{"paper_id":"a2b3f3a0-887a-415e-bc6e-d3dedc176d39","body_text":"REVIEW | OPEN ACCESS   \n \nMedical Science 30, e9ms3757 (2026)                                                                                                                                                                       1 of 8 \n \n The role of the gut and \nreproductive tract microbiota in the \ndevelopment, diagnosis, and \ntreatment of endometriosis \n \nMalinowski M1 ⃰, Krasowski M2, Kalinowska A1, Pietras W1, \nKoziel A1, Kurek Z1, Jentkiewicz A1, Haj Obeid E1, Ulrych J1, \nKrupa J1 \n  \n \nABSTRACT \nEndometriosis is an inflammatory disorder. Caused by the proliferation of \nendometrial tissue outside the uterine mucosa. Progression results from elaborate \ninteractions among hormonal, immunological, and environmental factors. Growing \nevidence indicates that the gut and reproductive tract microbiota play a key role in \nthe pathogenesis of endometriosis. In patients with endometriosis, an increase in \npotentially pathogenic taxa, including Escherichia, Gardnerella, and Streptococcus, is \nobserved. Dysbiosis leads to the translocation of bacterial endotoxins \n(Lipopolysaccharide (LPS)), activation of the TLR4/NF -κB pathway, and increased \nproduction of pro -inflammatory cytokines (IL -6, IL -8, TNF -α), which promote \nangiogenesis and the proliferation of endometrial foci. Furthermore, disturbances in \nthe activity of the enzyme β -glucuronidase, part of the oestrobolome, increase the \npool of active oestrogens, playing a role in disease progression. Despite the growing \nnumber of studies, further prospective studies involving larger populations are \nneeded to standardise diagnostic methods and confirm the therapeutic potential of \nmicrobiome modulation in treating endometriosis. \n \nKeywords: endometriosis, gut microbiota, reproductive tract microbiota, \nestrabolome \n \n \n \n1. INTRODUCTION  \nEndometriosis is an inflammatory disease involving the growth of the uterine lining \noutside the uterus. Depending on the location, different names and forms of the \ndisease can be distinguished. Adenomyosis is a type of endometriosis located \nwithin the uterine wall. Superficial endometriosis is characterised by foci on the \nsurface of the peritoneum. Deep endometriosis is a condition in which endometrial \ncells grow beyond the female reproductive organs. A case of deep endometriosis \nhas even been described in which endometrial foci were in the central nervous \nsystem (Meggyesy et al., 2020). It most commonly affects young women of \nreproductive age, affecting 10% of women. \nMedical Science \n \nTo Cite: \nMalinowski M, Krasowski M, Kalinowska A, Pietras W, Koziel A, \nKurek Z, Jentkiewicz A, Haj Obeid E, Ulrych J, Krupa J. The role of the \ngut and reproductive tract microbiota in the development, diagnosis, \nand treatment of endometriosis. Medical Science 2026; 30: e9ms3757 \ndoi: https://doi.org/10.54905/disssi.v30i167.e9ms3757  \n \nAuthors’ Affiliation: \n1Medical University of Warsaw, 61 Żwirki i Wigury Street, 02-091 \nWarsaw, Poland \n2Poznań University of Medical Science, 10 Fredry Street, 61-701 \nPoznan, Poland \n \n⃰ Corresponding author: \nMaciej Malinowski, \nMedical University of Warsaw, 61 Żwirki i Wigury Street, 02-091 \nWarsaw, Poland \nE-mail: malinowskimaciej450@gmail.com \n \nContact List  \nMaciej Malinowski                   malinowskimaciej450@gmail.com \nMichał Krasowski                     mich.krasowski@wp.pl \nAlicja Kalinowska                     alusa.kalinowska@gmail.com \nWiktoria Pietras                        viktoriapietras01@gmail.com \nAdrian Koziel                            adriankoziel2001@gmail.com \nZofia Kurek                                kurekzofiaa@gmail.com \nAleksander Jentkiewicz           ajentkiewicz@gmail.com \nEsmail Haj Obeid      s082460@student.wum.edu.pl \nJakub Ulrych                              jakub.ulrych.rz@gmail.com \nJan Krupa                                   janeg.krupa@gmail.com \n \nOrcid List \nMaciej Malinowski                    0009-0003-7637-6290 \nMichał Krasowski                      0009-0006-6243-1246 \nAlicja Kalinowska                      0009-0000-9011-843X \nWiktoria Pietras                         0009-0003-2887-8755 \nAdrian Koziel                             0009-0006-6096-5850 \nZofia Kurek                                0009-0002-4156-8666 \nAleksander Jentkiewicz           0009-0008-4224-4069 \nEsmail Hai Obeid                      0009-0008-5165-1221 \nJakub Ulrych                              0009-0004-7460-965X  \nJan Krupa                                   0009-0001-2175-806X \n \nPeer-Review History \nReceived: 16 August 2025 \nReviewed & Revised: 25/August/2025 to 29/December/2025 \nAccepted: 07 January 2026 \nPublished: 21 January 2026 \n \nPeer-review Method \nExternal peer-review was done through double-blind method. \n \nMedical Science \npISSN 2321–7359; eISSN 2321–7367 \n \n \n© The Author(s) 2026. Open Access. This article