A comprehensive knowledge of the vaginal ecosystem is critical for the development of successful approaches to the treatment of infections. The role of Lactobacilli in preventing vulvovaginal candidiasis (VVC) is controversial. In this study, we investigated the therapeutic effects and mechanism of Lactobacillus crispatus or delbrueckii on vaginitis caused by Candida albicans in a Sprague–Dawley rat model. A microbiological evaluation was performed by Gram staining and fungal colonies were enumerated. The antifungal efficacy of the two Lactobacillus strains was assessed by hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), immunohistochemical detection of interferon-γ (IFN-γ), interleukin (IL)-4, IL-17, and epithelial-derived IgG (RP125). Our in vitro results showed that the inhibitory activity against Candida colony-forming unit (CFU) counts was demonstrated by the two Lactobacillus strains (P < 0.001). Our results indicated that Lactobacillus administration played an indispensable role in maintaining the immune homeostasis, and decreasing the Th1/Th2 ratio (IFN-γ/IL-4) by regulating the epithelial secretion of cytokines that inhibit epithelial proinflammatory cytokine release, while increasing epithelial-derived IgG expression (P < 0.05), suggesting antibody-mediated protection. Our results implicate L. crispatus and L. delbrueckii as a potential adjunct biotherapeutic agent in women with VVC, especially for those with drug resistance, adverse effects or contraindications when using antifungal agents. Further large, long-term, well-planned clinical studies should be performed in clinical practice to determine their clinical potential of L. crispatus and L. delbrueckii as an adjunct treatment for VVC.

Background: High-risk human papilloma virus (hrHPV) is the main causal factor of cervical precancer and cancer when persistent infection is left untreated. Previous studies have confirmed the vaginal microbiota is associated with HPV infection and the development of cervical lesions. The microbiota at different parts of the female genital tract is closely related but different from each other. To analyze the distinction between the vaginal and cervical microbiota of hrHPV(+) women in China, one hundred subjects were recruited, including 10 patients with HPV16/18(+) and cervical carcinoma, 38 patients with HPV16/18(+) but no cervical carcinoma, 32 patients with other hrHPV(+) and 20 healthy controls with HPV(−). Vaginal and cervical microbiota were separately tested through next-generation sequencing (NGS) targeting the variable region (V3-V4) of the bacterial ribosome 16S rRNA gene. Results: HrHPV(+) subjects had higher percentages of vaginal douching history (P = 0.001), showed more frequent usage of sanitary pads (P = 0.007), had more sex partners (P = 0.047), were more sexually active (P = 0.025) and more diversed in ways of contraception (P = 0.001). The alpha diversity of the cervical microbiota was higher than that of the vagina. The cervical microbiota consisted of a lower percentage of Firmicutes and a higher percentage of Proteobacteria than the vagina at the phylum level. Sphingomonas, belonging to α-Proteobacteria, was almost below the detection limit in the vagina but accounted for five to 10 % of the bacteria in the hrHPV(−) cervix (P<0.001) and was inversely associated with hrHPV infection (P<0.05). Pseudomonas, belonging to γ-Proteobacteria, could hardly be seen in the normal vagina and shared a small percentage in the normal cervix but was significantly higher in the HPV16/18(+) (P<0.001) and cancerous cervix (P<0.05). No significant difference was shown in the percentage of BV associated anaerobes, like Gardnerella, Prevotella, Atopobium and Sneathia, between the cevix and vigina. Conclusions: The proportion of Proteobacteria was significantly higher in the cervical microbiota than that of vagina. The hrHPV infection and cervical cancer was positively associated with Pseudomonas and negatively associated with Sphingomonas. It is of great improtance to deeply explore the cervical microbiota and its function in cervical cacinogenesis.

Background. Bacterial vaginosis (BV), one of the most common vaginal ecosystem-related microbiologic syndromes, is the most common disorder in women of reproductive age. Gardnerella (G.) vaginalis is the predominant species causing this infection. Our aim was to compare the antimicrobial susceptibilities of metronidazole and clindamycin against G. vaginalis at planktonic and biofilm levels. Methods. From September 2019 to October 2019, we recruited a total of 10 patients with BV who underwent gynecological examinations at Beijing Obstetrics and Gynecology Hospital. G. vaginalis isolates were obtained from the vagina and identified using their characteristic colony morphology. Sequence data of clinical G. vaginalis isolates were confirmed by comparing 16S rDNA sequences. Subsequently, clinical isolates were evaluated for antimicrobial susceptibilities in vitro to metronidazole and clindamycin at planktonic and biofilm levels. The minimum inhibitory concentration (MIC) for metronidazole and clindamycin was evaluated by antimicrobial susceptibility testing. The minimum biofilm eradication concentration (MBEC) was evaluated by the biofilm inhibition assay. Results. Planktonic clinical isolates showed a significantly higher susceptibility rate (76.67%) and lower resistance rate (23.33%) to clindamycin than to metronidazole (susceptibility rate: 38.24%; resistance rate: 58.82%; P<0.05 for both). Furthermore, in comparison to planktonic isolates, the minimum inhibitory concentration (MIC) of metronidazole was significantly higher for biofilm-forming isolates (7.3 ± 2.6 μg/mL vs. 72.4 ± 18.3 μg/mL; P=0.005); the resistance rate was 27.3%, and the minimum biofilm eradication concentration (MBEC) was >128 μg/mL. Moreover, the MIC of clindamycin was higher too for biofilm-forming isolates (0.099 ± 0.041 μg/mL vs. 23.7 ± 9.49 μg/mL; P=0.034); the resistance rate was 27.3%, and the MBEC of clindamycin was 28.4 ± 6.50 μg/mL. Conclusion. Our results indicate that in comparison to metronidazole, clindamycin seems to be a better choice to tackle G. vaginalis as it exhibits a relatively higher susceptibility rate and lower resistance rate.

