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Keywords = reproductive dysbiosis

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12 pages, 788 KiB  
Article
Gut Microbial Composition on Dienogest Therapy in Patients with Endometriosis
by Veronika Pronina, Pavel Denisov, Vera Muravieva, Alexey Skorobogatiy, Ksenia Zhigalova, Galina Chernukha, Gennady Sukhikh and Tatiana Priputnevich
Microbiol. Res. 2025, 16(8), 169; https://doi.org/10.3390/microbiolres16080169 - 1 Aug 2025
Viewed by 232
Abstract
Endometriosis is a chronic inflammatory condition affecting approximately 10% of women of reproductive age, characterized by pelvic pain, dysmenorrhea, and infertility. Emerging evidence suggests a potential link between gut microbiota dysbiosis and endometriosis pathogenesis, mediated through hormonal regulation, immune modulation, and systemic inflammation. [...] Read more.
Endometriosis is a chronic inflammatory condition affecting approximately 10% of women of reproductive age, characterized by pelvic pain, dysmenorrhea, and infertility. Emerging evidence suggests a potential link between gut microbiota dysbiosis and endometriosis pathogenesis, mediated through hormonal regulation, immune modulation, and systemic inflammation. Dienogest (DNG) is widely used for endometriosis management, but its effects on gut microbiota remain underexplored. This study investigates the impact of DNG on gut microbial composition in endometriosis patients, aiming to elucidate its therapeutic mechanisms beyond hormonal modulation. DNG therapy led to a significant reduction in the Bacillota/Bacteroidota ratio (p = 0.0421), driven by decreased Staphylococcus spp. (p = 0.0244) and increased commensal bacteria such as Lactobacillus spp. and Collinsella aerofaciens (p = 0.049). Species richness and alpha diversity indices showed a non-significant upward trend. Notably, C. aerofaciens, a butyrate producer linked to gut barrier integrity, was detected twice as frequently during therapy. The study also observed reductions in facultative anaerobes like Enterococcus spp. and a trend toward higher titers of beneficial Bacteroidota. This study provides the first evidence that DNG therapy modulates gut microbiota in endometriosis patients, favoring a composition associated with anti-inflammatory and barrier-protective effects. The observed shifts—reduced opportunistic pathogens and increased symbionts—suggest a novel mechanism for DNG’s efficacy, potentially involving the microbial regulation of estrogen metabolism and immune responses. Full article
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16 pages, 636 KiB  
Review
The Gut–Endometriosis Axis: Genetic Mechanisms and Public Health Implications
by Efthalia Moustakli, Nektaria Zagorianakou, Stylianos Makrydimas, Emmanouil D. Oikonomou, Andreas Miltiadous and George Makrydimas
Genes 2025, 16(8), 918; https://doi.org/10.3390/genes16080918 - 30 Jul 2025
Viewed by 491
Abstract
Background/Objectives: Endometriosis is a chronic, estrogen-driven gynecological disorder affecting approximately 10% of reproductive-aged women worldwide, with significant physical, psychosocial, and socioeconomic impacts. Recent research suggests a possible involvement of the gut microbiome in endometriosis disease mechanisms through immune manipulation, estrogen metabolism, and [...] Read more.
