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23 pages, 2284 KB  
Systematic Review
The Role of Endometrial Microbiota in the Pathogenesis of Chronic Endometritis: A Systematic Review and Meta-Analysis
by Angela Vidal, Anaïs Y. Kilian, Vithusha Vinayahalingam, Branislav Zagrapan, Janna Pape, Tanya Karrer and Michael von Wolff
Biomedicines 2026, 14(4), 871; https://doi.org/10.3390/biomedicines14040871 - 10 Apr 2026
Abstract
Background: Chronic endometritis (CE) is a subtle, often asymptomatic endometrial inflammation marked by CD138+ plasma cell infiltration and linked to recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and unexplained infertility. Emerging evidence implicates endometrial microbiome dysbiosis in CE. Objective: To systematically [...] Read more.
Background: Chronic endometritis (CE) is a subtle, often asymptomatic endometrial inflammation marked by CD138+ plasma cell infiltration and linked to recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and unexplained infertility. Emerging evidence implicates endometrial microbiome dysbiosis in CE. Objective: To systematically review and conduct meta-analysis on the association between CE and endometrial microbiome alterations and their reproductive implications. Methods: We searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar for studies diagnosing CE via CD138 immunostaining, assessing microbiota with molecular techniques. Data extraction, quality assessment, and meta-analysis were performed. Results: Twenty-two studies including 4022 women were analyzed. CE was associated with reduced prevalence of Lactobacillus-dominated microbiota and increased detection of non-Lactobacillus species, particularly Streptococcus spp., Enterococcus spp., Escherichia coli, Staphylococcus spp., Ureaplasma spp., and Gardnerella vaginalis. In the meta-analysis (2947 women), Enterococcus spp. and Ureaplasma spp. were significantly more prevalent in women with CE, whereas Streptococcus spp., E. coli, Staphylococcus spp. and G. vaginalis showed non-significant trends. Only E. coli and Streptococcus spp. showed significant heterogeneity between-studies. Conclusions: CE is linked to microbial dysbiosis with reduced Lactobacillus dominance and enrichment of potentially pathogenic taxa, notably Enterococcus and Ureaplasma spp. These findings suggest that the endometrial microbiome contributes to chronic inflammation and adverse reproductive outcomes, yet heterogeneity and limited evidence call for standardized diagnostics and robust trials before clinical implementation. Full article
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13 pages, 760 KB  
Article
Anti-β2GPI/HLA-DR Antibody, Chronic Endometritis, and Uterine Endometrial Microbiome in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study
by Hideto Yamada, Yosuke Ono, Hajime Ota, Yuta Kobayashi, Yoshiyuki Fukushi, Shinichiro Wada and Hisashi Arase
Microorganisms 2026, 14(3), 544; https://doi.org/10.3390/microorganisms14030544 - 27 Feb 2026
Viewed by 506
Abstract
Anti-β2GPI/HLA-DR antibody, chronic endometritis (CE), and endometrial dysbiosis are likely to be associated with the etiologies of recurrent pregnancy loss (RPL). This prospective cohort study aimed to investigate these new risk factors together with conventional causes for RPL, and to evaluate pregnancy outcomes [...] Read more.
