 OTUs of Candida spp., which is more diverse than previously recognized. However, assessing true fungal diversity was complicated because of the problems regarding the possible air-borne contamination and bioinformatics used for identification of fungal taxons as significant proportion of fungal sequences were assigned to unspecified OTUs.
Background:
Bacterial vaginosis is an imbalance of the normal vaginal flora with an overgrowth of anaerobic bacteria and a lack of the normal lactobacillary flora. Women may have symptoms of a characteristic vaginal discharge but are often asymptomatic. Bacterial vaginosis during pregnancy has been associated with poor perinatal outcomes and, in particular, preterm birth (PTB). Identification and treatment may reduce the risk of PTB and its consequences.
Objectives:
To assess the effects of antibiotic treatment of bacterial vaginosis in pregnancy.
Search methods:
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2012), searched cited references from retrieved articles and reviewed abstracts, letters to the editor and editorials.
Selection criteria:
Randomised trials comparing antibiotic treatment with placebo or no treatment, or comparing two or more antibiotic regimens in pregnant women with bacterial vaginosis or intermediate vaginal flora whether symptomatic or asymptomatic and detected through screening.
Data collection and analysis:
Two review authors independently assessed trials for inclusion, trial quality and extracted data. We contacted study authors for additional information.
Main results:
We included 21 trials of good quality, involving 7847 women diagnosed with bacterial vaginosis or intermediate vaginal flora.Antibiotic therapy was shown to be effective at eradicating bacterial vaginosis during pregnancy (average risk ratio (RR) 0.42; 95% confidence interval (CI) 0.31 to 0.56; 10 trials, 4403 women; random-effects, T² = 0.19, I² = 91%). Antibiotic treatment also reduced the risk of late miscarriage (RR 0.20; 95% CI 0.05 to 0.76; two trials, 1270 women, fixed-effect, I² = 0%).Treatment did not reduce the risk of PTB before 37 weeks (average RR 0.88; 95% CI 0.71 to 1.09; 13 trials, 6491 women; random-effects, T² = 0.06, I² = 48%), or the risk of preterm prelabour rupture of membranes (RR 0.74; 95% CI 0.30 to 1.84; two trials, 493 women). It did increase the risk of side-effects sufficient to stop or change treatment (RR 1.66; 95% CI 1.02 to 2.68; four trials, 2323 women, fixed-effect, I² = 0%).In this updated review, treatment before 20 weeks' gestation did not reduce the risk of PTB less than 37 weeks (average RR 0.85; 95% CI 0.62 to 1.17; five trials, 4088 women; random-effects, T² = 0.06, I² = 49%).In women with a previous PTB, treatment did not affect the risk of subsequent PTB (average RR 0.78; 95% CI 0.42 to 1.48; three trials, 421 women; random-effects, T² = 0.19, I² = 72%).In women with abnormal vaginal flora (intermediate flora or bacterial vaginosis), treatment may reduce the risk of PTB before 37 weeks (RR 0.53; 95% CI 0.34 to 0.84; two trials, 894 women).One small trial of 156 women compared metronidazole and clindamycin, both oral and vaginal, with no significant differences seen for any of the pre-specified primary outcomes. Statistically significant differences were seen for the outcomes of prolongation of gestational age (days) (mean difference (MD) 1.00; 95% CI 0.26 to 1.74) and birthweight (grams) (MD 75.18; 95% CI 25.37 to 124.99) however these represent relatively small differences in the clinical setting.Oral antibiotics versus vaginal antibiotics did not reduce the risk of PTB (RR 1.09; 95% CI 0.78 to 1.52; two trials, 264 women). Oral antibiotics had some advantage over vaginal antibiotics (whether metronidazole or clindamycin) with respect to admission to neonatal unit (RR 0.63; 95% CI 0.42 to 0.92, one trial, 156 women), prolongation of gestational age (days) (MD 9.00; 95% CI 8.20 to 9.80; one trial, 156 women) and birthweight (grams) (MD 342.13; 95% CI 293.04 to 391.22; one trial, 156 women).Different frequency of dosing of antibiotics was assessed in one small trial and showed no significant difference for any outcome assessed.