Background/Objectives: Endometriosis is a chronic, estrogen-driven gynecological disorder affecting approximately 10% of reproductive-aged women worldwide, with significant physical, psychosocial, and socioeconomic impacts. Recent research suggests a possible involvement of the gut microbiome in endometriosis disease mechanisms through immune manipulation, estrogen metabolism, and inflammatory networks. This narrative review aims to summarize current evidence on gut microbiota changes in endometriosis patients, explore the mechanisms by which gut dysbiosis contributes to disease progression, and examine epidemiological links between gastrointestinal health and endometriosis risk. Methods: A narrative review was conducted to synthesize available literature on the compositional changes in gut microbiota associated with endometriosis. The review also evaluated studies investigating potential mechanisms and epidemiological patterns connecting gut health with endometriosis development and severity. Results: Alterations in gut microbiota composition were observed in endometriosis patients, suggesting roles in immune dysregulation, estrogen metabolism, and inflammation. Potential gut-oriented interventions, including dietary changes, probiotics, and lifestyle modifications, emerged as promising management options. However, methodological variability and research gaps remain barriers to clinical translation. Conclusions: Integrating gut microbiome research into endometriosis management holds potential for improving early diagnosis, patient outcomes, and healthcare system sustainability. The study emphasizes the need for further research to address existing challenges and to develop public health strategies that incorporate microbiome-based interventions in population-level endometriosis care. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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15 pages, 1024 KiB  
Review
The Impact of Endocrine Disruptors on the Female Genital Tract Microbiome: A Narrative Review
by Efthalia Moustakli, Themos Grigoriadis, Anastasios Potiris, Eirini Drakaki, Athanasios Zikopoulos, Ismini Anagnostaki, Athanasios Zachariou, Ekaterini Domali, Peter Drakakis and Sofoklis Stavros
Life 2025, 15(8), 1177; https://doi.org/10.3390/life15081177 - 24 Jul 2025
Viewed by 260
Abstract
Background/Objectives: Endocrine disruptors (EDs) are xenobiotic chemicals that disrupt hormone signaling and homeostasis within the human body. Accumulative evidence proposes that EDs could affect systemic hormone balance and local microbial communities, including the female genital tract (FGT) microbiome. The FGT microbiome, and especially [...] Read more.
Background/Objectives: Endocrine disruptors (EDs) are xenobiotic chemicals that disrupt hormone signaling and homeostasis within the human body. Accumulative evidence proposes that EDs could affect systemic hormone balance and local microbial communities, including the female genital tract (FGT) microbiome. The FGT microbiome, and especially the vaginal microbiota, contributes significantly to reproductive health maintenance, defense against infection, and favorable pregnancy outcomes. Disruption of the delicate microbial environment is associated with conditions like bacterial vaginosis, infertility, and preterm birth. Methods: The present narrative review summarizes the existing literature on EDs’ potential for changing the FGT microbiome. We discuss EDs like bisphenol A (BPA), phthalates, and parabens and their potential for disrupting the FGT microbiome through ED-induced hormone perturbations, immune modulation, and epithelial barrier breach, which could lead to microbial dysbiosis. Results: Preliminary evidence suggests that ED exposure–microbial composition changes relationships; however, robust human evidence for EDs’ changes on the FGT microbiome remains scarce. Conclusions: Our review addresses major research gaps and suggests future directions for investigation, such as the necessity for longitudinal and mechanistic studies that combine microbiome, exposome, and endocrine parameters. The relationship between EDs and the FGT microbiome could be critical for enhancing women’s reproductive health and for steering regulatory policies on exposure to environmental chemicals. Full article
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26 pages, 2094 KiB  
Review
The Androbactome and the Gut Microbiota–Testis Axis: A Narrative Review of Emerging Insights into Male Fertility
by Aris Kaltsas, Ilias Giannakodimos, Eleftheria Markou, Marios Stavropoulos, Dimitrios Deligiannis, Zisis Kratiras and Michael Chrisofos
Int. J. Mol. Sci. 2025, 26(13), 6211; https://doi.org/10.3390/ijms26136211 - 27 Jun 2025
Viewed by 783
Abstract
Male infertility is an under-recognized global health burden. Accumulating evidence position the intestinal microbiota as a pivotal regulator of testicular function, underpinning the emerging gut microbiota–testis axis. This narrative review introduces the conceptual term “androbactome”, referring to gut microorganisms and microbial genes that [...] Read more.