Anti-β2GPI/HLA-DR antibody, chronic endometritis (CE), and endometrial dysbiosis are likely to be associated with the etiologies of recurrent pregnancy loss (RPL). This prospective cohort study aimed to investigate these new risk factors together with conventional causes for RPL, and to evaluate pregnancy outcomes in women individually treated. A total of 87 women with RPL underwent conventional assessment together with anti-β2GPI/HLA-DR antibody measurements, CD138 immunohistochemistry for CE, and 16S rRNA sequence analysis for endometrial microbiome. Women with anti-β2GPI/HLA-DR antibody, CE, and endometrial dysbiosis received low-dose aspirin and heparin, antibiotics, and probiotics, respectively. Pregnancy outcomes of the participants were assessed. Anti-β2GPI/HLA-DR antibody, CE, non-Lactobacillus-dominant microbiome (NLDM)-1 (Lactobacillus + Bifidobacterium < 80%), and NLDM-2 (Lactobacillus without iners + Bifidobacterium < 80%) were detected in 16 (18.4%), 22 (25.3%), 27 (31.0%), and 46 (52.8%) women, respectively. Based on conventional assessment, 65.5% of women with RPL were classified as unexplained etiology; however, the percentage reduced to 16.1% when these new tests were assessed together. All 9 pregnancies with anti-β2GPI/HLA-DR antibody, 13 (92.9%) of 14 pregnancies with CE, and 24 (92.3%) of 26 pregnancies with NLDM-2 resulted in live birth. Assessment of these new tests may be clinically useful for reducing the proportion of unexplained RPL, and for providing high live birth rates if women receive relevant treatments. Full article
(This article belongs to the Collection Feature Papers in Medical Microbiology)
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19 pages, 909 KB  
Review
Miscarriage and the Microbiome: Host Genetics, Immunity, and the Reproductive Tract Ecosystem
by Nektaria Zagorianakou, Stylianos Makrydimas, Efthalia Moustakli, Ioannis Mitrogiannis and George Makrydimas
Genes 2026, 17(3), 259; https://doi.org/10.3390/genes17030259 - 25 Feb 2026
Viewed by 450
Abstract
Background/Objectives: Pregnancy loss is a common and multifactorial complication of human reproduction, traditionally attributed to fetal chromosomal abnormalities, maternal anatomical and endocrine disorders, and immune dysfunction. Growing evidence now indicates that the maternal microbiome, particularly within the reproductive tract, plays a critical role [...] Read more.
Background/Objectives: Pregnancy loss is a common and multifactorial complication of human reproduction, traditionally attributed to fetal chromosomal abnormalities, maternal anatomical and endocrine disorders, and immune dysfunction. Growing evidence now indicates that the maternal microbiome, particularly within the reproductive tract, plays a critical role in implantation, placental development, and the maintenance of immune tolerance during early pregnancy. Importantly, the influence of the microbiome on miscarriage appears to be strongly modulated by host genetic background and immune regulation. Methods: This narrative review summarizes current evidence linking alterations in the vaginal, endometrial, placental, and gut microbiomes to miscarriage, with a specific focus on host genetics and immune–microbial interactions. Results: We discuss how genetic variation in innate and adaptive immune pathways, inflammatory signaling, and mucosal barrier function may shape host responses to microbial communities, thereby influencing susceptibility to PL. In addition, we highlight emerging data on microbiome-driven regulation of gene expression and epigenetic modifications in the endometrium and decidua, emphasizing the role of microbial metabolites in immune tolerance and placental function. Conclusions: By integrating findings from microbiome research, host genomics, immunology, and epigenetics, this review proposes a framework in which miscarriage is viewed as a consequence of disrupted host–microbe crosstalk rather than isolated pathology. Finally, we address key methodological challenges and outline future research directions aimed at advancing mechanistic understanding and translational applications. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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19 pages, 318 KB  
Review
A Dive into the Invisible: The Vaginal and Endometrial Microbiota in Gynecologic and Obstetric Disorders: A Narrative Review
by Giorgia Schettini, Emilio Pieri, Cristina Rizzo, Matteo Giorgi, Virginia Mancini, Nassir Habib, Ramon Rovira and Gabriele Centini
Life 2026, 16(2), 344; https://doi.org/10.3390/life16020344 - 17 Feb 2026
Viewed by 877
Abstract
The human microbiota is increasingly recognized as a key component of women’s reproductive health. This narrative review examines the vaginal, endometrial, and gut microbiota and their roles in the pathogenesis of gynecologic and obstetric disorders, aiming to integrate current evidence into a clinically [...] Read more.
