This study investigated the differences in vaginal microbiota and metabolism between HPV positive and HPV negative women based on the stratification of vaginitis. This was a case-control study. A total of 164 women were included in this study analysis with a ratio of 1:3 for HPV positive and HPV negative women. The V3-V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) followed by sequencing with Illumina. Untargeted metabolomic sequencing was conducted by the liquid chromatography-mass spectrometry (LC-MS) system. Specific microbial species and differentially expressed metabolites associated with these differences were explored. We found that a statistically significant difference existed in the bacterial structure between HPV positive and HPV negative women (R = 0.2177, p = 0.001), and HPV positivity was associated with the enrichment of Lactobacillus iners among women diagnosed with vaginitis. However, this difference was not observed in women without vaginitis. Regarding metabolic differences, HPV positive women with vaginitis displayed elevated levels of organic acids and their derivatives, accompanied by decreased lipid levels in their vaginal secretions. Conversely, HPV positive women without vaginitis showed higher lipid levels and lower concentrations of organic acids and their derivatives. Among women with vaginitis, Lactobacillus iners was positively correlated with biogenic amine, organic acids and derivatives and negatively correlated with kessyl glycol. Among women without vaginitis, Lactobacillus iners was negatively correlated with pelargonic acid. The disparity in the abundance and metabolites of vaginal microbiota between HPV positive and HPV negative women could be affected by whether the woman has been diagnosed with vaginitis. Metabolic differences indicated that antioxidant therapy holds promising prospects for potential application in the management and treatment of HPV infections. Further in-depth research into the molecular mechanisms is crucial for clarifying the precise role that vaginal microbiota and metabolites play in HPV infection.

Gut microbiota has been causally linked with different psychiatric disorders. However, its potential causal association with panic and conduct disorder remains unexplored. Here we used Mendelian randomization to unravel causal association of specific bacterial taxa with these disorders.

We retrieved genomewide association studies' summary-level dataset for gut microbiota (n = 18,340), panic disorder (n = 451,325), and conduct disorder (n = 216,179) from the MiBioGen and FinnGen consortium for two-sample Mendelian randomization (MR) analysis. We used the inverse-variance weighted (IVW) approach to estimate causal effects complemented by other MR methods. Sensitivity analyses were also carried out to assess the validity of our results.

We detected 15 bacterial taxa with suggestive causal associations. The genera Coprobacter (OR = 1.20, 95%CI = 1.04-1.38; P = 0.011; PFDR = 0.37), Senegalimassilia (OR = 1.32, 95%CI = 1.05-1.65; P = 0.015; PFDR = 0.37) and family Rikenellaceae (OR = 1.17, 95%CI = 1.00-1.38; P = 0.046; PFDR = 0.37) increased the risk of panic disorder while genus Coprococcus (OR = 2.39, 95%CI = 1.16-4.92; P = 0.0179; PFDR = 0.97) and class Coriobacteriia (OR = 2.20, 95%CI = 1.01-4.77; P = 0.045; PFDR = 0.36) increased the risk of conduct disorder. The other 10 bacterial taxa function as a protective factor as they potentially reduce the risk of the two psychiatric disorders. There was also the absence of horizontal pleiotropy and heterogeneity.

The result of this study may not be generalizable across non-European ancestral populations.

Our study provides a bedrock for future clinical prevention and treatment of these disorders.

Recurrent vulvovaginal candidiasis (RVVC) is a common condition that affects women of reproductive age. The etiology of RVVC remains largely unknown, but it is believed to be associated with changes in vaginal microbiota composition. This study investigates the vaginal microbiota in 57 women with RVVC and 38 healthy controls. Bacterial DNA was analyzed using high-throughput 16S rRNA gene sequencing, and Candida and Saccharomyces species were determined by PCR. RVVC cases had a higher prevalence of Nakaseomyses glabratus (former Candida glabrata) compared to controls. Alpha diversity metrics were similar between groups, but beta diversity analysis revealed significant differences in vaginal microbiota composition. The Firmicutes abundance was altered in RVVC cases, with genus Bifidobacterium and phylum Actinobacteriota being more abundant than in the controls. At the genus level, Lactobacillus dominated controls using antibiotics, while Bifidobacterium was higher in cases with no antibiotic intake. Our study provides evidence that Nakaseomyses glabratus (former Candida glabrata) is a significant pathogen in RVVC, while Candida albicans was more prevalent in healthy women. The vaginal microbiota composition differs significantly between the two groups, with distinct patterns of bacterial abundance and changes in Firmicutes abundance.