Authors' conclusions:
Antibiotic treatment can eradicate bacterial vaginosis in pregnancy. The overall risk of PTB was not significantly reduced. This review provides little evidence that screening and treating all pregnant women with bacterial vaginosis will prevent PTB and its consequences. When screening criteria were broadened to include women with abnormal flora there was a 47% reduction in preterm birth, however this is limited to two included studies.
Vaginal microbiota form a mutually beneficial relationship with their host and have a major impact on health and disease. In recent years our understanding of vaginal bacterial community composition and structure has significantly broadened as a result of investigators using cultivation-independent methods based on the analysis of 16S ribosomal RNA (rRNA) gene sequences. In asymptomatic, otherwise healthy women, several kinds of vaginal microbiota exist, the majority often dominated by species of Lactobacillus, while others are composed of a diverse array of anaerobic microorganisms. Bacterial vaginosis is the most common vaginal condition and is vaguely characterized as the disruption of the equilibrium of the normal vaginal microbiota. A better understanding of normal and healthy vaginal ecosystems that is based on their true function and not simply on their composition would help better define health and further improve disease diagnostics as well as the development of more personalized regimens to promote health and treat diseases.
The human gastrointestinal tract (GIT) represents one of the most densely populated microbial ecosystems studied to date. Although this microbial consortium has been recognized to have a crucial impact on human health, its precise composition is still subject to intense investigation. Among the GIT microbiota, bifidobacteria represent an important commensal group, being among the first microbial colonizers of the gut. However, the prevalence and diversity of members of the genus Bifidobacterium in the infant intestinal microbiota has not yet been fully characterized, while some inconsistencies exist in literature regarding the abundance of this genus.
In the current report, we assessed the complexity of the infant intestinal bifidobacterial population by analysis of pyrosequencing data of PCR amplicons derived from two hypervariable regions of the 16 S rRNA gene. Eleven faecal samples were collected from healthy infants of different geographical origins (Italy, Spain or Ireland), feeding type (breast milk or formula) and mode of delivery (vaginal or caesarean delivery), while in four cases, faecal samples of corresponding mothers were also analyzed.
In contrast to several previously published culture-independent studies, our analysis revealed a predominance of bifidobacteria in the infant gut as well as a profile of co-occurrence of bifidobacterial species in the infant's intestine.
Recently, ecology has shown a strong interest in network theory. The question, as with any other emerging field, is to what extent we are making real progress in understanding ecological and evolutionary processes or just telling the same stories with fancy new words. I first present a biased overview of the development of network theory, focusing on its search for common patterns across seemingly different systems. I then proceed by discussing some applications of network theory in ecology, namely, species interactions, spatial ecology, epidemiology, and evolution in social groups . Finally, I suggest important contributions of the network approach such as identifying the consequences of heterogeneity for population and community dynamics, potential pitfalls, and future directions.ZusammenfassungIn jüngerer Zeit hat die Ökologie ein starkes Interesse an der Netzwerktheorie gezeigt. Wie bei jedem neu auftauchenden Feld stellt sich die Frage, in welchem Maße wir echte Fortschritte im Verständnis ökologischer und evolutionärer Prozesse machen oder nur dieselben alten Geschichten mit neuen Phantasiebegriffen erzählen. Ich beginne mit einem nicht unparteiischen Überblick über die Entwicklung der Netzwerktheorie, wobei ich mich besonders auf ihre Suche nach den gemeinsamen Mustern von scheinbar unähnlichen Systemen konzentriere. Ich diskutiere dann einige Anwendungen der Netzwerktheorie in der Ökologie, namentlich die Interaktionen zwischen Arten, räumliche Ökologie, Epidemiologie und Evolution in sozialen Gruppen. Schließlich weise ich hin auf bedeutende Beiträge des Netzwerkansatzes, wie die Identifizierung der Folgen von Heterogenität für Populations- und Gemeinschaftsdynamik, auf mögliche Fallstricke und zukünftige Entwicklungsrichtungen.
Discovering a core microbiome is important for understanding the stable, consistent components across complex microbial assemblages. A core is typically defined as the suite of members shared among microbial consortia from similar habitats, and is represented by the overlapping areas of circles in Venn diagrams, in which each circle contains the membership of the sample or habitats being compared. Ecological insight into core microbiomes can be enriched by 'omics approaches that assess gene expression, thereby extending the concept of the core beyond taxonomically defined membership to community function and behaviour. Parameters defined by traditional ecology theory, such as composition, phylogeny, persistence and connectivity, will also create a more complex portrait of the core microbiome and advance understanding of the role of key microorganisms and functions within and across ecosystems.