The human microbiota is increasingly recognized as a key component of women’s reproductive health. This narrative review examines the vaginal, endometrial, and gut microbiota and their roles in the pathogenesis of gynecologic and obstetric disorders, aiming to integrate current evidence into a clinically relevant framework. We review intrinsic (genetic, hormonal, and immunological) and extrinsic (environmental, lifestyle, and pharmacological) factors shaping microbial composition, with particular focus on dysbiosis and the role of the gut estrobolome within the microbiome in estrogen metabolism. The review synthesizes data on microbiota alterations associated with endometriosis, adenomyosis, uterine fibroids, endometrial polyps and hyperplasia, gynecologic malignancies, pelvic inflammatory disease, bacterial vaginosis, infertility, and adverse obstetric outcomes, including preterm birth and fetal growth restriction. Methodological approaches used to characterize the reproductive tract microbiota, such as vaginal swabs, endometrial sampling, and fecal analysis, are critically discussed, together with limitations related to low-biomass environments and contamination risk. Evidence regarding therapeutic modulation of the microbiota, including antibiotics, probiotics, hormonal therapies, and emerging microbiota-based interventions, is summarized, alongside the impact of gynecologic surgery on microbial translocation and long-term microbial balance. Overall, the available literature supports an association between microbiota alterations and multiple reproductive conditions, although causality remains incompletely established. Further standardized and longitudinal studies are needed to clarify mechanisms and guide microbiota-informed diagnostic and therapeutic strategies. Full article
29 pages, 802 KB  
Review
Endometrial Microbiome and Reproductive Receptivity: Diverse Perspectives
by Galina Stoyancheva, Nikolina Mihaylova, Maria Gerginova and Ekaterina Krumova
Int. J. Mol. Sci. 2025, 26(21), 10796; https://doi.org/10.3390/ijms262110796 - 6 Nov 2025
Cited by 7 | Viewed by 3705
Abstract
The human endometrium, previously considered a sterile environment, is now recognized as a low-biomass but biologically active microbial niche critical to reproductive health. Advances in sequencing technologies, particularly shotgun metagenomics, have provided unprecedented insights into the taxonomic and functional complexity of the endometrial [...] Read more.
The human endometrium, previously considered a sterile environment, is now recognized as a low-biomass but biologically active microbial niche critical to reproductive health. Advances in sequencing technologies, particularly shotgun metagenomics, have provided unprecedented insights into the taxonomic and functional complexity of the endometrial microbiome. While 16S rRNA sequencing has delineated the distinction between Lactobacillus-dominant and non-dominant microbial communities, shotgun metagenomics has revealed additional diversity at the species and strain level, uncovering microbial signatures that remain undetected by amplicon-based approaches. Current evidence supports the association of Lactobacillus dominance with endometrial homeostasis and favorable reproductive outcomes. Dysbiosis, characterized by increased microbial diversity and enrichment of anaerobic taxa such as Gardnerella, Atopobium, Prevotella, and Streptococcus, is linked to chronic endometritis, implantation failure, and adverse IVF results. Beyond compositional differences, the endometrial microbiome interacts with the host through immunological, metabolic, and epigenetic mechanisms. These interactions modulate cytokine signaling, epithelial barrier integrity, and receptivity-associated gene expression, ultimately influencing embryo implantation. However, discrepancies between published studies reflect the lack of standardized protocols for sampling, DNA extraction, and bioinformatic analysis, as well as the inherent challenges of studying low-biomass environments. Factors such as geography, ethnicity, hormonal status, and antibiotic exposure further contribute to interindividual variability. Culturomics approaches complement sequencing by enabling the isolation of viable bacterial strains, offering perspectives for microbiome-based biotherapeutics. Emerging 3D endometrial models provide additional tools to dissect microbiome–host interactions under controlled conditions. Taken together, the growing body of data highlights the potential of endometrial microbiome profiling as a biomarker for reproductive success and as a target for personalized interventions. Future research should focus on integrating multi-omics approaches and functional analyses to establish causal relationships and translate findings into clinical practice. This review gives a new insight into current knowledge on the uterine microbiome and its impact on implantation success, analyzed through the lenses of microbiology, immunology, and oxidative stress. Full article
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14 pages, 550 KB  
Systematic Review
Gynecological Cancer Oncobiome Systematic Review
by Tomasz Łatkiewicz, Karolina Rasoul-Pelińska, Krzysztof Kułak, Rafał Tarkowski, Anna Kułak and Iwona Puzio
Cancers 2025, 17(19), 3227; https://doi.org/10.3390/cancers17193227 - 3 Oct 2025
Cited by 2 | Viewed by 1644
Abstract
Objective: The primary objective of this systematic review is to present current knowledge about the oncobiome of gynecological cancers. Methods: Our systematic review contains data about the oncobiome of uterine corpus cancer, ovarian cancer and cervical cancer. Articles about other gynecological [...] Read more.
