The Microbiota-Endometriosis Axis: An Immune-Endocrine Integration Model and Emerging Therapeutic Targets

Georgiana Nemeti, Anca Crăciun, Anca Elena Crăciun, Dan Claudiu Măgureanu, Florentina Claudia Militaru, Ioana Corina Bocsan, Cristian-Ioan Crăciun, Adriana Rusu, Carmen Stanca Melincovici, Anca Dana Buzoianu, Daniel Mureșan, Maria Adriana Neag, Maria Neag
International journal of molecular sciences · 2026 · vol. 27(11) , pp. 4883 · doi:10.3390/ijms27114883 · PMID:42278410 · PMC13257328 · W7163182908
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review proposes that the microbiota integrates immune-endocrine signaling in endometriosis, impacting disease through gut barrier integrity, inflammation, immune dysfunction, and estrogen metabolism, suggesting microbiome-based therapies.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-17 ⓘ

This narrative review integrates evidence on the microbiota–endometriosis axis, focusing on immune–endocrine mechanisms (e.g., gut microbial estrobolome activity affecting enterohepatic estrogen pools, immune dysfunction such as altered NK and macrophage phenotypes, and downstream inflammatory pathways) and summarizes current and emerging microbiota-targeted therapeutic concepts. It used a structured literature search of PubMed/MEDLINE, Scopus, and Web of Science through March 2026 and included original studies, systematic reviews, and meta-analyses, but it synthesizes data qualitatively and does not provide a quantitative analysis, acknowledging substantial heterogeneity across studies. The review proposes a unifying model in which microbiota-driven immune and endocrine interactions contribute to endometriosis heterogeneity, persistence, and variable treatment responses. This paper is centrally about endometriosis — it builds an immune–endocrine framework linking gut/reproductive microbiota to endometriosis pathogenesis and discusses microbiota-targeted interventions.

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Abstract

Endometriosis is a chronic, estrogen-dependent inflammatory disorder characterized by the ectopic implantation and persistence of endometrial-like tissue outside the uterine cavity. Despite its high prevalence and significant impact on quality of life, the pathogenesis of endometriosis remains incompletely understood and involves a complex interplay between hormonal dysregulation, immune dysfunction, and chronic inflammation. In recent years, growing evidence has highlighted the role of the microbiota as a potential modulator of these interconnected pathways. This review proposes an integrative framework in which the microbiota acts as a central modulator of immune-endocrine interactions in endometriosis, while synthesizing current evidence on underlying biological mechanisms. We discuss how alterations in the gut, vaginal, and endometrial microbiota contribute to disease pathophysiology through multiple mechanisms, including disruption of intestinal barrier integrity, activation of pro-inflammatory signaling pathways, immune dysregulation, and modulation of estrogen metabolism via the estrobolome. Microbial β-glucuronidase activity and enterohepatic recirculation of estrogens are explored as key processes linking gut dysbiosis to the hyperestrogenic environment characteristic of endometriosis. Furthermore, we review current pharmacological treatments and highlight their limitations, emphasizing the need for novel therapeutic strategies targeting upstream disease mechanisms. Emerging approaches, including probiotics, postbiotics, short-chain fatty acids, and dietary interventions, are discussed as promising adjunctive therapies capable of modulating inflammation, immune responses, and metabolic pathways. Although current evidence remains heterogeneous and largely derived from preclinical and observational studies, the microbiota emerges not only as a potential therapeutic target but as a key integrative node linking endocrine, immune, and metabolic pathways in endometriosis. Future research should focus on well-designed clinical trials to validate microbiome-based interventions and to define their role in personalized management strategies for endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Microbiota Microbiota Microbiota Microbiota Animals Animals Animals Animals Estrogens Estrogens Estrogens Estrogens

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (100)

SciLite annotations

chemicals 135
estrogen estrogen oxygen iron lipid prostaglandin estrogen estrogen lipopolysaccharide estrogen short-chain fatty acid estrogen estrogen prostaglandin nimesulide naproxen steroid estrogen progestin estrogen progestin progestin norethisterone acetate estradiol progestin estrogen leuprolide goserelin nafarelin buserelin elagolix leuprolide acetate nafarelin estrogen peptide mineral estrogen estrogen estradiol prostaglandin e2 estrogen estradiol mineral glucose glucose glucose progestin estrogen estradiol progestin levonorgestrel norethisterone glucose desogestrel drospirenone cyproterone acetate levonorgestrel +75 more
organisms 60
microbiota microbiota microbiota microbiota microbiota microbiota microbiota microbiota microbiota microbiota microbiota microbiota microbiota microbiota microbiota noordeloos 2009062 noordeloos 2009062 noordeloos 2009062 noordeloos 2009062 noordeloos 2009062 microbiota microbiota paralactobacillus microbiota paralactobacillus microbiota microbiota rodents noordeloos 2009062 rodents human human microbiota paralactobacillus vpi 3199 vkm:b:574 vkm b-1660 clostridiales bacterium s9 pr-1 vkm:b:574 strain 1535 thermobacterium lactis bacteria stick insect blautia roseburyella ruminococcus unknown eubacterium unknown eubacterium bacteria stick insect microbiota crossopterygii bacteria stick insect crossopterygii mosquito plant microbiota microbiota microbiota microbiota microbiota microbiota microbiota

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