The effect of blood and mucus on the catheter on pregnancy outcomes in frozen-embryo transfer (FET) cycles remains relatively under-investigated. To evaluate the influence of the presence of blood and mucus on the transfer catheter, along with the characteristics of vaginal microbiota on pregnancy outcomes in FET cycles, we comprehensively analyzed the clinical data of 816 patients. We meticulously recorded the potential traces of blood and mucus on the catheter following embryo transfer (ET). We examined three key outcome parameters including implantation rate (IR), clinical pregnancy rate (CPR), and biochemical pregnancy rate (BPR). Our results demonstrated that the presence of blood on the catheter was associated with a marked decrease in BPR and CPR, whereas the presence of mucus had no significant impact on BPR, CPR, and IR. To further elucidate whether the influence of blood on the catheter on pregnancy outcomes was mediated by vaginal microbiota imbalance, we examined the vaginal microbiota using 16S rRNA gene sequencing and conducted in-depth statistical analyses and correlation studies. Interestingly, the alpha and beta diversity of the vaginal microbiota between the blood group and non-blood group differed significantly. Importantly, the abundance of Lactobacillus was markedly decreased in the blood group. Our results indicate that the negative effect of the blood on the catheter on pregnancy may be attributed to the imbalance of vaginal microbiota. These results provide new insights into the potential mechanisms underlying the association between vaginal microbiota and blood on the catheter and their impact on pregnancy outcomes in FET cycles.

Microorganisms play an important role in regulating various biological processes in our bodies. In women, abnormal changes in the reproductive tract microbiome are associated with various gynecological diseases and infertility. Recent studies suggest that patients with recurrent implantation failure (RIF) have a reduced genus Lactobacillus population, a predominant bacterial species in the vagina and uterus that protects the reproductive tract from pathogenic bacterial growth via the production of various metabolites (e.g., lactic acid, bacteriocin, and H2O2). Moreover, a higher percentage of pathogenic bacteria genera, including Atopobium, Gardnerella, Prevotella, Pseudomonas, and Streptococcus, was found in the uterus of RIF patients. This review aimed to examine the role of pathogenic bacteria in RIF, determine the factors altering the endometrial microbiome, and assess the impact of the microbiome on embryo implantation in RIF. Several factors can influence microbial balance, including the impact of extrinsic elements such as semen and antibiotics, which can lead to dysbiosis in the female reproductive tract and affect implantation. Additionally, probiotics such as Lacticaseibacillus rhamnosus were reported to have clinical potential in RIF patients. Future studies are needed to develop targeted probiotic therapies to restore microbial balance and enhance fertility outcomes. Research should also focus on understanding the mechanisms by which microorganisms generate metabolites to suppress pathogenic bacteria for embryo implantation. Identifying these interactions may contribute to innovative microbiome-based interventions for reproductive health.

Background/Objectives: Persistent high-risk human papillomavirus (HPV) infections are the leading cause of cervical cancer. Developing evidence suggests that the cervicovaginal microbiome plays a significant role in modulating HPV persistence and progression to cervical neoplasia. This review synthesizes the current knowledge on the interplay between the cervicovaginal microbiome and local immunity in HPV infections, emphasizing microbial diversity, immune responses, and potential therapeutic implications. Methods: A thorough review of the literature was performed using Embase, PubMed, Scopus, and Google Scholar, encompassing studies published between 2000 and 2024. Studies examining the composition of the microbiome, immune responses, and HPV-related outcomes were evaluated and synthesized into a comprehensive review. Results: A Lactobacillus-dominant microbiome, particularly with L. crispatus, creates a protective environment through lactic acid production, maintenance of low pH, and anti-inflammatory immune modulation, facilitating HPV clearance. Dysbiosis, often characterized by a dominance of L. iners and overgrowth of anaerobic bacteria, fosters chronic inflammation, cytokine imbalance, and a microenvironment conducive to HPV persistence and progression. Hormonal changes and menopause exacerbate these microbial shifts, increasing the risk of cervical lesions. Studies suggest that cytokine profiles and antimicrobial peptides significantly influence local immune responses, further modulating infection outcomes. Conclusions: The cervicovaginal microbiome is a critical determinant in HPV infection outcomes, with therapeutic potential for modulating the microbiome to enhance immune responses and prevent cervical cancer. Personalized microbiome-targeted therapies may offer a novel avenue for managing HPV and reducing cervical cancer incidence.

Infertility affects 8-12% of couples worldwide, and 30-75% of preclinical pregnancy losses are due to a failure during the implantation process. Exposure to endocrine disruptors, like bisphenols, among others, has been associated with the increase in infertility observed in the past decades. An increase in infertility has correlated with exposure to endocrine disruptors like bisphenols. The uterus harbors its own microbiota, and changes in this microbiota have been linked to several gynecological conditions, including reproductive failure. There are no studies on the effects of bisphenols on the uterine-microbiota composition, but some inferences can be gleaned by looking at the gut. Bisphenols can alter the gut microbiota, and the molecular mechanism by which gut microbiota regulates intestinal permeability involves Toll-like receptors (TLRs) and tight junction (TJ) proteins. TJs participate in embryo implantation in the uterus, but bisphenol exposure disrupts the expression and localization of TJ proteins. The aim of this review is to summarize the current knowledge on the microbiota of the female reproductive tract (FRT), its association with different reproductive diseases-particularly reproductive failure-the effects of bisphenols on microbiota composition and reproductive health, and the molecular mechanisms regulating uterine-microbiota interactions crucial for embryo implantation. This review also highlights existing knowledge gaps and outlines research needs for future risk assessments regarding the effects of bisphenols on reproduction.