Objective: The primary objective of this systematic review is to present current knowledge about the oncobiome of gynecological cancers. Methods: Our systematic review contains data about the oncobiome of uterine corpus cancer, ovarian cancer and cervical cancer. Articles about other gynecological cancers were excluded. Results: A total of 72 articles were included in our systematic review. In uterine corpus cancer, cervical cancer and ovarian cancer, representatives of bacteria, fungi, viruses and parasites can be found. The oncobiome of ovarian cancer is connected with the oncobiome of head and neck cancers. Our systematic review proved that the human papilloma virus is connected with ovarian and cervical cancer. Gut dysbiosis can be used as a marker of ovarian cancer. In cervical cancer, we found the difference between the microbiota of healthy patients and patients with cervical cancer. Methylobacter, Robignitomaculum, Klebsiella, Micromonospora and Microbispora have an impact on overall survival. The microbiome of uterine corpus cancer is more differentiated than in cancer-free samples. Chronic endometrial inflammation has an impact on endometrial microbiome. Discussion: Treatment of gynecological cancers is changing permanently. Chemotherapy, as a systematic treatment, is being left in the past. Modern methods of therapy are addressed to specific genes. In the past, researchers claimed that tumors are sterile. However, the newest research indicates that malignancies were found to have genetic fragments of pathogens, which can be used as vectors for medications or as markers for the detection of a specific malignancy. Three most common gynecological cancers are as follows: endometrial cancer, ovarian cancer and cervical cancer. Each of these has their specific microbiome, which can be used for oncological treatment. These discoveries create possibilities for new, efficient methods of treatment. This systematic review analyzes publications about the composition of the gynecological tumor microenvironment, correlation between microbiomes of different organs, the female reproductive tract and the microbiome of the female reproductive tract during malignancy. Moreover, we provide information on the influence of some pathogens on the treatment. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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10 pages, 1261 KB  
Article
Effects of Intra-uterine Ceftiofur on the Equine Uterine Microbiome
by Kalie F. Beckers, Chin-Chi Liu, Viviane C. L. Gomes, Christopher J. Schulz, Gary W. Childers, Carleigh E. Fedorka and Jenny L. Sones
Vet. Sci. 2025, 12(9), 837; https://doi.org/10.3390/vetsci12090837 - 30 Aug 2025
Cited by 1 | Viewed by 1668
Abstract
Antimicrobial therapy is a mainstay for treating reproductive diseases, including endometritis. Ceftiofur, a third-generation cephalosporin, is a common antibiotic used to treat equine bacterial endometritis. It is also routinely given empirically as an intra-uterine (IU) infusion in broodmare practice. We hypothesized that ceftiofur [...] Read more.
Antimicrobial therapy is a mainstay for treating reproductive diseases, including endometritis. Ceftiofur, a third-generation cephalosporin, is a common antibiotic used to treat equine bacterial endometritis. It is also routinely given empirically as an intra-uterine (IU) infusion in broodmare practice. We hypothesized that ceftiofur IU would disrupt the resident microbial community within the healthy uterus of mares. To test our hypothesis, eight university-owned mares were selected for characterization of the estrual uterine microbiome before and after IU ceftiofur. Double-guarded swabs of the estrual endometrium were taken before and 3 days after both IU saline and ceftiofur in a crossover design. Isolation of DNA from endometrial swabs was performed, followed by amplification of the V4 region of the 16S rRNA gene by Illumina Miseq sequencing to examine core bacterial communities present before and after ceftiofur. The uterine microbial composition of sham and ceftiofur-treated mares was not significantly different as measured by beta diversity. The only notable difference was a lower abundance of Christensenellaceae_R-7_group after ceftiofur (0.14 ± 1.05% vs. 2.89 ± 1.07% control; p = 0.0428). In conclusion, three-day treatment of ceftiofur did not change the microbial composition acutely within the mare uterus when sampled directly after treatment. Ceftiofur may have a long-term effect on the uterine microbiome, which may require sampling several weeks post treatment. In conclusion, ceftiofur does not change the healthy uterine microbiome acutely during estrus and but should still be used judiciously. Full article
(This article belongs to the Section Veterinary Reproduction and Obstetrics)
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13 pages, 301 KB  
Review
The Impact of Genital Infections on Women’s Fertility
by Sara Occhipinti, Carla Ettore, Giosuè Giordano Incognito, Chiara Gullotta, Dalila Incognito, Roberta Foti, Giuseppe Nunnari and Giuseppe Ettore
Acta Microbiol. Hell. 2025, 70(3), 33; https://doi.org/10.3390/amh70030033 - 7 Aug 2025
Cited by 2 | Viewed by 8712
Abstract
Sexually transmitted infections (STIs) are a significant global health concern, affecting millions of people worldwide, particularly sexually active adolescents and young adults. These infections, caused by various pathogens, including bacteria, viruses, parasites, and fungi, can have profound implications for women’s reproductive health and [...] Read more.