Here we describe, the longest microbial time-series analyzed to date using high-resolution 16S rRNA tag pyrosequencing of samples taken monthly over 6 years at a temperate marine coastal site off Plymouth, UK. Data treatment effected the estimation of community richness over a 6-year period, whereby 8794 operational taxonomic units (OTUs) were identified using single-linkage preclustering and 21 130 OTUs were identified by denoising the data. The Alphaproteobacteria were the most abundant Class, and the most frequently recorded OTUs were members of the Rickettsiales (SAR 11) and Rhodobacteriales. This near-surface ocean bacterial community showed strong repeatable seasonal patterns, which were defined by winter peaks in diversity across all years. Environmental variables explained far more variation in seasonally predictable bacteria than did data on protists or metazoan biomass. Change in day length alone explains >65% of the variance in community diversity. The results suggested that seasonal changes in environmental variables are more important than trophic interactions. Interestingly, microbial association network analysis showed that correlations in abundance were stronger within bacterial taxa rather than between bacteria and eukaryotes, or between bacteria and environmental variables.
The means by which vaginal microbiomes help prevent urogenital diseases in women and maintain health are poorly understood. To gain insight into this, the vaginal bacterial communities of 396 asymptomatic North American women who represented four ethnic groups (white, black, Hispanic, and Asian) were sampled and the species composition characterized by pyrosequencing of barcoded 16S rRNA genes. The communities clustered into five groups: four were dominated by Lactobacillus iners, L. crispatus, L. gasseri, or L. jensenii, whereas the fifth had lower proportions of lactic acid bacteria and higher proportions of strictly anaerobic organisms, indicating that a potential key ecological function, the production of lactic acid, seems to be conserved in all communities. The proportions of each community group varied among the four ethnic groups, and these differences were statistically significant [χ(2)(10) = 36.8, P < 0.0001]. Moreover, the vaginal pH of women in different ethnic groups also differed and was higher in Hispanic (pH 5.0 ± 0.59) and black (pH 4.7 ± 1.04) women as compared with Asian (pH 4.4 ± 0.59) and white (pH 4.2 ± 0.3) women. Phylotypes with correlated relative abundances were found in all communities, and these patterns were associated with either high or low Nugent scores, which are used as a factor for the diagnosis of bacterial vaginosis. The inherent differences within and between women in different ethnic groups strongly argues for a more refined definition of the kinds of bacterial communities normally found in healthy women and the need to appreciate differences between individuals so they can be taken into account in risk assessment and disease diagnosis.
One challenge facing biologists is to tease out useful information from massive data sets for further analysis. A pathway-based analysis may shed light by projecting candidate genes onto protein functional relationship networks. We are building such a pathway-based analysis system.
We have constructed a protein functional interaction network by extending curated pathways with non-curated sources of information, including protein-protein interactions, gene coexpression, protein domain interaction, Gene Ontology (GO) annotations and text-mined protein interactions, which cover close to 50% of the human proteome. By applying this network to two glioblastoma multiforme (GBM) data sets and projecting cancer candidate genes onto the network, we found that the majority of GBM candidate genes form a cluster and are closer than expected by chance, and the majority of GBM samples have sequence-altered genes in two network modules, one mainly comprising genes whose products are localized in the cytoplasm and plasma membrane, and another comprising gene products in the nucleus. Both modules are highly enriched in known oncogenes, tumor suppressors and genes involved in signal transduction. Similar network patterns were also found in breast, colorectal and pancreatic cancers.
We have built a highly reliable functional interaction network upon expert-curated pathways and applied this network to the analysis of two genome-wide GBM and several other cancer data sets. The network patterns revealed from our results suggest common mechanisms in the cancer biology. Our system should provide a foundation for a network or pathway-based analysis platform for cancer and other diseases.
Little is known about short-term bacterial fluctuations in the human vagina. This study used PCR to assess the variability in concentrations of key vaginal bacteria in healthy women and the immediate response to antibiotic treatment in women with bacterial vaginosis (BV).