Infertility poses a global challenge that impacts a significant proportion of the populace. Presently, there is a substantial emphasis on investigating the potential of probiotics and their derivatives, called postbiotics, as an alternative therapeutic strategy for addressing infertility. The term of "postbiotics" refers to compounds including peptides, enzymes, teichoic acids, and muropeptides derived from peptidoglycans, polysaccharides, proteins, and organic acids that are excreted by living bacteria or released after bacterial lysis. Postbiotics exhibit the capacity to enhance fertility in both men and women, with their impact on male reproductive function (specifically testicular function, semen quality, and prostate health) and female reproductive health (including modulation of vaginal microbiota and restoration thereof) being posited as potential mechanisms by which postbiotics may enhance fertility. This review highlights definitions of postbiotics, as well as their biological role in treatment of infertility.

Women's health is essential to global societal and economic wellbeing, yet health disparities remain prevalent. The vaginal microbiota plays a critical role in health, with research indicating that reduced levels of core bacteria, such as lactobacilli, are associated with conditions like bacterial vaginosis (BV) and increased infection susceptibility. Lower levels of vaginal lactobacilli are reported more frequently in women of African and Latin American descent compared with women of European and Asian descent. However, geographical and other study inclusion and analysis biases influence current research. This opinion highlights the need for a more comprehensive understanding of a 'healthy' vaginal microbiome. It underscores efforts to broaden global research on microbiome diversity in socially relevant contexts, avoiding inappropriate applications of terms such as race and ethnicity.

Infertility, both primary and secondary, is strongly influenced by microbiological factors, with the vaginal microbiota playing a key role in reproductive health.

The aim of this study was to characterize the vaginal microbiota of 136 Mexican women diagnosed with infertility-primary (n = 58) and secondary (n = 78)-by evaluating the presence of pathogenic bacterial species and their associations with infertility conditions.

Samples were obtained through cervical swabs, and microorganism identification was performed using qPCR techniques.

Analysis revealed a positive correlation between increased age and the likelihood of primary infertility, as well as a negative correlation with secondary infertility. Significant differences in microbial composition were also observed between the two infertility groups. Lactobacillus crispatus and Lactobacillus gasseri were dominant in women with primary infertility, in addition to a high prevalence of Gardnerella vaginalis and Fannyhessea vaginae. Additionally, correlations were found between the presence of human papillomavirus (HPV) and sexually transmitted bacteria, as well as Gardnerella vaginalis.

Our findings suggest that the composition of the vaginal microbiota may play a decisive role in infertility, highlighting the need for personalized therapeutic strategies based on microbial profiles.

This review investigates the therapeutic potential of butyrate, a short-chain fatty acid (SCFA) produced by gut microbiota, in the prevention and treatment of various gynecological diseases, including polycystic ovary syndrome (PCOS), endometriosis, and gynecologic cancers like cervical and ovarian cancer. These conditions often pose treatment challenges, with conventional therapies offering limited and temporary relief, significant side effects, and a risk of recurrence. Emerging evidence highlights butyrate's unique biological activities, particularly its role as a histone deacetylase (HDAC) inhibitor, which allows it to modulate gene expression, immune responses, and inflammation. In PCOS, butyrate aids in restoring hormonal balance, enhancing insulin sensitivity, and reducing chronic inflammation. For endometriosis, butyrate appears to suppress immune dysregulation and minimize lesion proliferation. Additionally, in cervical and ovarian cancers, butyrate demonstrates anticancer effects through mechanisms such as cell cycle arrest, apoptosis induction, and suppression of tumor progression. Dietary interventions, particularly high-fiber and Mediterranean diets, that increase butyrate production are proposed as complementary approaches, supporting natural microbiota modulation to enhance therapeutic outcomes. However, butyrate's short half-life limits its clinical application, spurring interest in butyrate analogs and probiotics to maintain stable levels and extend its benefits. This review consolidates current findings on butyrate's multifaceted impact across gynecological health, highlighting the potential for microbiota-centered therapies in advancing treatment strategies and improving women's reproductive health.

The vaginal flora has been reported to be associated with human papillomavirus (HPV) infection. The purpose of this study was to investigate the characteristics of the cervical microbiota in patients with HPV infection and to analyse the changes in the vaginal flora and enzyme profiles in females with HPV infection.

We conducted a cross-sectional study involving 206 participants who underwent HPV genotyping, sexually transmitted diseases pathogen testing, cytology examination, and microbiome analysis. Additionally, we collected 115 HPV-negative samples and 48 HPV-positive samples for 16S rRNA amplicon sequencing. The vaginal microbial communities of both groups were analysed for diversity and differences to explore their association with HPV infection.

The abundance of Lactobacillus was found to be reduced, while Gardnerella vaginalis was significantly more prevalent in the HPV + group. In terms of alpha diversity indices, the Shannon index (P = .0036) and Simpson index (P = .02) were higher in the HPV + group compared to the HPV - group, indicating greater community diversity in the HPV + group. Among the 10 sexually transmitted diseases pathogens analysed, Uup3 and Uup6 were significantly associated with HPV infection. Statistically significant differences were observed in Nugent scores and bacterial vaginosis between the two groups (P < .05). In functional analysis, 11 proteins and 13 enzymes were found to be significantly altered in the HPV + group.