Male infertility is an under-recognized global health burden. Accumulating evidence position the intestinal microbiota as a pivotal regulator of testicular function, underpinning the emerging gut microbiota–testis axis. This narrative review introduces the conceptual term “androbactome”, referring to gut microorganisms and microbial genes that are hypothesized to influence androgen biosynthesis, spermatogenesis, and broader reproductive endocrinology. The documented worldwide decline in sperm concentration heightens the urgency of clarifying microbe-mediated influences on male reproductive capacity. The synthesis of preclinical and clinical findings reveals four principal pathways by which dysbiosis compromises fertility: systemic inflammation, oxidative stress, endocrine disruption, and epigenetic alteration. Lipopolysaccharide-driven cytokinaemia, reactive oxygen species generation, hypothalamic–pituitary–gonadal axis suppression, and aberrant germ cell methylation collectively impair sperm quality and hormonal balance. Short-chain fatty acids, secondary bile acids, and indole derivatives emerge as pivotal messengers within this crosstalk. Therapeutic approaches targeting the androbactome, namely dietary optimization, probiotic or prebiotic supplementation, and fecal microbiota transplantation, have demonstrated encouraging improvements in sperm parameters and testosterone levels, yet the causal inference is constrained by predominantly cross-sectional designs and limited long-term safety data. Recognizing the androbactome as a modifiable determinant of male fertility may open new avenues for personalized diagnosis, risk stratification, and adjunctive therapy in regard to idiopathic infertility. The integration of multi-omics platforms to characterize microbial and metabolomic signatures promises to enrich diagnostic algorithms and guide precision interventions, but rigorously controlled longitudinal and interventional studies are required to secure a translational impact. Full article
(This article belongs to the Special Issue Advanced Research of Gut Microbiota and Toxins)
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22 pages, 4716 KiB  
Article
Therapeutic Benefits of Nano-Echinacea Extract on Reproductive Injury Induced by Polystyrene Plastic Materials in Rat Model via Regulating Gut–Brain Axis
by Yi-Yuh Hwang, Sabri Sudirman, Pei-Xuan Tsai, Chine-Feng Mao, Athira Johnson, Tai-Yuan Chen, Deng-Fwu Hwang and Zwe-Ling Kong
Int. J. Mol. Sci. 2025, 26(13), 6097; https://doi.org/10.3390/ijms26136097 - 25 Jun 2025
Viewed by 499
Abstract
Plastics pollution is a critical global environmental issue, with growing concern over the increasing presence of nanoplastic particles. Plastics are major environmental pollutants that adversely affect human health, particularly when plastics from food sources enter the body and pose potential risks to reproductive [...] Read more.
Plastics pollution is a critical global environmental issue, with growing concern over the increasing presence of nanoplastic particles. Plastics are major environmental pollutants that adversely affect human health, particularly when plastics from food sources enter the body and pose potential risks to reproductive health. Echinacea purpurea is an immunologically active medicinal plant containing phenolic acids and alkylamides. Nanoparticles present a promising approach to enhance the effectiveness, stability, and bioavailability of Echinacea purpurea ethanol extract (EE) active components. This study aimed to determine the protective effects of chitosan-silica-Echinacea purpurea nanoparticles (CSE) against reproductive injury induced by polystyrene nanoplastics (PS-NPs) in male rats. The results showed that CSE dose-dependently reduced oxidative damage and protected intestinal and reproductive health. Furthermore, CSE improved gut microbiota dysbiosis, preserved barrier integrity, and attenuated PS-NPs-induced inflammation in the colon, brain, and gonads. Inflammatory factors released from the gut can enter the bloodstream, cross the blood–brain barrier, and potentially modulate the hypothalamic–pituitary–gonadal (HPG) axis. CSE has also been shown to elevate neurotransmitter levels in the colon and brain, thereby repairing HPG axis dysregulation caused by PS-NPs through gut–brain communication and improving reproductive dysfunction. This study enhances our understanding of CSE in modulating the gut–brain and HPG axes under PS-NPs-induced damage. CSE demonstrates the capacity to provide protection and facilitate recovery by mitigating oxidative stress and inflammation, restoring gut microbiota balance, and preserving hormone levels in the context of PS-NPs-induced injury. Full article
(This article belongs to the Section Molecular Pharmacology)
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10 pages, 212 KiB  
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 418
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)
15 pages, 1361 KiB  
Review
Gut Microbiome Dysbiosis and Its Impact on Reproductive Health: Mechanisms and Clinical Applications
by Efthalia Moustakli, Sofoklis Stavros, Periklis Katopodis, Anastasios Potiris, Peter Drakakis, Stefanos Dafopoulos, Athanasios Zachariou, Konstantinos Dafopoulos, Konstantinos Zikopoulos and Athanasios Zikopoulos
Metabolites 2025, 15(6), 390; https://doi.org/10.3390/metabo15060390 - 11 Jun 2025
Cited by 1 | Viewed by 964
Abstract
The human gut microbiome is integral to maintaining systemic physiological balance, with accumulating evidence emphasizing its critical role in reproductive health. This review investigates the bidirectional interactions between the gut microbiota and the female reproductive system, mediated by neuroendocrine, immune, and metabolic pathways, [...] Read more.