Twenty-two women assessed for BV using Amsel's criteria were evaluated daily for 7 or 14 days, then at 2, 3 and 4 weeks, using a panel of 11 bacterium-specific quantitative PCR assays. Participants with BV were treated with 5 days of intravaginal metronidazole. Participants without BV had vaginal biotas dominated by lactobacilli, whose levels fluctuated with menses. With onset of menstruation, quantities of Lactobacillus jensenii and Lactobacillus crispatus decreased and were found to be inversely related to Gardnerella vaginalis concentrations (p<0.001). Women with BV had a variety of fastidious bacteria whose concentrations dropped below detection thresholds 1-5 days after starting metronidazole. Recurrent BV was characterized by initial profound decreases of BV-associated bacteria after treatment followed by subsequent increases at relapse.
The microbiota of the human vagina can be highly dynamic. Healthy women are colonized with Lactobacillus species, but levels can change dramatically over a month. Marked increases in G. vaginalis were observed during menses. Participants with BV have diverse communities of fastidious bacteria that are depleted by vaginal metronidazole therapy. Women with recurrent BV initially respond to antibiotic treatment with steep declines in bacterial concentrations, but these bacteria later reemerge, suggesting that antibiotic resistance in these bacteria is not an important factor mediating BV recurrence.
In healthy humans, many microbial consortia constitute rich ecosystems with dozens to hundreds of species, finely tuned to functions relevant to human health. Medical interventions, lifestyle changes, and the normal rhythms of life sometimes upset the balance in microbial ecosystems, facilitating pathogen invasions or causing other clinically relevant problems. Some diseases, such as bacterial vaginosis, have exactly this sort of community etiology. Mathematical network theory is ideal for studying the ecological networks of interacting species that comprise the human microbiome. Theoretical networks require little consortia specific data to provide insight into both normal and disturbed microbial community functions, but it is easy to incorporate additional empirical data as it becomes available. We argue that understanding some diseases, such as bacterial vaginosis, requires a shift of focus from individual bacteria to (mathematical) networks of interacting populations, and that known emergent properties of these networks will provide insights that would be otherwise elusive.
Recent developments in the quantitative analysis of complex networks, based largely on graph theory, have been rapidly translated to studies of brain network organization. The brain's structural and functional systems have features of complex networks--such as small-world topology, highly connected hubs and modularity--both at the whole-brain scale of human neuroimaging and at a cellular scale in non-human animals. In this article, we review studies investigating complex brain networks in diverse experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans) and provide an accessible introduction to the basic principles of graph theory. We also highlight some of the technical challenges and key questions to be addressed by future developments in this rapidly moving field.
To assess associations of nonulcerative sexually transmitted diseases (STDs) with human immunodeficiency virus (HIV)-susceptible
leukocytes on female genital mucosa, cervicovaginal specimens from 32 HIV-negative STD clinic patients with gonorrhea, chlamydial
infection, or trichomoniasis were compared with specimens from 32 clinic patients without these infections. Twenty-eight patients
had single infections (15 gonorrhea, 10 chlamydial infection, 3 trichomoniasis), and 4 had dual infections. A saline vaginal
wash and saline suspensions of vaginal wall scrapings, ectocervical scrapings, and endocervical brushings were analyzed by
flow cytometry. Specimens from the endocervix had the highest proportions of lymphocytes, monocytes, and Langerhans' cells.
The median number of endocervical CD4 lymphocytes/10,000 cells was greater among patients with STDs than among those without
(476 vs. 245; P < .001). These data suggest that the endocervix may have a particularly important role in heterosexual HIV transmission and
that nonulcerative STDs may facilitate HIV transmission by increasing the presence of CD4 lymphocytes at this site.
Cross-sectional studies suggest an association between bacterial vaginosis (BV) and HIV-1 infection. However, an assessment of a temporal effect was not possible.
To determine the association of BV and other disturbances of vaginal flora with HIV seroconversion among pregnant and postnatal women in Malawi, Africa.
Longitudinal follow-up of pregnant and postpartum women.
Women attending their first antenatal care visit were screened for HIV after counselling and obtaining informed consent. HIV-seronegative women were enrolled and followed during pregnancy and after delivery. These women were again tested for HIV at delivery and at 6-monthly visits postnatally. Clinical examinations and collection of laboratory specimens (for BV and sexually transmitted diseases) were conducted at screening and at the postnatal 6-monthly visits. The diagnosis of BV was based on clinical criteria. Associations of BV and other risk factors with HIV seroconversion, were examined using contingency tables and multiple logistic regression analyses on antenatal data, and Kaplan-Meier proportional hazards analyses on postnatal data.