is licensed under a Creative Commons \nAttribution License 4.0 (CC BY 4.0)., which permits use, sharing, adaptation, distribution and \nreproduction in any medium or format, as long as you give appropriate credit to the original \nauthor(s) and the source, provide a link to the Creative Commons license, and indicate if \nchanges were made. To view a copy of this license, visit \nhttp://creativecommons.org/licenses/by/4.0/. \n \n \n \n \n \n \nDISCOVERY \nSCIENTIFIC SOCIETY \n \n\n \nREVIEW | OPEN ACCESS   \n \nMedical Science 30, e9ms3757 (2026)                                                                                                                                                                       2 of 8 \nSampson's theory is the most popular among the existing theories (Konickx et al., 2019), which claims that in a new environme nt, \nretrograde menstrual blood flow may facilitate the transplantation and growth of endometrial fragments. This theory supports the \ntypical locations of endometriosis foci, such as the adnexal region, uterosacral ligaments, or the pouch of Douglas. Neverthe less, the \nanatomical obstruction to menstrual blood outflow or proven retrograde flow is not always associated with endometriosis. Risk  factors \ninclude: disturbances in menstrual blood flow, anatomical defects, prolonged oestrogen exposure, short menstrual cycles, low birth \nweight, or exposure to toxins (Konickx et al., 2019; Caporossi et al., 2021). Recently, increasing significance has been attr ibuted to the \nrole of dysbiosis in the gut and vaginal microbiota, which has the potential to amplify inflammation and disrupt hormonal bal ance \n(Molina et al., 2020).  \nAs endometrial implants shed just like the normal endometrium, they naturally correspond with the menstrual cycle. An intensified \ninflammatory process occurs, nerve-receptor transmission increases, and patients' perception of pain is heightened. This is the first and \nmost common symptom of endometriosis. What is more, the heavy menstrual bleeding and painful sexual intercourse (dyspareunia)  \noccur as well. In the long term, endometriosis can be a factor playing a role in an ectopic pregnancy, premature birth, or even infertility. \nThe well-established standard for its diagnosis is laparoscopy. The treatment for endometriosis includes pharmacological, surgical, an d \nwith supportive methods, depending on symptoms, the location of changes, and the patient's future reproductive plans. The \npharmacotherapy is mainly based on hormonal drugs. In refractory cases or deep infiltrating endometriosis, surgical treatment  (most \ncommonly laparoscopic) is used, aimed at removing the disease outbreaks. Supportive treatment includes physiotherapy, a specific diet \ntherapy, probiotic therapy, and psychological support.  \nCurrently, all treatment methods are symptomatic. Recently established treatment approaches include examining the gut and \nreproductive tract microbiota as potential targets for causal treatment. Nonetheless, the therapy should be individualised an d long-\nterm-oriented. Henceforth, the aim of this paper is to present the current state of research and knowledge on the role of the gut and \nreproductive tract microbiota in the pathogenesis and treatment of endometriosis, with particular emphasis on immunological, \nhormonal, and inflammatory mechanisms. \n \n \nFigure 1. Prisma Flowchart \n \n\n\n \nREVIEW | OPEN ACCESS   \n \nMedical Science 30, e9ms3757 (2026)                                                                                                                                                                       3 of 8 \n2. REVIEW METHODS  \nFor this review, we searched PubMed and Google Scholar for articles published. Electronic literature searches were performed with a \nrestriction to particular publication years (January , 1999 – July, 2025), using the following English search terms: endometriosis, gut \nmicrobiota, reproductive tract microbiota, oestrobolome. Inclusion criteria included literature treating clinical trials, systematic reviews, \nand original papers, as well as meta -analyses concerning the influence of the microbiome on the development of endometriosis, all \npublished in English. Exclusion criteria, however, included studies with weak methodology and publications written in languag es \nother than English (Figure 1). \n \n3. RESULTS & DISCUSSION \nRecent publications clearly indicate dysbiosis in the intestinal microbiota and reproductive organs. The disease develops as a result of \ncolonisation by pathogenic Escherichia, Gardnerella, Prevotella and a decrease in the number of protective Lactobacillus and Bifidobacterium \nbacteria. This disequilibrium promotes activation of the TLR4 and NF -kB pathways by LPS, leading to chronic inflammation. In turn, \nelevated concentrations of IL -6, IL -8, and TNF -alpha promote the growth of ectopic endometrial foci outside the uterine cavity. \nIncreased β -glucuronidase activity increases serum estrogen levels. Under the influence of estrogen, the endometrium undergoes \nincreased proliferation. In a short time, this can lead to clinical symptoms and exacerbation of the disease. The microbiome varies \ndepending on lesion stage and anatomical location, with some bacterial taxa exhibiting protective effects and others increasi ng disease \nrisk. Animal models have confirmed a causal link, as transplantation of microbiota from affected individuals induced endometr iotic \nlesions in healthy animals. Modulation of the microbiota, including increased levels of short -chain fatty acids (SCFAs), reduced lesion \ngrowth by influencing macrophage polarisation. The diversity of substances secreted by the microbiome and its composition ena bles \nthe development of diagnostic methods and screening tests in the future. To this end, diagnostics should be improved, and fun ding for \nclinical trials should be increased (Table 1).  \n \nTable 1: The impact of gut and reproductive tract microbiome on the development, diagnosis, and treatment of endometriosis. \nStudy Aspect Key findings Pathophysiological relevance \nHicks et al., 2025 Microbiota dysbiosis \nDecrease concentration: \nLactobacillus, Bifidobacterium \nIncrease concentration:   \nEscherichia, Prevotella, Gardnerella \nInduction of inflammation \nKhan et al., 2010 Inflammatory pathways ↑ LPS  \n↑ TLR4/NF-κB  Chronic inflammatory response \nMachado et al., 2022 \nWang et al., 2021 Inflammatory mediators \n↑ IL-6  \n↑ IL-8 \n↑ TNF-α \nProgression and persistence of \nendometriotic lesions \nKwa et al., 2016 Estrobolome ↑ β- glucuronidase  Increased levels of  estrogens \nJi et al., 2023 \nWang et al., 2025). Angiogenesis ↑ pro-angiogenic factors Vascularization and survival of \nectopic lesions \nQuaranta et al., 2019 \nLiu et al., 2024 Causal evidence Microbiota transplantation induces \nlesions (animal models) \nConfirms microbiota \ninvolvement \nLi et al., 2024 Microbiota modulation ↑ SCFAs-macrophage polarization Reduced lesion growth \nToffoli et al., 2025 Clinical potential Microbiome profiles as biomarkers  Targeted diagnosis and therapy \n \nCurrent State of Research and Knowledge  \nThe Physiological Role of the Gut Microbiome \nA description of the physiological role of the gut microbiome’s all functions is beyond the scope of this publication; nevert heless, to \nhighlight the enormous role it plays in our body, it is worth recalling that the number of cells making up the gut microflora  is several \ntimes greater than the number of cells in our body. We now know that its role goes beyond the digestive system as it includes  \ninfluences on the immune, hormonal, and nervous systems, as well as on the pathogenesis of gynaecological diseases such as \n\n \nREVIEW | OPEN ACCESS   \n \nMedical Science 30, e9ms3757 (2026)                                                                                                                                                                       4 of 8 \nendometriosis (Polycystic Ovary Syndrome – (PCOS)) and fertility disorders. It additionally plays an important role in the metabolism \nof nutrients and the production of (Short -Chain Fatty Acids (SCFA)). The compound exhibits anti -inflammatory properties by sealing \nthe intestinal membrane. It mobilises the immune system and activates dendritic cells, Th17 lymphocytes, and Treg cells (Li et al., 2024). \nDysbiosis then leads to excessive immune activation and a chronic inflammatory state, which ultimately promotes the developme nt of \ninflammatory, metabolic, autoimmune, and neoplastic diseases.  \n \nThe Physiological Role of the Female Reproductive Tract Microbiome \nThe microbiota of the female reproductive tract, notably of the vagina, is dominated under physiological conditions by bacter ia of the \nLactobacillus genus (L. crispatus, L. iners, L. gasseri, L. jensenii). They produce lactic acid, they maintain an acidic environment (pH < 4.5), \nwhich serves as protection for them from infections and a support for local mucosal immunity. A stable vaginal microbiome ser ves as a \nbarrier against pathogens while also ensuring immunological tolerance to natural bodily changes, such as during the menstrual cycle or \npregnancy. Disturbances in this state of balance result in dysbiosis. Most commonly referred to as bacterial vaginosis, it is  characterised \nby a decrease in Lactobacillus abundance and a predominance of anaerobic bacteria ( Gardnerella, Prevotella, Atopobium) (Wang et al., \n2021).  \nClinically, this is associated with increased susceptibility to reproductive and urinary tract infections. Modern sequencing \ntechniques have shown the presence of specific bacteria in the uterine cavity and peritoneal fluid (Chen et al., 2017). This has raised \nnew questions about their role in the initiation and progression of endometrial changes.  \nGut and genital dysbiosis can lead to the translocation of bacterial endotoxins (e.g., LPS), which activate the TLR4/NF -κB pathway. \nThe result is the production of pro -inflammatory cytokines (IL -6, IL -8, TNF -α), promoting angiogenesis and the proliferation of \nendometrial foci. Studies have long unravelled the differences in the composition of the gut, vaginal, and endometrial microb iota in \nwomen with endometriosis compared to healthy women. Among other findings, there was a decrease in beneficial (e.g., Lactobacillus \nand Bifidobacterium) and an increase in the proportion of potentially pathogenic bacteria (e.g. Escherichia, Streptococcus, Gardnerella). \nMore and more attention is being drawn to the increased prevalence of Phascolarctobacterium in patients' faeces, which serves as a \npossible diagnostic biomarker (Hicks et al., 2025). Initial attempts at microbiota modulation, probiotics, diet, antibiotics,  and, in animal \nmodels, faecal microbiota transplantation. Suggest that influencing the microbiome may reduce inflammation, limit the development of \nfoci, and relieve pain symptoms.  \n \nGut Microbiota and Endometriosis \nIn recent years, the gut microbiota has gained particular significance as a potential factor modulating the development and p rogression \nof endometriosis. A growing body of data indicates that its composition and functions can influence the immune response. The primary \nfactor associated with endometriosis development is increased intestinal permeability to pathogenic bacteria, which interfere s with the \nnormal microbiome. These disturbances lead to chronic inflammatory states, which are a risk factor for disease development. This leads \nto an accumulation of inflammatory cytokines (including TNF-α, IL-6, IL-8) and Vascular Growth Factors (VEGF).  \nAngiogenesis and inflammation enable the survival of endometrial implants in a new location. As early as 1999, Garcia -Velasco and \nArici conducted in vitro studies showing that IL -8 significantly increases the adhesion of cells to fibronectin, the main extracellular \nmatrix protein, in a dose -dependent manner, and further, the neutralisation of IL -8 with monoclonal antibodies partially blocked this \neffect, corroborating its important role in this process. The authors suggest that IL -8 is present in elevated concentrations. May function \nas an autocrine and paracrine factor, supporting the adhesion, proliferation, and angiogenesis of endometrial foci (1999), wh ich overall \ns that the peritoneal inflammatory microenvironment promotes the initiation of endometriosis, strengthening the early stages of \nendometrial cell implantation (Garcia-Velasco and Arici,1999). \nCurrently, there is no way to determine exactly what causes endometriosis. Many hypotheses have arisen on this topic, one of \nwhich is the bacterial contamination hypothesis. The authors demonstrated that (LPS) – the main component of the cell membrane of \nGram-negative bacteria, notably from Escherichia coli , can enter the peritoneal cavity with menstrual blood as a result of retrograde \nmenstruation. Studies have found that E. coli  contamination in the control group was larger. (LPS) activates the TLR4 and NF -kB \npathways, augmenting the inflammatory response. Active macrophages secrete TNF -alpha, IL -6, and IL -8. This process supports \nangiogenesis, followed by endometrial proliferation of ectopic endometrial lesions. Clinical studies have demonstrated gut dy sbiosis, \nand several taxa have been identified as more abundant in the study group, including the classes Bacilli, Clostridia, Coriobacteriia, and \nGammaproteobacteria (Ji et al., 2023; Wang et al., 2025). \n\n \nREVIEW | OPEN ACCESS   \n \nMedical Science 30, e9ms3757 (2026)                                                                                                                                                                       5 of 8 \nNevertheless, a change in the microbiome does not always favour disease development. Anaerotruncus, Olsenella, and \nRuminococcaceae may increase the risk of developing endometriosis, whereas Eubacterium ruminantium, Holdemania, and Sutterella have a \nprotective effect (Dang et al., 2024). The evidence of animal experiments supports this thesis (Chadchan et al., 2023), as it  has been \nproven that transplanting faecal microbiota from mice with endometriosis to healthy animals induces the development of lesions.  \nA correlation has been discovered between bacterial species and the location of endometriosis. Carriage of Blantia, Oscillospira, and \nAdlercreutzia increases the risk of ovarian and peritoneal disease (Tang et al., 2024). The microbiomes of female patients at different \nstages of disease progression were compared. Taxonomic analysis showed that in the early stage, bacteria such as Saccharofermentans, \nPrevotella, or Bacteroides predominated; however, in the late stage, Bartonella and Snodgrassella were the ones to show greater abundance. \nAs a result of the findings overall, Prevotella ruminicola and Bacteroides caecimuris were associated with a milder clinical course (Xu et al., \n2025; Cai et al., 2025).  \nA study including 38 patients with endometriosis and 20 healthy women was conducted, focusing on assessing levels of Mannose -\nBinding Lectin (MBL), the activity of the lectin pathway (LP), and associated changes in the endometrial microbiota. The auth ors \ndemonstrated that elevated plasma (MBL) levels correlate with disease advancement, but they were not linked to polymorphisms in \nthe MBL2 gene. Patients with elevated LPS concentrations were more likely to be carriers of pathogenic Gardnerella and Prevot ella \nbacteria (Wang et al., 2025). However, Lactobacillus significantly reduced LPS concentration. This was noted by the team (Tof foli et al., \n2025) in their study. They suggest that LPS may serve as a marker of disease progression in the future. They noted that this requires \nfurther research. \nSome substances secreted by bacteria have protective properties, e.g., SCFA. It alleviates inflammation and reduces disease \nsymptoms (Su et al., 2024). Faecal microbiota transplantation (FMT), from healthy donors increases SCFA concentration. This r esults in \nthe activation of the tyrosine kinases JAK1/STAT3 pathway within the lesions. The consequence of this was the polarisation of  \nmacrophages towards the M1 phenotype (Quaranta et al., 2019; Liu et al., 2024). \nThe oestrobolome is a term introduced by Plottel and Blaser in 2011, defining the set of bacterial genes in the gut microbiot a whose \nenzymatic products participate in oestrogen metabolism. The key enzyme in this process is β -glucuronidase, produced by bacterial \nspecies (e.g., Escherichia coli, Bacteroides, Clostridium). Oestrogens are metabolised and conjugated with glucuronic or sulphuric acid in \nthe liver. Next, it is then excreted with bile into the intestines. In the intestine, bacteria producing β -glucuronidase can break down \nconjugated oestrogens. Restoring their active form. Active oestrogens are reabsorbed into the circulation (enterohepatic circ ulation). \nRegular oestrobolome activity facilitates the maintenance of the appropriate level of oestrogens in the body, as shown in stu dies (Kwa \net al., 2016), and disturbances in this process can appear as hypooestrogenaemia or hyperoestrogenaemia. The latter can also directly \ninfluence endometrial growth in other locations or the development of oestrogen-dependent tumours (Hu et al., 2023). \nPlottel and Blaser analysed faecal and urine samples from 51 patients (27 with endometriosis, 24 healthy). In the faeces of p atients \nwith endometriosis, elevated levels of oestrogen metabolites were found: oestriol, 16 -epioestriol, 16α -hydroxyoestrone, and 2 -\nmethoxyoestradiol. On the contrary, such differences were not observed in urine samples. The authors emphasise that despite t he lack \nof clear signs of gut dysbiosis, the altered microbiota composition and increased concentrations of active oestrogen metaboli tes in \nfaeces may indicate subtle interactions between the gut microbiome and the oestrobolome in the pathogenesis of endometriosis.  This \nevidence shows a role for the microbiota in locally modulating oestrogen metabolism, which may further support disease development. \nThis data support the hypothesis that the gut oestrobolome can truly impact the pool of active oestrogens in the enterohepati c \ncirculation, consequently facilitating the progression of endometriosis (Pai et al., 2023). Studies on mouse models have conf irmed that \nadministration of β-glucuronidase causes an increase in LPS concentration and macrophage infiltration. This leads to an increase in the \ninflammatory response and disease progression (Wei et al., 2023). \n \nReproductive Tract Microbiota and Endometriosis \nFor a long time, it was believed that the cervical barrier provided adequate protection of the uterine cavity against colonis ation by \nmicroorganisms from the vagina and the external environment. However, thanks to advances in sequencing techniques and the \nexpansion of diagnostic methods. We know that the microflora of the reproductive tract consists of many species of bacteria ( Hugerth \net al., 2024). In patients with chronic endometritis, there was a significant decrease in the dominance of Lactobacillus bacteria in both the \nvagina and the uterus. What is essential is that transplanting vaginal microbiota from such patients into animal models resul ts in \nendometrial inflammation, a risk factor for endometriosis. A reverse trial was conducted, in which the introduction of the pr otective \nstrain Lactobacillus murinus showed an anti-inflammatory effect in animals. This way, a link was proven between infection of the lower \n\n \nREVIEW | OPEN ACCESS   \n \nMedical Science 30, e9ms3757 (2026)                                                                                                                                                                       6 of 8 \nreproductive