Our study demonstrates that disruptions in the vaginal flora are associated with HPV infection. Reduced levels of Lactobacillus, increased prevalence of Gardnerella, and abnormal enzyme profiles are closely linked to HPV infection.

The human vaginal microbiome (VMB) is a complex and unique ecosystem composed of various microorganisms, including bacteria, fungi, archaea, viruses, and candidate phyla radiation. A healthy VMB is often characterized by the presence of Lactobacillus species, which play a crucial role in protecting and maintaining homeostasis within the vaginal environment. When this balance is disrupted, the protection of the vaginal epithelium weakens, leading to a reduction in Lactobacillus species and an increased risk of various gynecological and reproductive health issues. However, this generalized description can lead to misconceptions and an incomplete understanding of vaginal health, as Lactobacillus is not always dominant across all ages and racialized groups. Therefore, this review provides a comprehensive analysis of the environmental, biological, and racial influences on the VMB at each stage of a woman's life, highlighting their implications for gynecological health and offering a holistic understanding of the VMB for all women.

Over the past decade, research on the human microbiota has become a hot topic. Among them, the female reproductive tract (FRT) also has a specific microbiota that maintains the body's health and dynamic balance, especially in the reproductive aspect. When the FRT ecosystem is dysregulated, changes in immune and metabolic signals can lead to pathological and physiological changes such as chronic inflammation, epithelial barrier disruption, changes in cell proliferation and apoptosis, and dysregulation of angiogenesis and metabolism, thereby causing disruption of the female endocrine system. Premature ovarian insufficiency (POI), a clinical syndrome of ovarian dysfunction, is primarily influenced by immune, genetic, and environmental factors. New evidence suggests that dysbiosis of the FRT microbiota and/or the presence of specific bacteria may contribute to the occurrence and progression of POI. This influence occurs through both direct and indirect mechanisms, including the regulation of estrogen metabolism. The use of probiotics or microbiota transplantation to regulate the microbiome has also been proven to be beneficial in improving ovarian function and the quality of life in women with premature aging. This article provides an overview of the interrelationships and roles between the FRT microbiome and POI in recent years, to fully understand the risk factors affecting female reproductive health, and to offer insights for the future diagnosis, treatment, and application of the FRT microbiome in POI patients.

This is a single Institute, prospective cohort study. We enrolled twenty-two postmenopausal women with pelvic organ prolapse planning to undergo vaginal hysterectomy with transvaginal pelvic reconstructive surgery, with or without a concomitant anti-incontinence procedure. Vaginal swabs and urine samples were longitudinally collected at five time points: preoperative consult visit (T1), day of surgery prior to surgical scrub (T2), immediately postoperative (T3), day of hospital discharge (T4), and at the postoperative exam visit (T5). Women experiencing urinary tract infection symptoms provided a sample set prior to antibiotic administration (T6). Microbiome analysis was performed on vaginal and urinary specimens at each time point. Region V3-V5 of the 16S ribosomal RNA gene was amplified and sequenced. DNA samples were analyzed for visit T1, T2, T5 and T6. Six (27.3%) participants developed postoperative urinary tract infection whose vaginal sample at first clinical visit (T1) revealed beta-diversity analysis with significant differences in microbiome structure and composition. Women diagnosed with a postoperative urinary tract infection had a vaginal microbiome characterized by low abundance of Lactobacillus and high prevalence of Prevotella and Gardnerella species. In our cohort, preoperative vaginal swabs can predict who will develop a urinary tract infection following transvaginal surgery for pelvic organ prolapse.ClinicalTrials.gov Identifier: NCT02751073.

The purpose of this study was to conduct a comparative analysis of the composition of the dominant groups of vaginal microorganisms in healthy pregnant women and pregnant women infected with HPV using a microbiological culture-based method. The MALDI TOF MS method and 16S rRNA gene fragment sequencing were used to identify microorganisms isolated from healthy pregnant women (n=32) and pregnant women infected with HPV (n=24). It was found that vaginal secretion samples from both groups contained bacteria of 4 phyla: Bacillota, Actinomycetota, Pseudomonadota, Bacteroidota, and Ascomycota fungi. The most common microbial community in healthy pregnant women being CST I (p=0.0007), and CST V in pregnant women infected with HPV (p=0.0001). At the genus level, a total of 25 taxa were found in all samples, with Lactobacillus being the dominant genus overall. Escherichia (p<0.0001) and Prevotella (p=0.0001) concentrations were higher in HPV infected patients. When calculating the Pearson correlation coefficient for the phyla, it was found that Bacillota correlated negatively with HPV genotypes 16 and 51 (p≤0.05), but positively with HPV genotype 59 (p≤0.05), just like Actinomycetota (p≤0.05). Bacteroidota correlated positively with HPV genotype 56 (0.001 Collapse