Among 1196 HIV-seronegative women who were followed antenatally for a median of 3.4 months, 27 women seroconverted by time of delivery. Postnatally, 97 seroconversions occurred among 1169 seronegative women who were followed for a median of 2.5 years. Bacterial vaginosis was significantly associated with antenatal HIV seroconversion (adjusted odds ratio = 3.7) and postnatal HIV seroconversion (adjusted rate ratio = 2.3). There was a significant trend of increased risk of HIV seroconversion with increasing severity of vaginal disturbance among both antenatal and postnatal women. The approximate attributable risk of BV alone was 23% for antenatal HIV seroconversions and 14% for postnatal seroconversions.
This prospective study suggests that progressively greater disturbances of vaginal flora, increase HIV acquisition during pregnancy and postnatally. The screening and treating of women with BV could restore normal flora and reduce their susceptibility to HIV.
Objective:
The vaginal microbiota helps protect the female genital tract from disease. We sought to describe the composition of the vaginal microbiota in premenopausal, perimenopausal, and postmenopausal women and to explore the association between the microbiota and vulvovaginal atrophy (VVA).
Methods:
Eighty-seven women (aged 35-60 y) were classified as premenopausal (n = 30), perimenopausal (n = 29), or postmenopausal (n = 28) according to Stages of Reproductive Aging Workshop guidelines. Midvaginal bacterial community composition was characterized by 16S ribosomal RNA gene analysis.
Results:
Bacterial communities clustered into six community state types (CSTs), of which four were dominated by Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, or Lactobacillus jensenii, and two (CST IV-A and CST IV-B) had low relative abundance of Lactobacillus. CST IV-A was characterized by Streptococcus and Prevotella, whereas CST IV-B was characterized by Atopobium. There were significant associations between menopause stage and CST (P = 0.004) and between VVA and CST (P = 0.002). Perimenopausal women were more likely to be classified as CST IV-A or L. gasseri CST, whereas postmenopausal women were often classified as CST IV-A. CSTs dominated by L. crispatus and L. iners were more prevalent in premenopausal women. Nineteen participants had signs of mild or moderate VVA. Compared with women with no VVA, the vaginal microbiota of women with mild or moderate atrophy had 25-fold greater odds of being classified as CST IV-A versus L. crispatus CST (adjusted odds ratio, 25.89; 95% credible interval, 2.98-406.79).
Conclusions:
A distinct bacterial community state (CST IV-A) with a low relative abundance of Lactobacillus is associated with VVA. Future studies recruiting a larger number of women are needed to replicate the findings. This study provides an impetus for future longitudinal studies designed to manage, modulate, and restore vaginal microbiota homeostasis, which would provide stronger evidence for a causal relationship with VVA and ultimately improve the treatment and prevention of atrophic vaginitis in menopause.
Skin microorganisms have adapted to utilize the sparse nutrients available on the skin
Many cutaneous microorganisms can produce molecules that inhibit the colonization of other microorganisms or alter their behaviour
The skin microbiota of a healthy adult remains stable over time, despite environmental perturbations
Shotgun metagenomics provides greater resolution than traditional amplicon sequencing, enabling surveys of the skin microbiota at the kingdom, species, strain or gene level
Skin microorganisms have important roles in educating the innate and adaptive arms of the cutaneous immune system
Some skin diseases are associated with an altered microbial state; reversion of this dysbiosis may help prevent and/or treat the disease
The composition of the intestinal microbiota varies among individuals and throughout development, and is dependent on host and environmental factors. However, although the microbiota is constantly exposed to environmental challenges, its composition and function in an individual are stable against perturbations, as microbial communities are resilient and resistant to change. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and also between the microorganisms and the intestinal interface of the host. The resilience of the healthy microbiota protects us from dysbiosis-related diseases, such as inflammatory bowel disease (IBD) or metabolic disorder. By contrast, a resilient dysbiotic microbiota may cause disease. In this Opinion article, we propose that microbial resilience has a key role in health and disease. We will discuss the concepts and mechanisms of microbial resilience against dietary, antibiotic or bacteriotherapy-induced perturbations and the implications for human health.