Sexually transmitted infections (STIs) are a significant global health concern, affecting millions of people worldwide, particularly sexually active adolescents and young adults. These infections, caused by various pathogens, including bacteria, viruses, parasites, and fungi, can have profound implications for women’s reproductive health and fertility. This review explores the role of vaginal and uterine infections in women’s infertility, focusing on the most common pathogens and their impact on reproductive outcomes. Bacterial infections, such as those caused by intracellular bacteria (Mycoplasma, Ureaplasma, and Chlamydia), Neisseria gonorrhoeae, and bacterial vaginosis, are among the most prevalent causes of infertility in women. Studies have shown that these infections can lead to pelvic inflammatory disease, tubal occlusion, and endometrial damage, all of which can impair fertility. Mycobacterium tuberculosis, in particular, is a significant cause of genital tuberculosis and infertility in high-incidence countries. Viral infections, such as Human papillomavirus (HPV) and Herpes simplex virus (HSV), can also affect women’s fertility. While the exact role of HPV in female infertility remains unclear, studies suggest that it may increase the risk of endometrial implantation issues and miscarriage. HSV may be associated with unexplained infertility. Parasitic infections, such as trichomoniasis and schistosomiasis, can directly impact the female reproductive system, leading to infertility, ectopic pregnancy, and other complications. Fungal infections, such as candidiasis, are common but rarely have serious outcomes related to fertility. The vaginal microbiome plays a crucial role in maintaining reproductive health, and alterations in the microbial balance can increase susceptibility to STIs and infertility. Probiotics have been proposed as a potential therapeutic strategy to restore the vaginal ecosystem and improve fertility outcomes, although further research is needed to establish their efficacy. In conclusion, vaginal and uterine infections contribute significantly to women’s infertility, with various pathogens affecting the reproductive system through different mechanisms. Early diagnosis, appropriate treatment, and preventive measures are essential to mitigate the impact of these infections on women’s reproductive health and fertility. Full article
14 pages, 593 KB  
Review
Hashimoto’s Thyroiditis and Female Fertility: Endocrine, Immune, and Microbiota Perspectives in Assisted Reproduction—A Narrative Review
by Emilia Cristina Popa, Laura Maghiar, Teodor Andrei Maghiar, Ilarie Brihan, Laura Monica Georgescu, Bianca Anamaria Toderaș, Liliana Sachelarie and Anca Huniadi
Biomedicines 2025, 13(6), 1495; https://doi.org/10.3390/biomedicines13061495 - 18 Jun 2025
Cited by 4 | Viewed by 6748
Abstract
Hashimoto’s thyroiditis is the most prevalent autoimmune thyroid disorder, and it disproportionately affects women of reproductive age. Its impact on fertility and assisted reproductive technologies [ART] has become an area of growing clinical interest. Thyroid autoimmunity can influence female reproductive health through multiple [...] Read more.
Hashimoto’s thyroiditis is the most prevalent autoimmune thyroid disorder, and it disproportionately affects women of reproductive age. Its impact on fertility and assisted reproductive technologies [ART] has become an area of growing clinical interest. Thyroid autoimmunity can influence female reproductive health through multiple interconnected mechanisms, including subtle thyroid hormone imbalances, reduced ovarian reserve, altered endometrial receptivity, and dysregulated immune responses. Subclinical hypothyroidism and the presence of anti-thyroid antibodies have been linked to increased miscarriage risk and reduced success rates in ART, particularly in intracytoplasmic sperm injection (ICSI) cycles. Although levothyroxine supplementation is widely used, its benefits in euthyroid women remain uncertain. Recent studies suggest that gut microbiota may modulate immune function and affect fertility outcomes among women with autoimmune thyroid conditions. This narrative review synthesizes findings from a broad literature base of over 40 peer-reviewed publications published between 2010 and 2025, with 30 of the most relevant and methodologically robust studies selected for detailed analysis. The review integrates clinical, endocrine, immunological, and microbiome-related perspectives. The evidence supports the need for personalized fertility management in women with Hashimoto’s thyroiditis and highlights directions for future research into immune and microbiota-targeted therapies. Full article
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10 pages, 212 KB  
Article
Microbiota of Cervical Canal in Nine Patients Diagnosed with Ectopic Pregnancy: Case Series
by Kinga Bednarek, Katarzyna Wszołek, Monika Szewc, Mirosława Gałęcka, Adrian Mruczyński, Alan Bruszewski, Marcin Wierzchowski, Maciej Wilczak and Karolina Chmaj-Wierzchowska
Life 2025, 15(6), 949; https://doi.org/10.3390/life15060949 - 12 Jun 2025
Viewed by 1036
Abstract
Dysbiosis, or an altered microbiota composition, has been implicated in chronic endometrial inflammation and recurrent implantation failure. Despite growing research on the relationship between the genital microbiome and reproductive health, few studies have examined its role in ectopic pregnancy. Therefore, our study focuses [...] Read more.