Neovaginas are surgically constructed to correct uterovaginal agenesis in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome or as part of gender-affirming surgery for transfeminine individuals. Understanding the assembly of the neovaginal microbiota is crucial for guiding its management. To address this, we conducted a longitudinal study on MRKH patients following laparoscopic peritoneal vaginoplasty. Our findings reveal that the early microbial assemblage exhibited stochastic characteristics, accompanied with a notable bloom of Enterococcus faecalis and genital Mycoplasmas. While both the pre-surgery dimple microbiota and the fecal microbiota constituted the primary species pool, the neovaginal microbiota developed into a microbiota that resembled that of a normal vagina at 6-12 months post-surgery, albeit with a bacterial vaginosis (BV)-like structure. By 2-4 years post-surgery, the neovaginal microbiota had further evolved into a structure closely resembling with the homeostatic pre-surgery dimple microbiota. This concords with the development of the squamous epithelium in the neovagina and highlights the pivotal roles of progressive selective forces imposed by the evolving neovaginal environment and the colonization tropism of vaginal species. Notably, we observed that strains of Lactobacillus crispatus colonizing the neovagina primarily originated from the dimple. Since L. crispatus is generally associated with vaginal health, this finding suggests potential avenues for future research to promote its colonization.

Trichomonas vaginalis is an extracellular protozoan parasite of the human urogenital tract, responsible for a prevalent sexually transmitted infection. Trichomoniasis is accompanied by a dysbiotic microbiome that is characterised by the depletion of host-protective commensals such as Lactobacillus gasseri, and the flourishing of a bacterial consortium that is comparable to the one seen for bacterial vaginosis, including the founder species Gardnerella vaginalis. These two vaginal bacteria are known to have opposite effects on T. vaginalis pathogenicity. Studies on extracellular vesicles (EVs) have been focused on the direction of a microbial producer (commensal or pathogen) to a host recipient, and largely in the context of the gut microbiome. Here, taking advantage of the simplicity of the human cervicovaginal microbiome, we determined the molecular cargo of EVs produced by L. gasseri and G. vaginalis and examined how these vesicles modulate the interaction of T. vaginalis and host cells. We show that these EVs carry a specific cargo of proteins, which functions can be attributed to the opposite roles that these bacteria play in the vaginal biome. Furthermore, these bacterial EVs are delivered to host and protozoan cells, modulating host-pathogen interactions in a way that mimics the opposite effects that these bacteria have on T. vaginalis pathogenicity. This is the first study to describe side-by-side the protein composition of EVs produced by two bacteria belonging to the opposite spectrum of a microbiome and to demonstrate that these vesicles modulate the pathogenicity of a protozoan parasite. Such as in trichomoniasis, infections and dysbiosis co-occur frequently resulting in significant co-morbidities. Therefore, studies like this provide the knowledge for the development of antimicrobial therapies that aim to clear the infection while restoring a healthy microbiome.

Cumulative evidence attests to the essential roles of commensal microbes in the physiology of hosts. Although the microbiome has been a major research subject since the time of Luis Pasteur and William Russell over 140 years ago, recent findings that certain intracellular bacteria contribute to the pathophysiology of healthy vs. diseased tissues have brought the field of the microbiome to a new era of investigation. Particularly, in the field of breast cancer research, breast-tumor-resident bacteria are now deemed to be essential players in tumor initiation and progression. This is a resurrection of Russel's bacterial cause of cancer theory, which was in fact abandoned over 100 years ago. This review will introduce some of the recent findings that exemplify the roles of breast-tumor-resident microbes in breast carcinogenesis and metastasis and provide mechanistic explanations for these phenomena. Such information would be able to justify the utility of breast-tumor-resident microbes as biomarkers for disease progression and therapeutic targets.

Gestational diabetes mellitus (GDM) is an important health issue, as it is connected with adverse effects to the mother as well as the fetus. A factor of essence for the pathology of this disorder is the gut microbiota, which seems to have an impact on the development and course of GDM. The role of the gut microbiota on maternal reproductive health and all the changes that happen during pregnancy as well as during the neonatal period is of high interest. The correct establishment and maturation of the gut microbiota is of high importance for the development of basic biological systems. The aim of this study is to provide a systematic review of the literature on the effect of GDM on the gut microbiota of neonates, as well as possible links to morbidity and mortality of neonates born to mothers with GDM. Systematic research took place in databases including PubMed and Scopus until June 2024. Data that involved demographics, methodology, and changes to the microbiota were derived and divided based on patients with exposure to or with GDM. The research conducted on online databases revealed 316 studies, of which only 16 met all the criteria and were included in this review. Research from the studies showed great heterogeneity and varying findings at the level of changes in α and β diversity and enrichment or depletion in phylum, gene, species, and operational taxonomic units in the neonatal gut microbiota of infants born to mothers with GDM. The ways in which the microbiota of neonates and infants are altered due to GDM remain largely unclear and require further investigation. Future studies are needed to explore and clarify these mechanisms.