Objectives: To assess the effect of microablative fractional CO2 laser (MFCO2-Laser) therapy on the vaginal microenvironment of postmenopausal women.
Methods: Three laser therapies at monthly intervals were applied in postmenopausal women with moderate to severe symptoms of genitourinary syndrome of menopause, pH of vaginal fluid >4.5 and superficial epithelial cells on vaginal smear <5%. Vaginal fluid pH values, fresh wet mount microscopy, Gram stain and aerobic and anaerobic cultures were evaluated at baseline and 1 month after each subsequent therapy. Nugent score and Hay-Ison criteria were used to evaluate vaginal flora.
Results: Fifty-three women (mean age 57.2 ± 5.4 years) participated and completed this study. MFCO2-Laser therapy increased Lactobacillus (p < 0.001) and normal flora (p < 0.001) after the completion of the therapeutic protocol, which decreased vaginal pH from a mean of 5.5 ± 0.8 (initial value) to 4.7 ± 0.5 (p < 0.001). The prevalence of Lactobacillus changed from 30% initially to 79% after the last treatment. Clinical signs and symptoms of bacterial vaginosis, aerobic vaginitis or candidiasis did not appear in any participant.
Conclusion: MFCO2-Laser therapy is a promising treatment for improving the vaginal health of postmenopausal women by helping repopulate the vagina with normally existing Lactobacillus species and reconstituting the normal flora to premenopausal status.
Background:
Preterm delivery is a leading cause of neonatal morbidity and death. It often results from chorioamnionitis, which is a complication of bacterial vaginosis. Probiotics are effective in the treatment of bacterial vaginosis in women who were not pregnant; studies in pregnant woman are missing.
Objective:
The purpose of this study was to evaluate whether an oral probiotic food supplement supports the maintenance or restoration of a normal vaginal microbiota during pregnancy.
Study design:
We conducted a randomized, placebo-controlled, triple-blind, parallel group trial. Oral Lactobacillus rhamnosus GR-1and L reuteri RC-14 (10(9) colony-forming units) or placebo were administered for 8 weeks to women with <12 completed weeks of pregnancy. Participants were enrolled at Tuebingen University Hospital and 10 recruiting gynecologic practices. Vaginal swabs were taken before and after intervention and analyzed according to the Nugent scoring system. Telephone interviews were performed before and after intervention and after delivery. Primary outcome was the proportion of swabs with normal Nugent score (<4) after intervention, compared by Fisher's exact test in an intention-to-treat analysis.
Results:
Three hundred twenty pregnant women were enrolled. Vaginal swabs were analyzed from 290 women before and 271 women after intervention. The proportion of normal vaginal microbiota decreased from 82.6-77.8% in the treatment group and from 79.1-74.3% in the placebo group, with no significant difference across groups after intervention (P=.297).
Conclusion:
Oral probiotics may be suitable for implementation in antenatal care but, as administered here, had no effect on vaginal health during mid gestation. Other application routes or probiotic preparations may be more effective in supporting vaginal microbiota during pregnancy.
Bacterial vaginosis (BV) is one of the most common causes of vaginal symptoms in US women, but its causal mechanism has not
yet been defined. BV is more prevalent in women who are immunosuppressed, and several risk factors for the development of
BV are associated with lower quantities of immune mediators in vaginal fluid. In contrast, the poor reproductive health outcomes
associated with BV, such as preterm birth and HIV-1 acquisition, are associated with increased levels of pro-inflammatory
immune mediators in the genital tract. In this manuscript we discuss how variations in the host immune profile and environmental
effects on host immunity may impact risk for BV, as well as the risk of complications associated with BV.
These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 30-May 2, 2013. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2010 (MMWR Recomm Rep 2010;59 [No. RR-12]). These updated guidelines discuss 1) alternative treatment regimens for Neisseria gonorrhoeae; 2) the use of nucleic acid amplification tests for the diagnosis of trichomoniasis; 3) alternative treatment options for genital warts; 4) the role of Mycoplasma genitalium in urethritis/cervicitis and treatment-related implications; 5) updated HPV vaccine recommendations and counseling messages; 6) the management of persons who are transgender; 7) annual testing for hepatitis C in persons with HIV infection; 8) updated recommendations for diagnostic evaluation of urethritis; and 9) retesting to detect repeat infection. Physicians and other health-care providers can use these guidelines to assist in the prevention and treatment of STDs.