The human gut microbiome is integral to maintaining systemic physiological balance, with accumulating evidence emphasizing its critical role in reproductive health. This review investigates the bidirectional interactions between the gut microbiota and the female reproductive system, mediated by neuroendocrine, immune, and metabolic pathways, constituting the gut–reproductive axis. Dysbiosis, characterized by microbial imbalance, has been linked to reproductive disorders such as polycystic ovary syndrome (PCOS), endometriosis, infertility, impaired spermatogenesis, and pregnancy complications. These associations can be explained by immunological dysregulation, systemic inflammation, altered sex hormone metabolism, and hypothalamic–pituitary–gonadal (HPG) axis disturbances. This review aims to clarify the molecular and cellular mechanisms underpinning gut–reproductive interactions and to evaluate the feasibility of microbiome-targeted therapies as clinical interventions for improving reproductive outcomes. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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25 pages, 1138 KiB  
Review
Harnessing Microbiome, Bacterial Extracellular Vesicle, and Artificial Intelligence for Polycystic Ovary Syndrome Diagnosis and Management
by Bhawna Kushawaha, Tial T. Rem and Emanuele Pelosi
Biomolecules 2025, 15(6), 834; https://doi.org/10.3390/biom15060834 - 7 Jun 2025
Viewed by 992
Abstract
Polycystic ovary syndrome (PCOS) affects 6–19% of reproductive-age women worldwide, yet diagnosis remains challenging due to heterogeneous presentations and symptoms overlapping with other endocrine disorders. Recent studies have shown that gut dysbiosis plays a significant role in PCOS pathophysiology, with bacterial extracellular vesicles [...] Read more.
Polycystic ovary syndrome (PCOS) affects 6–19% of reproductive-age women worldwide, yet diagnosis remains challenging due to heterogeneous presentations and symptoms overlapping with other endocrine disorders. Recent studies have shown that gut dysbiosis plays a significant role in PCOS pathophysiology, with bacterial extracellular vesicles (BEVs) functioning as critical mediators of the gut–ovary axis. BEVs carry distinct cargos in PCOS patients—including specific miRNAs and inflammatory proteins—and show promise for both diagnostic and therapeutic applications. Artificial intelligence (AI) is emerging as a promising significant tool in PCOS research due to improved diagnostic accuracy and the capability to analyze complex datasets combining microbiome, BEV, and clinical parameters. These integrated approaches have the potential to better address PCOS multifactorial nature, enabling improved phenotypic classification and personalized treatment strategies. This review examines recent advances in the last 25 years in microbiome, BEV, and AI applications in PCOS research using PubMed, Web of Science, and Scopus databases. We explore the diagnostic potential of the AI-driven analysis of microbiome and BEV profiles, and address ethical considerations including data privacy and algorithmic bias. As these technologies continue to evolve, they hold increasing potential for the improvement of PCOS diagnosis and management, including the development of safer, more precise, and effective interventions. Full article
(This article belongs to the Special Issue Molecular Aspects of Female Infertility)
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17 pages, 858 KiB  
Review
Behind-the-Scenes Actors in Fertility: A Comprehensive Review of the Female Reproductive Tract Microbiome and Its Clinical Relevance
by Anthi Papakonstantinou, Efthalia Moustakli, Anastasios Potiris, Athanasios Zikopoulos, Ermioni Tsarna, Chrysi Christodoulaki, Ioannis Tsakiridis, Themistoklis Dagklis, Periklis Panagopoulos, Peter Drakakis and Sofoklis Stavros
Life 2025, 15(6), 916; https://doi.org/10.3390/life15060916 - 5 Jun 2025
Cited by 2 | Viewed by 725
Abstract
The study of the microbiome has rapidly progressed over the past few decades, capturing the interest of both scientists and the general public. Nevertheless, there is still no widely agreed-upon definition for the term “microbiome” despite tremendous advances in our knowledge. The international [...] Read more.
