Alternations in the human skin, gut and vaginal microbiomes in perimenopausal or postmenopausal Vulvar lichen sclerosus.

Vulvar lichen sclerosus (VLS) is a chronic and progressive dermatologic condition that can cause physical dysfunction, disfigurement, and impaired quality of life. However, the etiology of VLS remains unknown. The vulvar skin, intestinal and vaginal microbiomes have been postulated to play important roles in the pathogenesis of this disease. The aim of this study was to compare the compositional characteristics of the vulvar skin, vagina, and gut microbiota between perimenopausal or postmenopausal VLS patients and healthy controls. The study involved six perimenopausal or postmenopausal VLS patients which were based on characteristic clinical manifestations and histologic confirmation and five healthy controls. The pruritus severity of each patient was evaluated using the NRS scale, and the dermatology-specific health-related quality of life was assessed using the Skindex-16. Metagenomic sequencing was performed, and the results were analyzed for alpha and beta diversity. LEfSe analysis were used to investigate the microbial alterations in vulvar skin, gut and vagina. KEGG databases were used to analyze differences in functional abundance. The study found significant differences in alpha diversity between the two groups in stool and vaginal samples (P < 0.05). Patients with VLS had a higher abundance of Enterobacter cloacae, Flavobacterium_branchiophilum, Mediterranea_sp._An20, Parabacteroides_johnsoniiand Streptococcus_bovimastitidis on the vulvar skin, while Corynebacterium_sp._zg-913 was less abundant compared to the control group. The relative abundance of Sphingomonas_sp._SCN_67_18, Sphingobium_sp._Ant17, and Pontibacter_sp_BT213 was significantly higher in the gut samples of patients with VLS.Paenibacillus_popilliae,Gemella_asaccharolytica, and Coriobacteriales_bacterium_DNF00809 compared to the control group. Additionally, the vaginal samples of patients with VLS exhibited a significantly lower relative abundance of Bacteroidales_bacterium_43_8, Bacteroides_sp._CAG:20, Blautia_sp._AM28-10, Fibrobacter_sp._UWB16, Lachnospiraceae_bacterium_AM25-39, Holdemania_filiformis, Lachnospiraceae_bacterium_GAM79, and Tolumonas_sp. Additionally, the butyrate-producing bacterium SS3/4 showed a significant difference compared to the controls. The study found a negative relationship between Sphingobium_sp._Ant17 in stool and Skindex-16 (P < 0.05), while Mediterranea_sp._An20 had a positive correlation with Skindex-16 (P < 0.05) in the skin. Additionally, our functional analysis revealed alterations in Aminoacyl_tRNA_biosynthesis, Glutathione_metabolism, the pentose phosphate pathway, and Alanine__aspartate_and_glutamate_metabolism in the VLS patient group. The study suggests that perimenopausal or postmenopausal patients with VLS have a modified microbiome in the vulvar skin, gut, and vagina. This modification is linked to abnormal energy metabolism, increased oxidative stress, and abnormal amino acid metabolism.

Vaginal and tumor microbiomes in gynecological cancer (Review).

Cervical, ovarian and endometrial cancer are the three most common types of gynecologic cancer. As a hub, the vagina connects the site of gynecological cancer with the external environment. Lactobacilli participate in the formation of a healthy vaginal microenvironment as the first line of defense against pathogen invasion; a dysbiotic vaginal microenvironment loses its original protective function and is associated with the onset, metastasis, poor efficacy and poor prognosis of gynecological cancer. The early diagnosis of cancer is the key to improve the survival time of patients with cancer. The screening of Porphyromonas, Sneathia and Atopobium vaginae, and other microbial markers, can assist the diagnosis of gynecological cancer, and screen out the high-risk population as early as possible. With the in-depth study of the microbes in tumor tissues, reasearchers have analyzed the immunological associations of microorganisms in tumor tissues. Due to the structural-functional interconnection between the organ of gynecological tumorigenesis and the vagina, the present study aims to review the relationship between vaginal and tumor microorganisms and gynecological cancer in terms of occurrence, screening, treatment and prognosis.

Altered Innate Immunity and Damaged Epithelial Integrity in Vaginal Microbial Dysbiosis.

The role of neutrophils relative to vaginal dysbiosis is unclear. We hypothesize that bacterial vaginosis (BV)-associated bacteria may induce the activation and accumulation of mucosal neutrophils within the female reproductive tract (FRT), resulting in epithelial barrier damage. We collected endocervical cytobrushes from women with and without BV and assessed bacteria community type and frequency/functional phenotypes of neutrophils. We performed in vitro whole blood co-cultures with BV-associated bacteria and healthy vaginal commensals and assessed their impact on epithelial integrity using transepithelial electrical resistance. We demonstrated increased neutrophil frequency (p < 0.0001), activation (p < 0.0001), and prolonged lifespan (p < 0.0001) in the cytobrushes from women with non-Lactobacillus dominant (nLD) communities. Our in vitro co-cultures confirmed these results and identified significant barrier damage in the presence of neutrophils and G. vaginalis. Here, we demonstrate that BV-associated bacteria induce neutrophil activation and increase lifespan, potentially causing accumulation in the FRT and epithelial barrier damage.

Complete Genome of Lactobacillus iners KY Using Flongle Provides Insight Into the Genetic Background of Optimal Adaption to Vaginal Econiche.

Despite the importance of Lactobacillus iners and its unique characteristics for the study of vaginal adaption, its genome and genomic researches for identifying molecular backgrounds of these specific phenotypes are still limited. In this study, the first complete genome of L. iners was constructed using a cost-effective long-read sequencing platform, Flongle from Oxford Nanopore, and comparative genome analysis was conducted using a total of 1,046 strain genomes from 10 vaginal Lactobacillus species. Single-molecule sequencing using Flongle effectively resolved the limitation of the 2nd generation sequencing technologies in dealing with genomic regions of high GC contents, and comparative genome analysis identified three potential core genes (INY, ZnuA, and hsdR) of L. iners which was related to its specific adaption to the vaginal environment. In addition, we performed comparative prophage analysis for 1,046 strain genomes to further identify the species specificity. The number of prophages in L. iners genomes was significantly smaller than other vaginal Lactobacillus species, and one of the specific genes (hsdR) was suggested as the means for defense against bacteriophage. The first complete genome of L. iners and the three specific genes identified in this study will provide useful resources to further expand our knowledge of L. iners and its specific adaption to the vaginal econiche.

Study on the correlation among dysbacteriosis, imbalance of cytokine and the formation of intrauterine adhesion.

BACKGROUND: Intrauterine adhesion (IUA) is one of the most important causes of female infertility, while iatrogenic endometrial injury is the main, but not the entire, cause of IUA. The microorganisms of the female reproductive tract play an important role in its health and disease. The imbalance of immune regulation caused by the imbalance of reproductive tract dysbacteriosis may be an important link in the formation mechanism of uterine cavity adhesion. METHODS: We prospectively enrolled 30 patients diagnosed with IUA and 30 women with a history of intrauterine surgery, but without IUA, as control subjects. All participants were diagnosed with hysteroscopy while two swabs-one being leucorrhea drawn from the middle of the vagina and the other being cervical mucus drawn from the cervical canal-were taken. The bacterial load and community were identified by 16S rDNA quantitative polymerase chain reaction and pyrosequencing. Immunocytokines in serum were quantitatively detected by human T-helper cytokine kit. The correlation between Th cytokines and microorganisms in IUA and non-IUA groups was analyzed. RESULTS: Compared with non-IUA participants at the phylum level, patients with IUA had a significantly higher percentage of firmicutes in most samples, while the diversity of bacteria was significantly decreased. Some species that were members of vaginal and cervical canal bacterial phyla, including Euryarchaeota, Acidobacteria, Chlamydiae, Chlorobi, Planctomycetes and TM6 (Dependentiae), almost disappeared. The quantity in serum of IUA patients of classical proinflammatory cytokines IL-6 and TNF-γ, released from immune cells, also known as profibrotic cytokines, were significantly higher than that of the non-IUA women in our study (P<0.05). CONCLUSIONS: IUA is characterized by an increased bacterial burden, decreased diversity of bacterial communities in the vagina/cervical canal, and increased immune cytokines of pro-fibrosis, which may predict new and more effective therapeutic schemes for the treatment of IUA.