Dysbiosis, or an altered microbiota composition, has been implicated in chronic endometrial inflammation and recurrent implantation failure. Despite growing research on the relationship between the genital microbiome and reproductive health, few studies have examined its role in ectopic pregnancy. Therefore, our study focuses on the microbiota of the cervical canal in women diagnosed with an ectopic pregnancy. Material and methods: The study group consisted of nine women of a reproductive age who were hospitalized at the Department of Maternal and Child Health, Gynecology and Obstetrics, Clinical Hospital of the University of Poznań, between February and September 2023. In nine patients, an ectopic pregnancy was diagnosed based on a transvaginal ultrasound examination. The swabs were collected for quantitative microbiological culture (using Amies transport medium). The microbiological analyses involved quantitative culture on selected selective and differential media, following the Standard Operating Procedure developed by the Institute of Microecology. Results: A reduced Lactobacillus spp. count (≤5 × 107 CFU/mL) was observed in 78% of the patients participating in the study, including those that produce H2O2, i.e., with strong protective properties for the environment of the female reproductive tract. The molecular analyses revealed Ureaplasma spp. (U. parvum and U. urealyticum) in 33% of the samples (three patients). However, Chlamydia trachomatis and Mycoplasma genitalium were not detected in any of the analyzed samples. Conclusions: The ease of obtaining material and the minimally invasive nature of lower reproductive tract examinations may allow for the evaluation of microbiota imbalances, helping to identify individuals at an increased risk of reproductive complications. Full article
(This article belongs to the Section Microbiology)
14 pages, 804 KB  
Article
Gut Microbiota Dysbiosis in Endometriosis: A Potential Link to Inflammation and Disease Progression
by Alexandra Irma Gabriela Baușic, Francesca Scurtu, Andrei Manu, Daniela Roxana Matasariu and Elvira Brătilă
Int. J. Mol. Sci. 2025, 26(11), 5144; https://doi.org/10.3390/ijms26115144 - 27 May 2025
Cited by 9 | Viewed by 5023
Abstract
Endometriosis is a complex gynaecological disorder characterised by the presence of endometrial-like tissue outside the uterus, leading to chronic inflammation, pain, and infertility. Recent research suggests that gut microbiota may play a crucial role in the pathogenesis and progression of endometriosis by modulating [...] Read more.
Endometriosis is a complex gynaecological disorder characterised by the presence of endometrial-like tissue outside the uterus, leading to chronic inflammation, pain, and infertility. Recent research suggests that gut microbiota may play a crucial role in the pathogenesis and progression of endometriosis by modulating immune responses and oestrogen metabolism. This study investigates the intestinal microbiota composition in women with endometriosis and its potential as a disease diagnosis and severity biomarker. Stool samples from nine patients diagnosed with endometriosis were analysed using the GI Effects® Comprehensive Stool Profile test. The tests revealed significant dysbiosis, particularly an altered Firmicutes/Bacteroidetes ratio and increased levels of Bacteroidetes. Inflammatory markers, including β-glucuronidase and secretory IgA, were also elevated, suggesting a potential link between gut microbiota and systemic inflammation in endometriosis. While our findings align with previous studies, further research with larger cohorts is necessary to validate these observations. Understanding the role of the microbiome in endometriosis could open new avenues for noninvasive diagnostic tools in endometriosis and microbiota-targeted therapies. Full article
(This article belongs to the Special Issue Endometriosis: Focusing on Molecular and Cellular Research)
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28 pages, 758 KB  
Review
Microbiome–Maternal Tract Interactions in Women with Recurrent Implantation Failure
by Manish Kumar, Yang Yan, Luhan Jiang, Ching-Ho Sze, Suranga P. Kodithuwakku, William S. B. Yeung and Kai-Fai Lee
Microorganisms 2025, 13(4), 844; https://doi.org/10.3390/microorganisms13040844 - 7 Apr 2025
Cited by 4 | Viewed by 4886
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Medical Microbiology)
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19 pages, 1591 KB  
Review
The Gut–Endometrium Axis: Exploring the Role of Microbiome in the Pathogenesis and Treatment of Endometrial Cancer—A Narrative Review
by Beibei Zhang, Nur Fatin Nabilah Mohd Sahardi, Wen Di, Xiaoran Long and Mohamad Nasir Shafiee
Cancers 2025, 17(6), 1044; https://doi.org/10.3390/cancers17061044 - 20 Mar 2025
Cited by 12 | Viewed by 4596
Abstract
Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview [...] Read more.
Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview of the existing knowledge on the interactions between these microbial communities and their influence on EC. Methodology: A literature review was conducted using electronic databases including Google Scholar, Scopus, and PUBMED, covering the period from 2017 to 2024. The following keywords were used for the literature search: (1) gut microbiome and endometrial cancer, (2) endometrium microbiome and endometrial cancer, and (3) endometrial cancer and microbial dysbiosis. The selected articles were chosen based on inclusion and exclusion criteria. Scale for Assessment of Narrative Review Articles (SANRA) was used for evaluating and assessing the quality of articles. Results: The gut microbiome modulates systemic inflammation, immune responses, and estrogen metabolism, all of which are crucial factors in EC development. Dysbiosis is an imbalance in the composition of microbes that can cause chronic inflammation and hormonal imbalances, which can contribute to the EC. Similarly, the endometrial microbiome, while less extensively studied, has been implicated in EC through mechanisms involving local immune modulation and the production of harmful metabolites. Probiotics, prebiotics, fecal microbiota transplantation (FMT), and personalized microbiota-based therapies can be used as clinical interventions for EC management. This review emphasizes the need for further research to explore the gut–endometrium axis and its potential for innovative therapeutic approaches. Understanding these complex interactions will become a novel strategy to prevent and treat EC, ultimately enhancing patient outcomes. Full article
(This article belongs to the Section Cancer Pathophysiology)
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23 pages, 1132 KB  
Review
Endometrial Receptivity–Lessons from “Omics”
by Louie Ye and Evdokia Dimitriadis
Biomolecules 2025, 15(1), 106; https://doi.org/10.3390/biom15010106 - 11 Jan 2025
Cited by 19 | Viewed by 7920
Abstract
The window of implantation (WOI) is a critical phase of the menstrual cycle during which the endometrial lining becomes receptive and facilitates embryo implantation. Drawing on findings from various branches of “omics”, including genomics, epigenomics, transcriptomics, proteomics, lipidomics, metabolomics, and microbiomics, this narrative [...] Read more.
The window of implantation (WOI) is a critical phase of the menstrual cycle during which the endometrial lining becomes receptive and facilitates embryo implantation. Drawing on findings from various branches of “omics”, including genomics, epigenomics, transcriptomics, proteomics, lipidomics, metabolomics, and microbiomics, this narrative review aims to (1) discuss mechanistic insights on endometrial receptivity and its implication in infertility; (2) highlight advances in investigations for endometrial receptivity; and (3) discuss novel diagnostic and therapeutic strategies that may improve reproductive outcomes. Full article
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23 pages, 1189 KB  
Review
The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature
by Bernadett Balla, Anett Illés, Bálint Tobiás, Henriett Pikó, Artúr Beke, Miklós Sipos, Péter Lakatos and János P. Kósa
Int. J. Mol. Sci. 2024, 25(23), 13227; https://doi.org/10.3390/ijms252313227 - 9 Dec 2024
Cited by 28 | Viewed by 10598
Abstract
The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly [...] Read more.
The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with Lactobacillus spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A Lactobacillus-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced Lactobacilli as well as an increased diversity and abundance of pathogenic species (e.g., Gardnerella vaginalis or Prevotella spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Pregnancy Complications)
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