Bacterial vaginosis (BV) is a common cause of vaginal discharge in reproductive age women around the world and is associated with several poor reproductive health outcomes, including HIV-1 acquisition. One possible mechanism for this association is the inflammatory immune response induced by BV in the cervical and vaginal mucosae. There is significant heterogeneity in reports of markers of cervicovaginal inflammation in women with BV, likely due to microbial and host diversity, as well as differences in study design. In this article, we review the characteristics of the mucosal immune response in BV, the potential role of lactobacilli in modulating that response, and the impact of individual BV-associated bacterial species on mucosal immunity. We focus on inflammatory markers that are proposed to increase the risk of HIV-1 acquisition.
Given the known dysbiosis of gut microflora in inflammatory bowel disease, there has been great enthusiasm about the potential for fecal microbiota transplantation (FMT) as a treatment. This editorial accompanies a prospective series of five patients with ulcerative colitis who underwent FMT, but did not achieve remission. I discuss the important observations from this study and point out that the lack of clinical efficacy and observed side effects warrant caution in the ongoing pursuit of this treatment option.
Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time - especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.
Metagenomics and 16S pyrosequencing have enabled the study of ecosystem structure and dynamics to great depth and accuracy. Co-occurrence and correlation patterns found in these data sets are increasingly used for the prediction of species interactions in environments ranging from the oceans to the human microbiome. In addition, parallelized co-culture assays and combinatorial labelling experiments allow high-throughput discovery of cooperative and competitive relationships between species. In this Review, we describe how these techniques are opening the way towards global ecosystem network prediction and the development of ecosystem-wide dynamic models.
The various microbiota normally associated with the human body have an important influence on human development, physiology, immunity, and nutrition. This is certainly true for the vagina wherein communities of mutualistic bacteria constitute the first line of defense for the host by excluding invasive, nonindigenous organisms that may cause disease. In recent years much has been learned about the bacterial species composition of these communities and how they differ between individuals of different ages and ethnicities. A deeper understanding of their origins and the interrelationships of constituent species is needed to understand how and why they change over time or in response to changes in the host environment. Moreover, there are few unifying theories to explain the ecological dynamics of vaginal ecosystems as they respond to disturbances caused by menses and human activities such as intercourse, douching, and other habits and practices. This fundamental knowledge is needed to diagnose and assess risk to disease. Here we summarize what is known about the species composition, structure, and function of bacterial communities in the human vagina and the applicability of ecological models of community structure and function to understanding the dynamics of this and other ecosystems that comprise the human microbiome.
Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.
To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male-to-female HIV transmission.
Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open-label no gel arm.
Study participants from Malawi, South Africa, Zambia, Zimbabwe, and the USA were instructed to apply study gel up to 1 h before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up.
The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 gel, BufferGel, placebo gel, and no gel arms were 2.70, 4.14, 3.91, and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 gel arm was lower than the placebo gel arm (hazard ratio = 0.7, P = 0.10) and the no gel arm (hazard ratio = 0.67, P = 0.06). HIV incidence rates were similar in the BufferGel and both placebo gel (hazard ratio = 1.10, P = 0.63) and no gel control arms (hazard ratio = 1.05, P = 0.78). HIV incidence was similar in the placebo gel and no gel arms (hazard ratio = 0.97, P = 0.89).
The 0.5% PRO2000 gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the Microbicide Development Programme (MDP) 301 trial have confirmed that 0.5% PRO2000 gel has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were well tolerated.
Please cite this paper as: Lamont R, Sobel J, Akins R, Hassan S, Chaiworapongsa T, Kusanovic J, Romero R. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG 2011;118:533–549.
Vaginal microbiome studies provide information that may change the way we define vaginal flora. Normal flora appears dominated by one or two species of Lactobacillus. Significant numbers of healthy women lack appreciable numbers of vaginal lactobacilli. Bacterial vaginosis (BV) is not a single entity, but instead consists of different bacterial communities or profiles of greater microbial diversity than is evident from cultivation-dependent studies. BV should be considered a syndrome of variable composition that results in different symptoms, phenotypical outcomes, and responses to different antibiotic regimens. This information may help to elucidate the link between BV and infection-related adverse outcomes of pregnancy.