The study of the microbiome has rapidly progressed over the past few decades, capturing the interest of both scientists and the general public. Nevertheless, there is still no widely agreed-upon definition for the term “microbiome” despite tremendous advances in our knowledge. The international scientific literature consistently underscores the difference between the human microbiome and human microbiota. Recent research has emphasized the importance of the female reproductive tract microbiome in fertility, impacting natural conception and assisted reproductive technologies (ARTs). This review explores the relationship between infertility and the microbiota of the female reproductive tract through a thorough evaluation of research papers and large-scale studies published up to 2024. The objective of this review is to critically assess current evidence on the role of the reproductive tract microbiome in female infertility and ART outcomes. Relevant papers were identified and analyzed through the electronic medical databases PubMed/MEDLINE and Scopus. A comprehensive synthesis of data from 36 original studies was performed, including observational, case–control, cohort, and randomized trials. By focusing on the vagina, cervix, and endometrium, this study offers a comprehensive overview of the microbiome throughout the female reproductive tract. RIF and poor reproductive outcomes are strongly linked to dysbiosis, which is characterized by a reduction in Lactobacillus species. Lactobacillus crispatus, in particular, plays a significant role in protecting against bacterial vaginosis and infertility. A thorough understanding of how the microbiome impacts fertility and the development of clinical strategies to improve reproductive outcomes requires standardized microbiome investigation techniques and larger, randomized trials that account for diverse patient characteristics. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
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13 pages, 235 KiB  
Review
Impact of the Female Genital Microbiota on Outcomes of Assisted Reproductive Techniques
by Zacharias Fasoulakis, Dimitrios Papageorgiou, Athanasios Papanikolaou, Marianna Chatziioannou, Ioakeim Sapantzoglou, Afroditi Pegkou, George Daskalakis and Panos Antsaklis
Biomedicines 2025, 13(6), 1332; https://doi.org/10.3390/biomedicines13061332 - 29 May 2025
Viewed by 597
Abstract
The female genital microbiota plays a critical role in reproductive health and has recently emerged as a key factor influencing the outcomes of Assisted Reproductive Techniques (ARTs). Beyond traditional concerns about vaginal dysbiosis and infections such as bacterial vaginosis or mycoses, recent evidence [...] Read more.
The female genital microbiota plays a critical role in reproductive health and has recently emerged as a key factor influencing the outcomes of Assisted Reproductive Techniques (ARTs). Beyond traditional concerns about vaginal dysbiosis and infections such as bacterial vaginosis or mycoses, recent evidence highlights the broader impact of genital microbial communities, including the vaginal, cervical, and endometrial niches, on ART success rates. New findings suggest that specific bacterial profiles, as well as shifts in the virome and mycobiome, can significantly affect implantation and pregnancy outcomes. Non-invasive biomarkers such as menstrual blood have also been proposed for assessing endometrial receptivity. Furthermore, growing attention has been directed towards methodological challenges such as contamination risks during microbiota sampling which may influence study reliability. This review synthesizes the latest data on the relationship between the female genital microbiota and ART outcomes, with a focus on standardized microbiological analysis techniques and specific patient populations such as those experiencing recurrent implantation to optimize ART success based on microbiota profiling. Full article
(This article belongs to the Special Issue The Art of ART (Assisted Reproductive Technologies))
27 pages, 980 KiB  
Review
The Role of the Gut Microbiota in Female Reproductive and Gynecological Health: Insights into Endometrial Signaling Pathways
by Patricia Escorcia Mora, Diana Valbuena and Antonio Diez-Juan
Life 2025, 15(5), 762; https://doi.org/10.3390/life15050762 - 9 May 2025
Cited by 5 | Viewed by 2661
Abstract
Fertility is a dynamic, multifactorial process governed by hormonal, immune, metabolic, and environmental factors. Recent evidence highlights the gut microbiota as a key systemic regulator of reproductive health, with notable impacts on endometrial function, implantation, pregnancy maintenance, and the timing of birth. This [...] Read more.