The microbiota plays an important role in numerous physiological processes, pathogenesis, development, and metabolism in different animal species. In humans, several studies have demonstrated an association between the vaginal microbiota and fertility rates, and even success in assisted reproduction techniques. In the context of cattle reproduction, although few studies have addressed the microbiota in a healthy state (which is not associated with diseases that affect the reproductive tract of cows), changes in its composition also seem to influence fertility. This review aims to explain the importance of the reproductive microbiota in female bovines and what is available in the literature regarding its possible role in increasing fertility. What are the challenges involved in this process? Future perspectives on its use and manipulation as a selection or intervention tool. Will it be possible to one day extrapolate the findings to reality and apply them in the field? In short, understanding the role of the reproductive microbiota of female bovines can signal the prospect of increasing production, whether of milk or meat, from the same number of animals, as it can optimize reproductive efficiency and perhaps become an allied tool for the economic profitability and sustainability of livestock farming.

To explore the differences of vaginal microbes in women with preterm birth (PTB), and to construct prediction model. We searched for articles related to vaginal microbiology in preterm women and obtained four 16S rRNA-sequence datasets. We analyzed that for species diversity and differences, and constructed a random forest model with 20 differential genera. We introduce an independent whole genome-sequencing (WGS) data for validation. In addition, we collected vaginal and cervical swabs from 33 pregnant women who delivered spontaneously full-term and preterm infants, performed WGS in our lab to further validate the model. Compared to term birth (TB) samples, PTB women vagina were characterized by a decrease in Firmicutes, Lactobacillus, and an increase in diversity accompanied by the colonization of pathogenic bacteria such as Gardnerella, Atopobium and Prevotella. Twenty genus markers, including Lactobacillus, Prevotella, Streptococcus, and Gardnerella performed well in predicting PTB, with study-to-study transfer validation and LODO validation, different gestation validation showing good results, and in two independent cohorts (external WGS cohorts and woman samples WGS cohorts) in which the accuracy was maintained. PTB women have unique vaginal microbiota characteristics. A predictive model of PTB was constructed and its value validated from multiple perspectives.

We assessed the in vitro anti-chlamydial activity of fresh vaginal secretions, deciphering the microbial and metabolic components able to counteract Chlamydia trachomatis viability.

Forty vaginal samples were collected from a group of reproductive-aged women and their anti-chlamydial activity was evaluated by inhibition experiments. Each sample underwent 16S rRNA metabarcoding sequencing to determine the bacterial composition, as well as 1H-NMR spectroscopy to detect and quantify the presence of vaginal metabolites.

Samples characterized by a high anti-chlamydial activity were enriched in Lactobacillus, especially Lactobacillus crispatus and Lactobacillus iners, while not-active samples exhibited a significant reduction of lactobacilli, along with higher relative abundances of Streptococcus and Olegusella. Lactobacillus gasseri showed an opposite behavior compared to L. crispatus, being more prevalent in not-active vaginal samples. Higher concentrations of several amino acids (i.e., isoleucine, leucine, and aspartate; positively correlated to the abundance of L. crispatus and L. jensenii) lactate, and 4-aminobutyrate were the most significant metabolic fingerprints of highly active samples. Acetate and formate concentrations, on the other hand, were related to the abundances of a group of anaerobic opportunistic bacteria (including Prevotella, Dialister, Olegusella, Peptostreptococcus, Peptoniphilus, Finegoldia and Anaerococcus). Finally, glucose, correlated to Streptococcus, Lachnospira and Alloscardovia genera, emerged as a key molecule of the vaginal environment: indeed, the anti-chlamydial effect of vaginal fluids decreased as glucose concentrations increased.

These findings could pave the way for novel strategies in the prevention and treatment of chlamydial urogenital infections, such as lactobacilli probiotic formulations or lactobacilli-derived postbiotics.

Vaginally administered postbiotics derived from Lactobacillus were recently demonstrated to be effective in alleviating bacterial vaginosis and increasing pregnancy rates. However, their potential effect on sperm quality has not been well investigated. This controlled in vitro study aimed to assess the dose- and time-dependent effects of postbiotics derived from Lactobacillus rhamnosus PB01 (DSM 14870) on sperm quality parameters. The experiment was conducted in vitro to eliminate potential confounding factors from the female reproductive tract and vaginal microbiota. Sperm samples from 18 healthy donors were subjected to analysis using Computer-Aided Sperm Analysis (CASA) in various concentrations of postbiotics and control mediums at baseline, 60 min, and 90 min of incubation. Results indicated that lower postbiotic concentration (PB5) did not adversely affect sperm motility, kinematic parameters, sperm DNA fragmentation, and normal morphology at any time. However, concentrations exceeding 15% demonstrated a reduction in progressively motile sperm and a negative correlation with non-progressively motile sperm at all time points. These findings underscore the importance of balancing postbiotic dosage to preserve sperm motility while realizing the postbiotics' vaginal health benefits. Further research is warranted to understand the underlying mechanisms and refine practical applications in reproductive health.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

The microbiome plays a critical role in the process of conception and the outcomes of pregnancy. Disruptions in microbiome homeostasis in women of reproductive age can lead to various pregnancy complications, which significantly impact maternal and fetal health. Recent studies have associated the microbiome in the female reproductive tract (FRT) with assisted reproductive technology (ART) outcomes, and restoring microbiome balance has been shown to improve fertility in infertile couples. This review provides an overview of the role of the microbiome in female reproductive health, including its implications for pregnancy outcomes and ARTs. Additionally, recent advances in the use of microbial biomarkers as indicators of pregnancy disorders are summarized. A comprehensive understanding of the characteristics of the microbiome before and during pregnancy and its impact on reproductive health will greatly promote maternal and fetal health. Such knowledge can also contribute to the development of ARTs and microbiome-based interventions.

Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women's physical and mental health. Understanding the relationship between SUI and vaginal microbiota composition may help to prevent vaginal diseases, but research on the potential association between these conditions is limited.

This study employed 16S rRNA gene sequencing to explore the association between SUI and vaginal dysbiosis. In terms of the vaginal microbiota, both species richness and evenness were significantly higher in the SUI group. Additionally, the results of NMDS and species composition indicated that there were differences in the composition of the vaginal microbiota between the two groups. Specifically, compared to postpartum women without SUI (Non-SUI), the relative abundance of bacteria associated with bacterial dysbiosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the relative abundance of Lactobacillus decreased in SUI patients. Furthermore, the vaginal microbial co-occurrence network of SUI patients displayed higher connectivity, complexity, and clustering.

The study highlights the role of Lactobacillus in maintaining vaginal microbial homeostasis. It found a correlation between SUI and vaginal microbiota, indicating an increased risk of vaginal dysbiosis. The findings could enhance our understanding of the relationship between SUI and vaginal dysbiosis in postpartum women, providing valuable insights for preventing bacterial vaginal diseases and improving women's health.

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.

Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively.

The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection.

The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

Relevant studies increasingly indicate that female reproductive health is confronted with substantial challenges. Emerging research has revealed that the microbiome interacts with the anatomy, histology, and immunity of the female reproductive tract, which are the cornerstone of maintaining female reproductive health and preventing adverse pregnancy outcomes. Currently, the precise mechanisms underlying their interaction and impact on physiological functions of the reproductive tract remain elusive, constituting a prominent area of investigation within the field of female reproductive tract microecology. From this new perspective, we explore the mechanisms of interactions between the microbiome and the anatomy, histology, and immunity of the female reproductive tract, factors that affect the composition of the microbiome in the female reproductive tract, as well as personalized medicine approaches in managing female reproductive tract health based on the microbiome. This study highlights the pivotal role of the female reproductive tract microbiome in maintaining reproductive health and influencing the occurrence of reproductive tract diseases. These findings support the exploration of innovative approaches for the prevention, monitoring and treatment of female reproductive tract diseases based on the microbiome.

Contemporary research in the field of microbiota shows that commensal bacteria influence physiological activity of different organs and systems of a human organism, such as brain, lungs, immune and metabolic systems. This influence is realized by various processes. One of them is trough modulation of immune mechanisms. Interactions between microbiota and the human immune system are known to be complex and ambiguous. Dendritic cells (DCs) are unique cells, which initiate the development and polarization of adaptive immune response. These cells also interconnect native and specific immune reactivity. A large set of biochemical signals from microbiota in the form of different microbiota associated molecular patterns (MAMPs) and bacterial metabolites that act locally and distantly in the human organism. As a result, commensal bacteria influence the maturity and activity of dendritic cells and affect the overall immune reactivity of the human organism. It then determines the response to pathogenic microorganisms, inflammation, associated with different pathological conditions and even affects the effectiveness of vaccination.

The connection between maternal microbiota and infant health has been greatly garnered interest for therapeutic purposes. The early resident microbiota perpetually exhibits much more flexibility as compared to that of the adults, and therefore, constant need of understanding the infant as well as maternal microbiota and their implications however has increased. In this review, we focus mainly on the diversity of overall maternal microbiota including the gut, vaginal, colostrum microbiota and how inflammatory markers fluctuate throughout the normal pregnancy as well in pregnancy with complications. The maternal body undergoes a cascade of physiological changes including hormonal, immunological and metabolic events to support the fetal development. These changes at the time of pregnancy have been correlated with alteration in the composition and diversity of maternal microbiota. Along with alteration in microbiome, the levels of circulatory cytokines fluctuate by complex network of inflammation, in order to prevent the fetal allograft throughout the pregnancy. The dynamic relationship of gut microbiota with the host and its immune system allows one to have greater insights of their role in pregnancy and newborn's health. Emerging evidence suggests that the vertical transmission of bacterial community from mother to newborn may begin in-utero which contributes in developing the immune system and infant gut microbiota.

A healthy vaginal microbiota hosts Lactobacillus as the most predominant genus. Lactobacilli play a role in human health through the production of diverse antimicrobial substances that can act against human pathogens or modulate the immune system. Previous reports highlighted the ability of vaginal lactobacilli to counteract viruses causing STIs, e.g., HIV-1 and HSV-2. In this report, we analyze the activity of supernatants of vaginal lactobacilli against HSV-1 infection, which is becoming increasingly relevant as a STI. We show that the supernatants of two vaginal Lactobacillus species (i.e., L. crispatus and L. gasseri) were active at neutralizing HSV-1 infection in two different cell lines of human and simian origin. Specifically, we demonstrate that L. crispatus strains are the most effective in antiviral activity, as evidenced by the comparison with a vaginal pathogen taken as reference. The effect was specific and not attributable to the generic toxicity of the supernatants to the cells. Our results pave the way for the development of probiotics to limit the impact of HSV-1 infection on women's health.