tract, including the vagina, and an increased risk of endometriosis (Elizur et al., 2014). Female reproductive tract dysbiosis \nalso increases the risk of infertility, ectopic pregnancy, and endometrial cancer (Wessels et al., 2021). \nPatients are marked by decreased levels of Lactobacillus bacteria. This is typical for a healthy vaginal microbiome. In addition, there \nis colonisation by species that increase the risk of endometriosis: Gardnerella, Atopobium, Prevotella, or Megasphaera (Sessa et al., 2024). In \npatients with endometriosis, Escherichia coli was more frequently detected in menstrual blood and endometrial smears, a findi ng that \nis significant given the presence of LPS bacterial endotoxins capable of activating TLR4 receptors and intensifying local inf lammatory \nreactions (Khan et al., 2010). Higher levels of endotoxins and (Heat Shock Proteins (HSP70)) were found in the menstrual and \nperitoneal fluid of patients with endometriosis, which increases the chances of survival and proliferation of endometrial cel ls via the \nTLR4 signalling pathway (Khan et al., 2013). \nDue to diagnostic difficulties and the lack of a specific disease marker, considerable funding has been allocated to research  on this \ntopic, resulting in the creation of a specialised predictive model. The algorithm created enables differentiation between the  microbiome \nof the vagina and the reproductive tract in sick and healthy patients with an accuracy of 81% sensitivity and 88% specificity (MacSharry \net al., 2024). The significance of the microbiome in the pathogenesis of endometriosis is also supported by studies examining  its \ncomposition in sick patients. Specific patterns of IgG glycosylation in serum and urine may be another marker of the disease \n(MacSharry et al., 2024; Li et al., 2025). Currently, however, the tests have not found any clinical application due to high diagnostic costs \nand the complexity of the process.  \nThe inoculation with Fusobacterium in animal models resulted in exacerbation of endometriosis, whereas antibiotic treatment \nsignificantly decreased the number and mass of disease foci (Muraoka et al., 2023). Due to the lack of causal treatment, howe ver, much \nattention is devoted to new methods and hopes for the future are placed in probiotics.  \nProgress in observations indicates a high therapeutic potential targeted at the microbiome Lactobacillus spp , as the dominant \ncomponent of healthy vaginal flora, not only strengthens the mucosal barrier but also limits the colonisation of pathogens (e .g., \nGardnerella vaginalis , E. coli), consequently lowering the production of pro -inflammatory cytokines (IL -6, IL -8, TNF -α). It inhibits the \naction of endotoxins, which is notably important in treatment (Machado et al., 2022; Wang et al., 2021). Given current eviden ce, the \nfemale reproductive tract microbiome is no longer associated solely with infections requiring antibiotic treatment; it is now  a source of \nknowledge for future diagnostic and therapeutic methods. \n \n4. CONCLUSION \nMore and more studies indicate that dysbiosis promotes the development of the disease. Both intestinal and reproductive tract  \nmicrobiome disorders promote the progression of endometriosis through particular mechanisms. Activation of TLR4 receptors by LPS \nmolecules and the subsequent activation of the NF -κB inflammatory pathway lead to the proliferation of ectopic endometrial foci. An \nadditional influence is the increased concentration of estrogens, which is affected by the estrobolome. Currently, pathogenic  and \nprotective bacteria have been identified. In the future, this division may allow for greater precision and earlier diagnosis of patients. \nAnimal studies indicate that disruption of the microbiota may influence the development or inhibition of disease lesions. Res earchers \nemphasise the future therapeutic impact of disease regression in animals. \nThe studies describe molecules secreted by bacteria that may have the potential to alleviate the development of the disorder.  SCFAs \nhave immunomodulatory effects, reduce inflammation, and limit the activation of immune system cells. Their low concentration \ncorrelated with the development of endometriosis. Promising results and evidence from animal models deliver a meaningful \nunderstanding of future diagnostic and clinical therapies. However, further research is required to completely understand the se \nrelationships and their potential clinical applications. \n \nAcknowledgments \nThe authors have no acknowledgments to disclose. \n \nInformed consent \nNot applicable. \n \nEthical approval \nNot applicable. This article does not contain any studies with human participants or animals performed by any of the authors. \n\n \nREVIEW | OPEN ACCESS   \n \nMedical Science 30, e9ms3757 (2026)                                                                                                                                                                       