Fertility is a dynamic, multifactorial process governed by hormonal, immune, metabolic, and environmental factors. Recent evidence highlights the gut microbiota as a key systemic regulator of reproductive health, with notable impacts on endometrial function, implantation, pregnancy maintenance, and the timing of birth. This review examines the gut–endometrial axis, focusing on how gut microbial communities influence reproductive biology through molecular signaling pathways. We discuss the modulatory roles of microbial-derived metabolites—including short-chain fatty acids, bile acids, and tryptophan catabolites—in shaping immune tolerance, estrogen metabolism, and epithelial integrity at the uterine interface. Emphasis is placed on shared mechanisms such as β-glucuronidase-mediated estrogen recycling, Toll-like receptor (TLR)-driven inflammation, Th17/Treg cell imbalance, and microbial translocation, which collectively implicate dysbiosis in the etiology of gynecological disorders including endometriosis, polycystic ovary syndrome (PCOS), recurrent implantation failure (RIF), preeclampsia (PE), and preterm birth (PTB). Although most current evidence remains correlational, emerging insights from metagenomic and metabolomic profiling, along with microbiota-depletion models and Mendelian randomization studies, underscore the biological significance of gut-reproductive crosstalk. By integrating concepts from microbiology, immunology, and reproductive molecular biology, this review offers a systems-level perspective on host–microbiota interactions in female fertility. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
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38 pages, 2063 KiB  
Review
The Multifactorial Pathogenesis of Endometriosis: A Narrative Review Integrating Hormonal, Immune, and Microbiome Aspects
by Zaure Datkhayeva, Ainur Iskakova, Alla Mireeva, Aida Seitaliyeva, Raikhan Skakova, Gulshat Kulniyazova, Aiman Shayakhmetova, Gaukhar Koshkimbayeva, Chapen Sarmuldayeva, Lazzat Nurseitova, Lyailya Koshenova, Gulzhan Imanbekova, Dina Maxutova, Sandugash Yerkenova, Aigerim Shukirbayeva, Ulzhan Pernebekova, Zaure Dushimova and Akerke Amirkhanova
Medicina 2025, 61(5), 811; https://doi.org/10.3390/medicina61050811 - 27 Apr 2025
Cited by 3 | Viewed by 1764
Abstract
Endometriosis (EM) is a common estrogen-dependent chronic inflammatory disorder affecting reproductive-aged women, yet its pathogenesis remains incompletely understood. Recent evidence suggests that the gut microbiota significantly influence immune responses, estrogen metabolism, and systemic inflammation, potentially contributing to EM progression. This narrative review explores [...] Read more.
Endometriosis (EM) is a common estrogen-dependent chronic inflammatory disorder affecting reproductive-aged women, yet its pathogenesis remains incompletely understood. Recent evidence suggests that the gut microbiota significantly influence immune responses, estrogen metabolism, and systemic inflammation, potentially contributing to EM progression. This narrative review explores the relationship between the gut microbiota and EM, emphasizing microbial dysbiosis, inflammation, estrogen regulation, and potential microbiome-targeted therapies. Studies published within the last 30 years were included, focusing on the microbiota composition, immune modulation, estrogen metabolism, and therapeutic interventions in EM. The selection criteria prioritized peer-reviewed articles, clinical trials, meta-analyses, and narrative reviews investigating the gut microbiota’s role in EM pathophysiology and treatment. Microbial dysbiosis in EM is characterized by a reduced abundance of beneficial bacteria (Lactobacillus, Bifidobacterium, and Ruminococcaceae) and an increased prevalence of pro-inflammatory taxa (Escherichia/Shigella, Streptococcus, and Bacteroides). The gut microbiota modulate estrogen metabolism via the estrobolome, contributing to increased systemic estrogen levels and lesion proliferation. Additionally, lipopolysaccharides (LPS) from Gram-negative bacteria activate the TLR4/NF-κB signaling pathway, exacerbating inflammation and EM symptoms. The interaction between the gut microbiota, immune dysregulation, and estrogen metabolism suggests a critical role in EM pathogenesis. While microbiota-targeted interventions offer potential therapeutic benefits, further large-scale, multi-center studies are needed to validate microbial biomarkers and optimize microbiome-based therapies for EM. Integrating microbiome research with precision medicine may enhance the diagnostic accuracy and improve the EM treatment efficacy. Full article
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13 pages, 510 KiB  
Review
The Role of the Genital Tract Microbiome in Human Fertility: A Literature Review
by Giuseppe Gullo, Marini’ Satullo, Valentina Billone, Lina De Paola, Stamatios Petousis, Yuliia Kotlik, Chrysoula Margioula-Siarkou, Antonio Perino and Gaspare Cucinella
J. Clin. Med. 2025, 14(9), 2923; https://doi.org/10.3390/jcm14092923 - 24 Apr 2025
Cited by 2 | Viewed by 2223
Abstract
Background/Objectives: Infertility is a multifactorial condition influenced by various factors, including dysbiosis and alterations in the genital tract microbiome. Recent studies emphasize the microbiome’s significant role in influencing a woman’s fertility potential, thereby affecting the chances of spontaneous conception and the outcomes [...] Read more.