To examine the gut microbiota characteristics in children with immunoglobulin A vasculitis and their interrelationships with the host, while evaluate the vertical inheritance of microbiota in the development and progression of IgA vasculitis.

This study investigated the gut microbiome of 127 IgA vasculitis mother-child pairs and 62 matched healthy mother-child pairs, and compared the gut microbial composition of different groups. The pathway enrichment analysis evaluated potential gut microbiome-mediated pathways involved in the pathophysiology of IgA vasculitis. The Spearman correlation analysis illustrated the relationships between clinical variables and bacterial biomarkers.

This study identified distinct intestinal microbiome in IgA vasculitis children compared to healthy children, and further pointed out the association in gut microbiota between IgA vasculitis children's and their mother's. The relative abundance of Megamonas and Lactobacillus in IgAV children was positively correlated with that in their mothers. The pathway enrichment analysis found microbial biosynthesis of vitamins and essential amino acids was upregulated in children with IgA vasculitis. Correlation analysis showed bacterial biomarkers were correlated with indicators of blood coagulation.

Children with IgA vasculitis have unique bacterial biomarkers and may affect coagulation function, and their gut microbiome was closely associated with that of their mothers. The observed association in gut microbiota between IgA vasculitis children and their mothers suggested a potential intergenerational influence of the maternal microbiota on the development or progression of IgA vasculitis in children.

The vaginal microbiota plays a crucial role in female reproductive health and is considered a biomarker for predicting disease outcomes and personalized testing. However, its relationship with human papillomavirus (HPV) infection and cervical cancer is not yet clear. Therefore, this article provides a review of the association between the vaginal microbiota, HPV infection, and cervical cancer. We discuss the composition of the vaginal microbiota, its dysbiosis, and its relationship with HPV infection, as well as potential mechanisms in the development of cervical cancer. In addition, we assess the feasibility of treatment strategies such as probiotics and vaginal microbiota transplantation to modulate the vaginal microbiota for the prevention and treatment of diseases related to HPV infection and cervical cancer. In the future, extensive replication studies are still needed to gain a deeper understanding of the complex relationship between the vaginal microbiota, HPV infection, and cervical cancer, and to clarify the role of the vaginal microbiota as a potential biomarker for predicting disease outcomes, thus providing a theoretical basis for personalized testing.

Given that the host-microbe interaction is shaped by the immune system response, it is important to understand the key immune system-microbiota relationship during the period from conception to the first years of life. The present work summarizes the available evidence concerning human reproductive microbiota, and also, the microbial colonization during early life, focusing on the potential impact on infant development and health outcomes. Furthermore, we conclude that some dietary strategies including specific probiotics and other-biotics could become potentially valuable tools to modulate the maternal-neonatal microbiota during this early critical window of opportunity for targeted health outcomes throughout the entire lifespan.

Vaginal microbial composition is associated with differential risk of urogenital infection. Although Lactobacillus spp. are thought to confer protection against infection, the lack of in vivo models resembling the human vaginal microbiota remains a prominent barrier to mechanistic discovery. Using 16S rRNA amplicon sequencing of C57BL/6J female mice, we found that vaginal microbial composition varies within and between colonies across three vivaria. Noting vaginal microbial plasticity in conventional mice, we assessed the vaginal microbiome of humanized microbiota mice (HMbmice). Like the community structure in conventional mice, HMbmice vaginal microbiota clustered into community state types but, uniquely, HMbmice communities were frequently dominated by Lactobacillus or Enterobacteriaceae. Compared to conventional mice, HMbmice were less susceptible to uterine ascension by urogenital pathobionts group B Streptococcus (GBS) and Prevotella bivia. Although Escherichia and Lactobacillus both correlated with the absence of uterine GBS, vaginal pre-inoculation with exogenous HMbmouse-derived E. coli, but not Ligilactobacillus murinus, reduced vaginal GBS burden. Overall, HMbmice serve as a useful model to elucidate the role of endogenous microbes in conferring protection against urogenital pathogens.

Understanding the composition and function of the vaginal microbiome is crucial for reproductive and overall health. Here we established the Isala citizen-science project to analyse the vaginal microbiomes of 3,345 women in Belgium (18-98 years) through self-sampling, 16S amplicon sequencing and extensive questionnaires. The overall vaginal microbiome composition was strongly tied to age, childbirth and menstrual cycle phase. Lactobacillus species dominated 78% of the vaginal samples. Specific bacterial taxa also showed to co-occur in modules based on network correlation analysis. Notably, the module containing Lactobacillus crispatus, Lactobacillus jensenii and Limosilactobacillus taxa was positively linked to oestrogen levels and contraceptive use and negatively linked to childbirth and breastfeeding. Other modules, named after abundant taxa (Gardnerella, Prevotella and Bacteroides), correlated with multiple partners, menopause, menstrual hygiene and contraceptive use. With this resource-rich vaginal microbiome map and associated health, life-course, lifestyle and dietary factors, we provide unique data and insights for follow-up clinical and mechanistic research.