Vulvovaginal candidiasis (VVC) is a common infectious disease of the lower genital tract. Nystatin, a polyene fungicidal antibiotic, is used as a topical antifungal agent for VVC treatment. The aim of the current study was to investigate the possible immunomodulatory effects of nystatin on the vaginal mucosal immune response during Candida albicans infection and examine its role in protection of vaginal epithelial cell (VEC) ultrastructure. Following infection with C. albicans, IFN-γ and IL-17 levels in VECs were significantly elevated, while the presence of IgG was markedly decreased as compared to uninfected controls (P < 0.05). No significant differences in IL4 expression were observed. After treatment with nystatin, the level of IFN-γ, IL-17 and IgG was dramatically increased in comparison to the untreated group (P < 0.05). Transmission electron microscopy revealed that C. albicans invades the vaginal epithelium by both induced endocytosis and active penetration. Nystatin treatment protects the ultrastructure of the vaginal epithelium. Compared with the untreated C. albicans-infected group, Flameng scores which measure mitochondrial damage of VECs were markedly decreased (P < 0.001) and the number of adhesive and invasive C. albicans was significantly reduced (P < 0.01) after treatment with nystatin. Nystatin plays a protective role in the host defense against C. albicans by up-regulating the IFN-γ-related cellular response, the IL-17 signaling pathway and possibly through enhancing VEC-derived IgG-mediated immunity. Furthermore, nystatin notably improves the ultramorphology of the vaginal mucosa, partially through the protection of mitochondria ultrastructure in VECs and inhibition of adhesion and invasion by C. albicans. Together, these effects enhance the immune response of the vaginal mucosa against C. albicans and protect the ultrastructure of vaginal epithelium in VVC rats.

The Vaginal Microecology Evaluation System (VMES) is a technical and economically feasible tool to assess the vaginal microbiomes of gynecological outpatients. The aim of this review was to introduce knowledge on the potential changes that can occur in the vaginal microbiome and how to use the Evaluation System to diagnose and manage a broad range of vaginal infections. This review was based on data in articles published in PubMed up to December 10, 2018, with the following keywords: “Vaginal microecosystem”, “vaginal microbiome”, “vaginal microbiota”, and “vaginal flora”. Original articles and critical reviews on VMES and vaginal microbiota selected for this review. References of the retrieved articles were also screened to search for potentially relevant papers. Any imbalance in the naturally occurring vaginal bacterial flora may result in infections such as bacterial vaginitis, aerobic vaginitis, vulvovaginal candidiasis, or Trichomonas vaginalis. VMES is mainly composed of morphological and functional microecological indicators. The former diagnostic modality includes bacterial density, flora diversity, dominant bacterial flora, indicators of inflammation, pathogenic microorganisms, Nugent score, and AV score. Functional indicators consist of two main components: metabolites and microbial enzymes. The establishment of VMES has a high clinical value in the treatment of vaginal infections. It opens up new opportunities for the comprehensive management of dysbacteriosis when such infections occur. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

Vulvovaginal candidiasis (VVC) is an opportunistic fungal infection predominantly caused by Candida albicans affecting a significant number of women of reproductive age. The Chinese medicine, the Baofukang suppository is widely used in the clinic for its antimicrobial activity and is therefore of great interest as a potential antifungal drug for the prevention of VVC. We evaluated the cytotoxic activity of the Baofukang suppository using the VK2/E6E7 vaginal epithelial cell (VEC) line. When treated with the Baofukang suppository, all of the immunocompetent cytokines and chemokines (e.g., IL-2, IL-4, IL-6, IL-8, and IL-17) by infected VK2/E6E7 cells was statistically up-regulated (P < 0.05), except IL-4 (11.70 ± 1.82 vs. 14.88 ± 4.72, P = 0.343) compared to the infected control cells. The secretion of non-B IgG also exhibited the same trend. Our scanning electron microscopy results revealed that C. albicans can invade VECs by both induced endocytosis and active penetration. The Baofukang suppository could effectively inhibit the adhesion, hyphal formation, and proliferation, as well as notably restore the vaginal epithelial cell morphology, viability, and enhance the local immune function of the VECs. These preliminary results suggest promising antimicrobial properties of the Baofukang suppository, which may be efficacious as an antifungal therapy candidate via up-regulating Th1 cellular immunity, the Th17-axis of the innate immune response, and the secretion of vaginal epithelial-derived IgG. These combined effects collectively restore the immune function of the infected VECs against C. albicans in vitro.