{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:14:46Z","timestamp":1788430486973,"version":"build-2803163510"},"reference-count":134,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Endometriosis is a chronic estrogen-dependent systemic inflammatory disorder characterized by ectopic implantation of endometrial-like tissue, primarily on the ovaries, pelvic peritoneum, and bowel. According to the World Health Organization (WHO) estimate updated in 2025, endometriosis affects approximately 10% (about 190 million) of reproductive-age women worldwide and is a major contributor to chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Standard medical therapies focus on ovarian suppression, which alleviates symptoms but precludes conception and carries significant metabolic and skeletal adverse effects. Recent multi-omics research has raised interest in the gut microbiome and the estrobolome, defined as the microbial gene repertoire involved in estrogen metabolism, as potential modulators of systemic estrogen exposure and immune homeostasis. Altered microbiota composition and microbial \u03b2-glucuronidase activity may influence enterohepatic estrogen recirculation; however, endometriosis-specific evidence is predominantly associative or preclinical and does not establish a causal pathway. Dysbiosis and increased bacterial \u03b2-glucuronidase activity promote enterohepatic recirculation of estrogens, contributing to hyperestrogenism and ectopic lesion proliferation. Concurrently, oxidative stress, peritoneal inflammation, aberrant macrophage polarization, and neoangiogenesis sustain lesion survival and contribute to chronic pelvic pain. This comprehensive review synthesizes mechanistic, preclinical, and clinical evidence regarding microbiome-targeted interventions and nutritional compounds, including probiotics, prebiotics, N-acetyl cysteine (NAC), curcumin, resveratrol, epigallocatechin gallate (EGCG), omega-3 polyunsaturated fatty acids (PUFAs), and vitamin D, in modulating the estrobolome, immune responses, and oxidative microenvironment in endometriosis. We further discuss dietary patterns, bioavailability challenges, and the potential of precision nutrition to optimize reproductive outcomes. These approaches may be considered complementary or investigational adjuncts; current evidence is insufficient to demonstrate disease modification or improvements in spontaneous pregnancy, assisted reproductive technology (ART) outcomes, or live birth. Here, \u201cfertility-sparing\u201d denotes the absence of intentional ovulation suppression rather than proven fertility enhancement.<\/jats:p>","DOI":"10.3390\/nu18172883","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:20:43Z","timestamp":1788427243000},"page":"2883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulating the Estrobolome and Inflammatory Microenvironment in Endometriosis: The Role of Microbiome-Targeted Interventions and Nutritional Compounds"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2375-0472","authenticated-orcid":false,"given":"Stefania","family":"Greco","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2849-4690","authenticated-orcid":false,"given":"Giovanni","family":"Delli Carpini","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-7254","authenticated-orcid":false,"given":"Abel","family":"Dum\u00e9nigo Gonz\u00e0lez","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-8387","authenticated-orcid":false,"given":"Gaia","family":"Goteri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8037-4947","authenticated-orcid":false,"given":"Andrea","family":"Ciavattini","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4400-3786","authenticated-orcid":false,"given":"Pasquapina","family":"Ciarmela","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1056\/NEJMcp1000274","article-title":"Endometriosis","volume":"362","author":"Giudice","year":"2010","journal-title":"N. 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