7 of 8 \nFunding \nThis research did not receive any external funding like specific grant from funding agencies in the public, commercial, or nonprofit \nsectors. \n \nConflict of interest \nThe authors declare that they have no conflicts of interests, competing financial interests or personal relationships that could have \ninfluenced the work reported in this paper. \n \nData and materials availability \nAll data associated with this study will be available based on reasonable request to the Corresponding Author. \n \nREFERENCES \n1. Cai Z, Zhou Z, Huang S, Ma S, Chen Y, Cao Y, Ma Y. Gut \nmicrobiome in patients with early -stage and late -stage \nendometriosis. BMC Women’s Health 2025; 25(1):163. doi:  \n10.1186/s12905-025-03689-0.  \n2. Caporossi L, Capanna S, Viganò P, Alteri A, Papaleo B. From \nEnvironmental to Possible Occupational Exposure to Risk \nFactors: What Role Do They Play in the Aetiology of \nEndometriosis? Int J Environ Res Public Health 2021; 18(2):  \n532. doi:10.3390/ijerph18020532. \n3. Chadchan SB, Naik SK, Popli P, Talwar C, Putluri S, Ambati \nCR, Lint MA, Kau AL, Stallings CL, Kommagani R. Gut \nmicrobiota and microbiota -derived metabolites promote \nendometriosis. Cell Death Discov 2023; 9(1):28. doi:10.1038/  \ns41420-023-01309-0.  \n4. Chen C, Song X, Wei W, Zhong H, Dai J, Lan Z, Li F, Yu X, \nFeng Q, Wang Z, Xie H, Chen X, Zeng C, Wen B, Zeng L, Du \nH, Tang H, Xu C, Xia Y, Xia H, Yang H, Wang J, Wang J, \nMadsen L, Brix S, Kristiansen K, Xu X, Li J, Wu R, Jia H. The \nmicrobiota continuum along the female reproductive tract and \nits relation to uterine -related diseases. Nat Commun 2017; \n8(1):875. doi:10.1038/s41467-017-00901-0.  \n5. Dang C, Chen Z, Chai Y, Liu P, Yu X, Liu Y, Liu J. Assessing \nthe relationship between gut microbiota and endometriosis: a \nbidirectional two -sample mendelian randomisation analysis. \nBMC Women’s Health 2024; 24(1):123. doi:10.1186/s12905 -024-\n02945-z. \n6. Elizur SE, Lebovitz O, Weintraub AY, Eisenberg VH, Seidman \nDS, Goldenberg M, Soriano D. Pelvic inflammatory disease in \nwomen with endometriosis is more severe than in those \nwithout. Aust N Z J Obstet Gynaecol 2014; 54(2):162 -5. doi:  \n10.1111/ajo.12189.  \n7. Garcia-Velasco JA, Arici A. Interleukin -8 stimulates the \nadhesion of endometrial stromal cells to fibronectin. Fertil \nSteril 1999; 72(2):336-40. doi:10.1016/s0015-0282(99)00223-x.  \n8. Hicks C, Leonardi M, Chua XY, Mari -Breedt L, Espada M, El -\nOmar EM, Condous G, El -Assaad F. Oral, Vaginal, and Stool \nMicrobial Signatures in Patients With Endometriosis as \nPotential Diagnostic Non -Invasive Biomarkers: A Prospective \nCohort Study. BJOG 2025; 132(3):326-336. doi:10.1111/1471-052 \n8.17979. \n9. Hu S, Ding Q, Zhang W, Kang M, Ma J, Zhao L. Gut microbial \nbeta-glucuronidase: a vital regulator in female estrogen \nmetabolism. Gut Microbes 2023; 15(1):2236749. doi:10.1080/19  \n490976.2023.2236749.  \n10. Hugerth LW, Krog MC, Vomstein K, Du J, Bashir Z, \nKaldhusdal V, Fransson E, Engstrand L, Nielsen HS, Schuppe-\nKoistinen I. Defining Vaginal Community Dynamics: daily \nmicrobiome transitions, the role of menstruation, \nbacteriophages, and bacterial genes. Microbiome 2024; 12(1):  \n153. doi:10.1186/s40168-024-01870-5.  \n11. Ji X, Yang Q, Zhu XL, Xu L, Guo JY, Rong Y, Cai YL. \nAssociation between gut microbiota and endometriosis: a \ntwo-sample Mendelian randomisation study. Front Microbiol \n2023; 14:1188458. doi:10.3389/fmicb.2023.1188458.  \n12. Khan KN, Kitajima M, Hiraki K, Yamaguchi N, Katamine S, \nMatsuyama T, Nakashima M, Fujishita A, Ishimaru T, \nMasuzaki H. Escherichia coli contamination of menstrual \nblood and effect of bacterial endotoxin on endometriosis. \nFertil Steril 2010; 94(7):2860-3.e1-3. doi:10.1016/j.fertnstert.2010 \n.04.053.  \n13. Khan KN, Kitajima M, Inoue T, Tateishi S, Fujishita A, \nNakashima M, Masuzaki H. Additive effects of inflammation \nand stress reaction on Toll -like receptor 4-mediated growth of \nendometriotic stromal cells. Hum Reprod 2013; 28(10):2794 -\n803. doi:10.1093/humrep/det280.  \n14. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, \nMartin DC. Pathogenesis of endometriosis: the genetic/  \nepigenetic theory. Fertil Steril 2019; 111(2):327 -340. doi: \n10.1016/j.fertnstert.2018.10.013.  \n15. Kwa M, Plottel CS, Blaser MJ, Adams S. The Intestinal \nMicrobiome and Estrogen Receptor -Positive Female Breast \n\n \nREVIEW | OPEN ACCESS   \n \nMedical Science 30, e9ms3757 (2026)                                                                                                                                                                       8 of 8 \nCancer. J Natl Cancer Inst 2016; 108(8):djw029. doi:10.1093/  \njnci/djw029. \n16. Li C, Xu X, Zhao X, Du B. The inconsistent pathogenesis of \nendometriosis and adenomyosis: insights from endometrial \nmetabolome and microbiome. mSystems 2025; 10(5):e0020225. \ndoi:10.1128/msystems.00202-25.  \n17. Li Z, Xiong W, Liang Z, Wang J, Zeng Z, Kołat D, Li X, Zhou \nD, Xu X, Zhao L. Critical role of the gut microbiota in immune \nresponses and cancer immunotherapy. J Hematol Oncol 2024; \n17(1):33. doi:10.1186/s13045-024-01541-w.  \n18. Liu M, Peng R, Tian C, Shi J, Ma J, Shi R, Qi X, Zhao R, Guan \nH. Effects of the gut microbiota and its metabolite short -chain \nfatty acids on endometriosis. Front Cell Infect Microbiol 2024; \n14:1373004. doi:10.3389/fcimb. 2024.1373004.  \n19. Machado A, Foschi C, Marangoni A. Editorial: Vaginal \ndysbiosis and biofilms. Front Cell Infect Microbiol 2022; \n12:976057. doi:10.3389/fcimb.2022.976057.  \n20. MacSharry J, Kovács Z, Xie Y, Adamczyk B, Walsh C, Reidy F, \nMcAuliffe FM, Kilbane MT, Twomey PJ, Rudd PM, Wingfield \nM, Butler M, van Sinderen D, Glover L, Saldova R. \nEndometriosis specific vaginal microbiota links to urine and \nserum N -glycome. Sci Rep 2024; 14(1):25372. doi:10.1038/  \ns41598-024-76125-2.  \n21. Meggyesy M, Friese M, Gottschalk J, Kehler U. Case Report of \nCerebellar Endometriosis. J Neurol Surg A Cent Eur \nNeurosurg 2020; 81(4):372-376. doi:10.1055/s-0040-1701622.  \n22. Molina NM, Sola-Leyva A, Saez-Lara MJ, Plaza-Diaz J, Tubić-\nPavlović A, Romero B, Clavero A, Mozas -Moreno J, Fontes J, \nAltmäe S. New Opportunities for Endometrial Health by \nModifying Uterine Microbial Composition: Present or Future? \nBiomolecules 2020; 10(4):593. doi: 10.3390/biom10040593.  \n23. Muraoka A, Suzuki M, Hamaguchi T, Watanabe S, Iijima K, \nMurofushi Y, Shinjo K, Osuka S, Hariyama Y, Ito M, Ohno K, \nKiyono T, Kyo S, Iwase A, Kikkawa F, Kajiyama H, Kondo Y. \nFusobacterium infection facilitates the development of \nendometriosis through the phenotypic transition of \nendometrial fibroblasts. Sci Transl Med 2023; 15(700): \neadd1531. doi:10.1126/scitranslmed.add1531.  \n24. Pai AH, Wang YW, Lu PC, Wu HM, Xu JL, Huang HY. Gut \nMicrobiome-Estrobolome Profile in Reproductive -Age \nWomen with Endometriosis. Int J Mol Sci 2023; 24(22):16301. \ndoi:10.3390/ijms242216301.  \n25. Quaranta G, Sanguinetti M, Masucci L. Faecal Microbiota \nTransplantation: A Potential Tool for Treatment of Human \nFemale Reproductive Tract Diseases. Front Immunol 2019; \n10:2653. doi:10.3389/fimmu. 2019.02653.  \n26. Sessa R, Filardo S, Viscardi MF, Brandolino G, Muzii L, Di \nPietro M, Porpora MG. Characterization of the vaginal \nmicrobiota in Italian women with endometriosis: preliminary \nstudy. Arch Gynecol Obstet 2024; 310(4):2141 -2151. doi:  \n10.1007/s00404-024-07631-x.  \n27. Su C, Wan S, Ding J, Ni G, Ding H. Blood lipids mediate the \neffects of gut microbiome on endometriosis: a mendelian \nrandomisation study. Lipids Health Dis 2024; 23(1):110. doi:  \n10.1186/s12944-024-02096-y.  \n28. Tang Y, Yang J, Hang F, Huang H, Jiang L. Unravelling the \nrelationship between gut microbiota and site -specific \nendometriosis: a Mendelian randomisation analysis. Front \nMicrobiol 2024; 15:1363080. doi:10.3389/fmicb.2024.1363080.  \n29. Toffoli M, Campisciano G, Santin A, Pegoraro S, Zito G, \nSpedicati B, Balduit A, Romano F, Di Lorenzo G, Mangogna \nA, Tesolin P, Nardone GG, Zanotta N, Sanna S, Crobu F, \nKishore U, Ricci G, Bulla R, Girotto G, Agostinis C. A possible \nassociation between low MBL/lectin pathway functionality \nand microbiota dysbiosis in endometriosis patients. Life Sci \n2025; 364:123427. doi:10.1016/j.lfs.2025.123427.  \n30. Wang J, Li Z, Ma X, Du L, Jia Z, Cui X, Yu L, Yang J, Xiao L, \nZhang B, Fan H, Zhao F. Translocation of vaginal microbiota \nis involved in impairment and protection of uterine health. \nNat Commun 2021; 12(1):4191. doi:10.1038/s41467 -021-24516-\n8.  \n31. Wang J, Li Z, Ma X, Du L, Jia Z, Cui X, Yu L, Yang J, Xiao L, \nZhang B, Fan H, Zhao F. Translocation of vaginal microbiota \nis involved in impairment and protection of uterine health. \nNat Commun 2021; 12(1):4191. doi:10.1038/s41467 -021-24516-\n8.  \n32. Wang M, Liu W, Zheng L, Ma S, Jin L, Zhao D, Li D. \nBroadening horizons: microbiota as a novel biomarker and \npotential treatment for endometriosis. Front Microbiol 2025; \n16:1521216. doi:10.3389/fmicb.2025.1521216.  \n33. Wei Y, Tan H, Yang R, Yang F, Liu D, Huang B, OuYang L, \nLei S, Wang Z, Jiang S, Cai H, Xie X, Yao S, Liang Y. Gut \ndysbiosis-derived β-glucuronidase promotes the development \nof endometriosis. Fertil Steril 2023; 120(3 Pt 2):682 -694. doi:  \n10.1016/j.fertnstert.2023.03.032.  \n34. Wessels JM, Domínguez MA, Leyland NA, Agarwal SK, \nFoster WG. Endometrial microbiota is more diverse in people \nwith endometriosis than symptomatic controls. Sci Rep 2021; \n11(1):18877. doi:10.1038/s41598-021-98380-3.  \n35. Xu Y, Zhu Y, Wu X, Peng W, Zhong Y, Cai Y, Chen W, Liu L, \nTan B, Chen T. Gut Microbiota -Derived Acetate Ameliorates \nEndometriosis via JAK1/STAT3 -Mediated M1 Macrophage \nPolarisation. Microb Biotechnol 2025; 18(8):e70202. doi:10.1111  \n/1751-7915.70202.","source_license":"CC0","license_restricted":false}