To determine whether different racial groups shared common types of vaginal microbiota, we characterized the composition and structure of vaginal bacterial communities in asymptomatic and apparently healthy Japanese women in Tokyo, Japan, and compared them with those of White and Black women from North America. The composition of vaginal communities was compared based on community profiles of terminal restriction fragments of 16S rRNA genes and phylogenetic analysis of cloned 16S rRNA gene sequences of the numerically dominant bacterial populations. The types of vaginal communities found in Japanese women were similar to those of Black and White women. As with White and Black women, most vaginal communities were dominated by lactobacilli, and only four species of Lactobacillus (Lactobacillus iners, Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus gasseri) were commonly found. Communities dominated by multiple species of lactobacilli were common in Japanese and White women, but rare in Black women. The incidence, in Japanese women, of vaginal communities with several non-Lactobacillus species at moderately high frequencies was intermediate between Black women and White women. The limited number of community types found among women in different ethnic groups suggests that host genetic factors, including the innate and adaptive immune systems, may be more important in determining the species composition of vaginal bacterial communities than are cultural and behavioral differences.
To determine the risk factors for CD4+ lymphocyte counts of 200 cells/mm(3) or lower in HIV-positive pregnant women in Nigeria.
A cross-sectional data analysis from a prospective cohort of 515 HIV-positive women attending a prenatal clinic. Risk of a low CD4+ count was estimated using logistic regression analysis.
CD4+ lymphocyte counts of 200 cells/mm(3) or lower (280+/-182 cells/mm(3)) were recorded in 187 (36.3%) out of 515 HIV-positive pregnant women included in the study. Low CD4+ count was associated with older age (adjusted odds ratio [aOR] 10.71; 95% confidence interval [CI], 1.20-95.53), lack of condom use (aOR, 5.16; 95% CI, 1.12-23.8), history of genital ulcers (aOR, 1.78; 95% CI, 1.12-2.82), and history of vaginal discharge (aOR; 1.62; 1.06-2.48).
Over 35% of the HIV-positive pregnant women had low CD4+ counts, indicating the need for treatment. The findings underscore the need to integrate prevention of mother-to-child transmission with HIV treatment and care, particularly services for sexually transmitted infections.
A randomised trial was done to evaluate the impact of improved sexually transmitted disease (STD) case management at primary health care level on the incidence of HIV infection in the rural Mwanza region of Tanzania. HIV incidence was compared in six intervention communities and six pair-matched comparison communities. A random cohort of about 1000 adults aged 15-54 years from each community was surveyed at baseline and at follow-up 2 years later. Intervention consisted of establishment of an STD reference clinic, staff training, regular supply of drugs, regular supervisory visits to health facilities, and health education about STDs. 12,537 individuals were recruited. Baseline HIV prevalences were 3.8% and 4.4% in the intervention and comparison communities, respectively. At follow-up, 8845 (71%) of the cohort were seen. Of those initially seronegative, the proportions seroconverting over 2 years were 48 of 4149 (1.2%) in the intervention communities and 82 of 4400 (1.9%) in the comparison communities. HIV incidence was consistently lower in the intervention communities in all six matched pairs. Allowing for the community-randomised design and the effects of confounding factors, the estimated risk ratio was 0.58 (95% CI 0.42-0.79, p = 0.007). No change in reported sexual behaviour was observed in either group. We conclude that improved STD treatment reduced HIV incidence by about 40% in this rural population. This is the first randomised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population.
As various drugs might have an effect on the fetus during pregnancy, the use of drugs should be minimized in the pregnant woman. Since bacterial vaginosis (BV) can be associated with prematurity and postpartum complications, we searched for alternative therapy for its cure during pregnancy. Commercial yoghurt incorporates both factors necessary for maintaining the protective mechanism of the vagina, vaginal pH and lactobacillus. A total of 32 women with BV in the first trimester of pregnancy were treated with intravaginal application of yoghurt. The result was favorable indicating that the continuous correction of vaginal pH and lactobacillus flora is crucial for normal vaginal ecology. During pregnancy, a local treatment restoring the normal acidity and vaginal flora, without systemic effect, may be preferable to any other treatment.
The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities.
This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios.
The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses.
We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors.