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Microbiota maintains the balance of the vaginal microenvironment and is important for female health. The study of microbiome may provide new ideas for the treatment of diseases. In this paper, aims to understand the vagina microbiome balance of obstetrics and gynecology diseases, microbiota bacterial vaginal disease, reproductive health of women and sexually transmitted infections and progress of gynecological tumors were reviewed. The research progress of microbiome in female reproductive diseases may provide new ideas and opportunities for the treatment of diseases. In this paper, the use of NGS (Next-generation sequencing) and TGS (Third - generation sequencing) sequencing technology research microbiota bacterial vaginal disease, reproductive health of women and sexually transmitted infections and progress of gynecological tumors are reviewed, aims to understand the vagina microbiome balance and the relationship between the flora of promoting the prevention, diagnosis, and treatment of obstetrics and gynecology diseases, the purpose of maintaining the female reproductive health.二、 毕业设计（论文）图纸内容及张数2.1.Introduction:The human body hosts complex microbial communities whose combined membership transcends our own cells by a factor of at least ten.Microorganisms that are exposed to or attached to the external environment at each body site or live in surface cavities. Most healthy reproductive age women are affected by VMB lactobacilli; Although these bacterial communities can vary considerably in individuals and over time.The use of 1S SRRNA sequencing has shown that VMB can be classified according to the dominant bacterial species present.2.2.Vaginal microbiota: Vaginal microbiota have been found as clusters in a limited number of communities, although the community structure is dynamic.Some community species are more associated with poor reproductive outcomes and STDs; Communities affected by the Lactobacillus species, especially Lactobacillus cryptus, are most associated with vaginal health.Mutable and non-variable factors are strongly associated with communal composition, including behavior, race or ethnicity, and hygiene.In this review, we describe the state of science in the vaginal microbiome and its behavior, sexual health, and STD-related relationships, as well as the determinants of the microbiome that go beyond individual levels.2.3. Roles of vaginal microbiota in different disease: Fig 1| The human microbiota: The human microbiome includes five major microbiota：oral cavity, skin, respiratory tract, gastrointestinal tract, and reproductive tract. Under normal circumstances, the microbiome is in the dynamic balance between bacteria and bacteria, bacteria and host, bacteria, and environment. Mild bacterial dysbiosis can be reversed by the body, but long-term bacterial imbalance caused by overregulation of the body can promote the occurrence and development of many diseases.The reproductive tract microbiome is composed of reproductive microflora, host local immune system, host endocrine system, and its anatomical structure9. As the key content of microbiome research, the female vaginal microbiome is normally colonized by one of several lactobacillus genera, characterized by low diversity10 and affected by many factors such as menstruation, age, race, and region. The implementation of the Human microbiome project has promoted the research progress in the field of the human microbiome, especially the reproductive microbiome. At the same time, the second generation and third generation of sequencing technology with its high-throughput, low-cost advantage in many research fields such as the rapid development of sequencing technology and bioinformatics, for the study of the reproductive microbiome field provides a strong analysis tool, to accelerate the human for structure and function of the reproductive microbiome. Studies have shown that, under normal conditions, there is a dynamic balance between the bacterial flora of the reproductive tract, and a slight imbalance of the bacterial flora of the reproductive tract can be reversed by the body itself. When the imbalance exceeds the body's regulatory capacity, it will cause local inflammation and increase susceptibility to various viruses, thus leading to various diseases11(FIG 2). Below will be collected female genital tract microecological study of the relationship between literature and disease using NGS or TGS, mainly from the aspects of bacterial vaginal disease, women's reproductive health, sexually transmitted infection, and gynecological tumors review summarizes four aspects, to recognize the importance of female genital tract microbiota health of the body, and provide a new perspective and new ideas for clinical treatment of gynecological diseases. DysbiosisFig 2| The microbiota of the female reproductive tract: Reproductive tract microbiota is a dynamic balance system composed of normal reproductive tract microflora, host endocrine system, reproductive tract local immune system, and its anatomical structure. The microbiome of the healthy female reproductive tract is characterized by low diversity and is mainly colonized by one of several lactobacillus species. Under the influence of age, menstrual cycle, daily life, and other external factors, it is easy to cause reproductive tract microbiota dysbiosis, leading to the occurrence of various gynecological diseases, and even affect reproductive health.三、 实验内容及要求3.1.Bacterial vaginosis: Bacterial vaginosis (BV), which is more common among the Bacterial vaginosis of women of all ages, mainly affects women of childbearing age and exists in symptomatic or asymptomatic form, is a stubborn disease liable to be contracted repeatedly.BV was first described by Gardner and Dukes in 1955 and was called "Haemophilus Vaginalis Vaginitis" 12-14. It is characterized by pruritus vulva, an abnormal odor of vaginal secretions, PH value greater than 4.5, decreased abundance of lactic acid bacteria, and increased abundance of other opportunistic pathogens. Clinically, there are Nugent scoring system and Amsel standard for BV diagnosis, which are widely used in clinical practice due to their fast detection and low cost15. With the progress of sequencing technology and bioinformatics, the results and functions of vaginal microflora summarized by 16S rRNA gene sequencing can be realized and developed, but until now, the etiology of BV is still unclear.3.1.1. The Bacterial vaginosis engima: Bacterial vaginosis (BV) is the most frequently mentioned cause of vaginal discharge and malignancy, and the most common condition in women of reproductive age is located in the vagina, resulting in millions of health care visits each year in the United States alone. 3.1.2. The complex etiology of BV: Sexual intercourse changes the spread of bacteria and the balance of bacterial flora and leads to an imbalance of vaginosis and the growth of anaerobic bacteria leads to a decrease in hydrogen peroxide lactobacilli. Decreased rates of perimenopausal and postmenopausal estrogen in women and decreased tendency to amenorrhea bacterial vaginosis Lack of blood associated with vaginal flora maintains vaginal pH. The bacterial proliferation and bacterial vaginosis through sexual intercourse can develop spontaneously and become a recurrent disease, and bacterial vaginosis in the microflora tends to develop by altering the balance. 3.1.3. Temporal of vaginal communities: To date, studies of vaginal microbiology have employed cross-sectional designs to take samples from individuals with a single time or with a long break between (weeks or months).Although these studies have provided important information about the synthesis of species in the vaginal community, they provide little insight into the normal temporal dynamics of this Bacterial community in individuals and do not allow estimates of community sustainability. 3.1.4. Toward a system the prevalence of Bacterial vaginosis is largely varied by ethnic group:Although extensive molecular community surveys have provided a wealth of information on the composition of the vaginal microbiota, our understanding of its role and the internal dynamics for conducting its interactions with its host are still unknown. 3.2. Factor that impact on vaginal microbiota in women of reproductive age Lifestyle factor: Factors of fertility related to the reproductive endocrine and genital compound environment affect the vaginal microbiome in women of reproductive age, including the Bacterial species Escherichia coli, Streptococcus agalactiae, and Prevotella intermedia, among others. 3.2.1. Alcohol abuse: Mild to moderate alcohol consumption affects female reproductive function at different stages of life.It has been shown to have a detrimental effect on puberty, disrupt normal stru urination cycling and reproductive activity, and alter hormonal levels in postmenopausal women. 3.2.2. underwear attires: Underwear: Genital hygiene is a major component of women's health and is critical to protecting reproductive health. Both the type of lingerie and the cleanliness of the underwear as well as the frequency with which it is changed affect a woman's risk of urinary tract infection.3.2.3. Harsh soap product: Washing the genital area more than once a day or using different commercial soap products may increase the risk of vaginal infections by irritating the genital flora and therefore is not recommended by the International Society for the Study of Volvo-Vaginal Diseases. 3.2.4. Antibiotics: The balance of the vaginal ecosystem relys on lactobacilli whose biofilm protects against germs that are not normally present or are subdominant in the vaginal flora.The species Lactobacillus maintains a healthy vaginal ecosystem by producing antimicrobial substances.3.3. Hormonal fluctuations: The reproductive system is one of the key systems affected by your body's hormonal balance.A female hormone balance can lead to heavy periods, infertility and endometriosis.(Balance can affect other body systems as well)3.3.1. Menstrual cycle: Estrogen levels doubled during estrogen.In the mid-follicular stage estrogen levels increase and then subside after ovulation.It decreases at the end of the menstrual cycle with a secondary increase in estrogen levels in the mid-luteal stage. 3.3.2. pregnancy: During pregnancy the vaginal microbiome plays an important role in both maternal and neonatal health outcomes Pregnancy is accompanied by a relocation of the Bacterial community. Such a combination of vaginal structures is usually dominated by one or two species of Lactobacillus. 3.3.3. contraceptive: Currently, emerging scientific data suggest that some commonly used contraceptives may increase the risk of sexual HIV acquisition and infection3.4.sexual devices: 3.4.1. Vaginal Lubricants: Vaginal lubricants in particular are widely available and often used by women to reduce dyspnea or increase sexual pleasure.A large number of women use this feminine hygiene product every day.For some people it is a part of their daily cleaning or bathing. 3.4.2. Use of foreign devices (sex toys): Increased international response to ways to reduce the risk of STIS, including HIV, through the use of HIV /AIDS epidemic condoms and potential microbioside3.5.Women's reproductive health: Studies have shown that the vaginal microbiome plays an indispensable role in female fertility, affecting normal pregnancy and pregnancy rate27,28. Female reproductive problems include spontaneous abortion and premature delivery, infertility, low pregnancy rates after in vitro fertilization, and so on (Table 2).Preterm birth is a multifactorial disease. Known risk factors include low age, smoking and alcohol abuse, racial differences, and illicit drug use. In 2014, Romero et al.29 Vaginal treatments for pregnant women treated with clindamycin or metronidazole are both effective and safe to use. Pregnant women should be treated with clindamycin to reduce the risk of bacterial vaginosis of symptomatic pregnancy. Unfortunately, recurrence can occur in 80% of women after treatment. Kenyan and Osbach found a role for BV-related organisms in the exchange of bacteria from a woman's vagina, sexual intercourse, the study found 24.3% of Mycoplasma hominis and 83.3% of Gardnerella rectal samples. BV A malodara Vaginal discharge can reduce sexual activity and quality of life Carrying the risk of chlamydia, gonorrhea, herpes simplex, and HIV infection Short births, spontaneous abortion, delivery, postpartum endometritis. Among the highest risk factors are sexual behavior and reduced risk of recurrence in women who use vaginal douching and contraceptive hormones. BV may increase the risk of STIs, including HIV and pregnancy complications. During pregnancy, the risk of BV preterm delivery doubles, and with three to five times the risk of spontaneous abortion in BV women in the first trimester and chorioamnionitis. Sexual exposure increases the risk of BV, and regular douching and absence of vaginal lactobacilli make Mexican-American and African-American women more prone to white BV than white women and affecting the patterns of vaginal microbiomes that can make a different VMB. The number of Lactobacillus spp decreased and Phingoldia spp, Autopobium spp, Prevotella spp, and Streptococcus spp increased. So far, 16S rRNA sequencing has been used to explore the correlation between normal vaginal microbiome and infertility. In 2018, the Wee34 Meeting the criteria of infertility by using contraceptives. Problems during the treatment of fertile women carry different pregnancy rates of individual diagnosis and treatment to achieve an effective pregnancy, and endometriosis outside the uterine cavity endometrial tissue and endometriosis of the endometrial gland outside the uterus with histological detection endometriosis is found in the most pelvis and affects reproductive age. The pathophysiology stage known as endometriosis as the cause of infertility is thought to vary, with infertility being prevented by the production of prostaglandins and cytokines with inflammatory ovaries and tubules.According to Prevotella, Staphylococcus and Lactobacillus World Health Organization (WHO), infertility is determined by the diagnosis of tubal patency in pregnancy, ovarian function as unexplained infertility is the specific cause for idiopathic infertility (idiopathic infertility). Lactobacillus species are identified in healthy genital mutilation environments for the fetus in the pericanceptal period and during in vitro fertilization may have different effects on Lactobilillus chrysopatas, Lactobilillus genseni, and Lactobilis gastric and some gastrointestinal lactobacillus. Lactobacilli lowers vaginal pH by producing lactic acid, and the birth rate (LBR) is an unfavorable habitat for H2O2-producing pathogens from the embryo transfer-catheter. "White discharge syndrome"studied and analyzed the impact of endometrial microbiota on the reproductive outcomes of infertility patients after in vitro fertilization. It was found that Lactobacillus decrease, Gardnerella, and Streptococcus increase would reduce the embryo implantation rate, pregnancy rate, and live birth rate.Psychological factors Causes of infertility, increased fertility problems, physical stress, such as acute and prolonged exercise Biomedical factors Stress through adequate biological pathways for fertility problems Stress affects reproduction in humans Hypothalamic-pituitary-adrenal axis is good, Fertile and infertile individuals For example, during the in vitro fertilization (IVF) cycle of Boivin and Techfman of negative emotions in women. At the same time, some scholars studied the role of vaginal microbiota in vitro fertilization-embryo transfer (IVF-ET) women and explored its correlation with clinical outcomes. Studies have shown that the vaginal microflora on the day of embryo transplantation affects the pregnancy outcome, and the vaginal microflora with lactobacilli as the dominant microflora is the optimal structure for successful IVF-ET pregnancy39,40 Vaginal microbiotas is the treatment of abnormal vaginal microbiota in healthy and fertile women with in vitro fertilization and in vitro fertilization (IVF) treatment, including spontaneous abortion. Seminal microbiome IUI treatment infertility is related to the rate of clinical pregnancy after IUI.3.6.Sexually transmitted virus infection: Under normal circumstances, the female reproductive tract microbiome is in dynamic balance. When this balance is broken, it will promote the occurrence and development of various diseases, Multiple active STIs in women may increase the level of symptomatic infection of the subclinical genitals and may involve bacterial genital pro-inflammatory cytokines. Molecular sequencing has shown that men carry bacteria in the urethra and some bacteria are associated with non-gonococcal urethritis. Immune mediation of divergent microbiome profiles and may be associated with the risk of HIV acquisition. Infected women and artificial insemination Gardnerella and extra aneurysms to be sexually transmitted as a polymicrobial consortium. Affected women had a higher risk of activated mucosal CD4 cells and HIV under El Crispatus, and three microbiome subtypes were associated with genital inflammation in South African adolescents.such as increasing the risk of human papillomavirus (HPV) and human immunodeficiency virus (HIV) infection (Table 3).In 2013, Lee et al. 43 The important causative agent of uterine cancer (HPV) and the human genetic and physiological factors in vaginal microbiota is unclear. In the study, the variable region of the bacterial 16S rRNA gene was explored in the vaginal microbiota to detect microbial variations in Lactobacillus spp and HPV-positive women who were identified microbiologically with Snothia spp HPV infection... HPV infection is influenced by the genetics involved in vaginal microbiota and the host of menopause. CST lowers lactobacilli and is thought to be immune to anaerobic bacteria-rich, megasephera, anesthesia, and pathogens such as human immunodeficiency virus (HIV) infection, and the presence of Lactobacillus spp. Characteristics of HPV-infected vaginal metabolism and identified high-risk HPV strain (HR-HPV) that vaginal soybeans are made by the bacterium 16S rRNA gene amplicon sequencing and mass spectrometry of chromatography, HPV, DNA. The biogenic amine and phospholipid concentrations and CST levels of HPV and CST and cigarette smoking were different in women.3.6.1. Consequences of dysbiosis: An unhealthy vaginal microbiome, with its significant psycho-social effects, as well as on STDS, is a significant risk factor for the acquisition of STDS and adverse symptoms in women, reproductive and urinary tract infections.7878 Increasingly diverse vaginal microbiota appears to show increasingly low elasticity and greater sensitivity to irritation Diseases. 3.6.2. Bacterial vaginosis and herprs simplex virus:Bacterial vaginosis and herpes simplex virus (HSV) have been linked as epidemics in multiple cross-sectional and potential studies.At the population level, 4 or more nuisant scores were significantly associated with a recent 32% increase in HSV-2 and an 8% increase in HSV-1.79. In a meta-analysis of 16 cross-sectional studies, the authors found that HSV-2-positive Pooled responses to conventional bacterial vaginosis were 60% higher in women than in HSV-2-negative women.Cherps et al followed women for one year and found that the diagnosis of bacterial vaginosis was associated with a double risk of HSV-2 seroconversion... 3.6.3 Bacterial vaginosis and human papillomavirus: The literature that explores the relationship between bacterial vaginosis and human papillomavirus is consistent.Longitudinal studies have shown that both interstitial plant and bacterial diseases are prevalent in women and increase the incidence of HPV, a small but significant increase in the risk of conventional HPV, an increase in the incidence of HPV, and the availability of HPV delayed clearance in women.More than that.Two more recent molecular analyzes showed that women who were HPV positive had lower levels of their protective vaginal Lactobacillus spp.When compared to HPV-negative women, moreover, women with l Gaseri-dominated microbiota appeared to have increased HPV clearance rates. Other studies have shown that cervical intraepithelial dysplasia is associated with increased vaginal myocardial infarction. 3.6.4. Bacterial vaginosis and human immune deficiency virus: There is ample evidence to link vaginal dysbiosis with the acquisition of HIV-1 and the increased risk of infection.A meta-analysis of 23 studies found that bacterial vaginosis was associated with a 60% increase in risk of acquiring HIV-1; These included four longitudinal studies that tested for HIV-1 infection.8 HIV-1 was more effectively trapped in cervicovaginal mucus and mucus affected by other microorganisms than in high-level de-lactic acid, according to L. cryptocurrency.In 91 and lactic acid can inactivate HIV more strongly than other acids in vitro 22 Significantly, a recent study of Rwandan sex workers found that L. crippatas-influenced microbiota had the lowest rates of both HIV and sexually transmitted infections, including HIV and sexually transmitted diseases. 3.6.5. Bacterial vaginosis and bacterial sexually transmitted disease: Epidemiological studies have shown that bacteria have a vaginal relationship with both the risk of gonorrhea and chlamydia infections.Vaginal lactobacilli as well as other bacterial germs were grown in vitro of Neuroria gonorrhea 3.94.A cross-sectional study of 99 found that Newgent's score was more than 3, including a fourfold increase in the risk of gonorrhea and a threefold increase in the risk of chlamydia infection.Well-designed longitudinal studies have shown association with the largest study, which increased the risk of chlamydia and gonorrhea in women with a score of 3.9 higher than Newgent's.WAs... 3.6.6. Bacterial vaginosis and trichomonas: Trichomonas Vaginalis infection was strongly associated with bacterial vaginal infections.In the 2001-2004 National Health and Examinations Survey, cochlear infection was found in about half of the women infected with T. yonilis.Vaginal lactobacilli, and increased neonatal scores have been positively associated with 10 102 Recent longitudinal analyzes have shown that a neonatal score of more than 3 was associated with a significant risk of acquiring vaginitis.Anyway, one study found that CST-IV was significantly associated with T. vonilis detection. Furthermore, T. vaginosis and bacterial vaginosis are independently associated with the increase in vaginal sheds of HIV-1 and their cochlear implants are associated with the proliferation of vaginal discharge. 3.6.7. Bacterial vaginosis and pelvic inflammatory disease: There are some questions as to whether bacterial vaginosis can cause pelvic inflammatory disease (PID) or whether they are the result of an increased qualitative risk of bacterial vaginosis from epidemiologically occurring STD acquisition.Although it is commonly associated with gonorrhea and chlamydia infections, PID was often seen in the absence of known STDs and may be of multimicrobial etiology.-Rich creatures.108 A large longitudinal aggregation study found that bacterial vaginosis-related organisms were associated with a double increase in the PID risk of vaginal conduction events. Another study did not show any relationship between PID and bacterial vaginosis caries in the previous 6 months; However, the dense growth of anaerobic, pigmented gram-negative rods were significantly associated with PID. 3.6.8. Bacterial vaginosis and preterm Birth: Bacterial vaginosis and preterm birth Bacterial vaginosis has long been associated with adverse birth outcomes, although the mechanism by which dysbiosis affects pregnancy remains unclear, and some germs may affect pregnancy outcomes differently at various gestational ages.Related to reduced microbial diversity, 11,20,113 Lactobacillus spp.Dominance and more stability of the vaginal community.In other studies, pre-labor has been associated with different vaginal communities; In addition, no woman with a 20-term delivery had a CST IV-B in a longitudinal study.In a large number of pregnant women with interstitial vaginal flora, the absence of lactobacilli was significantly associated with early delivery.3.7. The composition and structure of vaginal microbiota: Extensive surveys of the vaginal microbial community using culture-specific approaches have shown that Lactobacillus species are predominantly vaginal bacterial species in most females.However, a commendable proportion of asymptomatic, otherwise healthy individuals lack a significant number of Lactobacillus SP in the vaginal microbiota.And surrounds a variety of facial and strictly aerobic microorganisms.3.7.1. Cultural dependent and cultural independent approaches to survey microbial community composition and structures: Majority of our knowledge of the composition, metabolic function, and ecology of indigenous microbial communities associated with humans has come from studies that rely on the cultivation of microbial populations.So our current perception with microbes - host interactions are limited and skewed because the largest number of microbial species (> 99%) oppose agriculture in the laboratory (8).Our limited abilities in culture can be the result3.8. Lactobaccillus-dominated vaginal microbiota: Members of the Lactobacillus species are usually identified as having normal or healthy vaginal features (25; 42; 69; 98).Since they were characterized by the cultivation of vaginal discharge by Donderlin (24; 90; 106), Lactobacillus sp., In the late 19th century.The vagina is thought to play a key role in protecting the vaginal environment from non-native and potentially harmful microbes.There is accomplished through the production of lactic acid, resulting in a less and protective pH (3.5-4.5) (1; 11; 12; 54; 87: 91).Interestingly, lactic acid has been shown to be more effective than antacids alone as a disinfectant against HIV or against germs such as Neisseria gonorrhoeae (38; 60).Gram-negative bacteria, the presence of lactic acid is Faith to have a stimulating effect on the host immune system (120).Recent studies have shown that in vitro colo. 3.8.1. Lactobacillus species anti-microbial substance Production: vaginal Lactobacillus species is known to produce lactic acid as well as other antimicrobial compounds, including target-specific bacteriocins (2; to) and broad-spectrum hydrogen peroxide.Bacteriocins are proteases, narrow spectra of activity by bacteria synthesizing bacterial substances. Their antimicrobial activity is usually based on the permeability of the target cell membrane.Bacteriocins in the vagina may play a major role in inhibiting the growth of indigenous or pathogenic organisms.Many Lactobilis sp.It is also known to produce hydrogen peroxide in vitro under gaseous conditions.It is another antimicrobial compound that can inhibit the colonization of potentially pathogenic bacteria in vivo However, the vagina is practically an anaerobic environment where the level of dissolved oxygen is low.Thus it is unlikely that hydrogen peroxide is produced in significant amounts and accumulates at a toxic level. 3.8.2. Others types of vaginal microbiota: Recent studies have shown that 20-30% of asymptomatic, otherwise healthy women resort to vaginal communities that lack an admirable number of lactobacilli but have a slightly higher pH (5.3-5.5) associated with a variety of felutivative or severely anaerobic bacteria (86); 122-124).The proportion of this community between black and Hispanic women can reach 7 %. These microbiotas include members of Atopobium, Corynebacterium, Anerococcus, Peptonophilus, Prevotella, Gardnerella, Snethia, Eggarthela, Mobiluncas, and Finagolia among others (52; 86; 115; 122-2124).These findings challenge common sense that the presence of a high number of lactobacilli and a vaginal pH
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