Background/Objectives: Infertility is a multifactorial condition influenced by various factors, including dysbiosis and alterations in the genital tract microbiome. Recent studies emphasize the microbiome’s significant role in influencing a woman’s fertility potential, thereby affecting the chances of spontaneous conception and the outcomes of assisted reproductive treatments. Understanding the microbial characteristics and unique features of a healthy genital microbiome, as well as how changes in its composition can impact fertility, would allow for a more comprehensive and personalized approach to managing assisted reproductive treatments. The microbiome also influences pregnancy outcomes, and restoring its balance has been shown to improve fertility in infertile couples. The human microbiome plays a key role in maintaining the body’s overall health. Disruptions in microbiome balance among women of reproductive age can contribute to a range of pregnancy-related complications, with notable consequences for both maternal and fetal well-being. Emerging research has highlighted a connection between the reproductive tract microbiome and outcomes of assisted reproductive technologies (ART), suggesting that re-establishing a healthy microbial environment may enhance fertility in couples facing infertility. Methods: We conducted a search on PubMed using the keywords “microbiome”, “infertility”, and “ART” over the past 10 years. This article aims to provide an updated overview of the role of the microbiome in female reproductive health, with a focus on its implications for fertility treatment. Results: The microbiome has a significant role in influencing women’s fertility. Conclusions: Understanding the microbiome’s impact on fertility and pregnancy outcomes may lead to more effective and personalized approaches in fertility treatments, improving the chances of successful conception and pregnancy. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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28 pages, 758 KiB  
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
Viewed by 1494
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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20 pages, 1584 KiB  
Review
A Potential Link Between Oral Microbiota and Female Reproductive Health
by Justyna Marcickiewicz, Małgorzata Jamka and Jarosław Walkowiak
Microorganisms 2025, 13(3), 619; https://doi.org/10.3390/microorganisms13030619 - 7 Mar 2025
Cited by 1 | Viewed by 1539
Abstract
Oral cavity dysbiosis is associated with numerous inflammatory diseases, including diabetes, inflammatory bowel diseases, and periodontal disease. Changes in the oral microenvironment lead to bidirectional interactions between pathogens and individual host systems, which may induce systemic inflammation. There is increasing evidence linking the [...] Read more.
Oral cavity dysbiosis is associated with numerous inflammatory diseases, including diabetes, inflammatory bowel diseases, and periodontal disease. Changes in the oral microenvironment lead to bidirectional interactions between pathogens and individual host systems, which may induce systemic inflammation. There is increasing evidence linking the condition of the oral cavity with the most common causes of female infertility, such as polycystic ovary syndrome and endometriosis, as well as gestational complications, e.g., low birth weight, preterm delivery, and miscarriages. This review highlights the composition of the female oral microbiome in relation to infertility-related disorders, such as endometriosis and polycystic ovary syndrome, and provides a comprehensive overview of the current state of knowledge on the relationship between a dysbiotic oral microbiome, pregnancy, and its impact on the female reproductive tract. Full article
(This article belongs to the Section Medical Microbiology)
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