Modulating the Estrobolome and Inflammatory Microenvironment in Endometriosis: The Role of Microbiome-Targeted Interventions and Nutritional Compounds

Stefania Greco, Giovanni Delli Carpini, Abel Duménigo González, Gaia Goteri, Andrea Ciavattini, Pasquapina Ciarmela
Nutrients · 2026 · vol. 18(17) , pp. 2883 · doi:10.3390/nu18172883 · PMID:42739055 · W7207773598
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This review synthesizes evidence on microbiome-targeted interventions and nutritional compounds for modulating the estrobolome and inflammatory microenvironment in endometriosis, noting insufficient data to confirm disease modification or improved reproductive outcomes.

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Abstract

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 β-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 β-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, "fertility-sparing" denotes the absence of intentional ovulation suppression rather than proven fertility enhancement.

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MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood (2-hop)

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. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (100)

SciLite annotations

chemicals 103
estrogen estrogen estrogen estrone cysteine curcumin resveratrol catechin omega-3 fatty acid vitamin d estrogen progesterone prostaglandin progestin estrogen mineral estrone estrogen polyphenol omega-3 fatty acid vitamin d estrogen estrogen estrogen estrogen polyunsaturated fatty acid inulin fructooligosaccharide galactooligosaccharide short-chain fatty acid acetate propionate butyrate butyrate butyrate inulin acetyl n-acetyl zonisamide amino acid l-cysteine glutathione iron curcumin polyphenol curcumin prostaglandin e2 curcumin curcumin curcumin curcumin curcumin nanoparticle dienogest resveratrol trihydroxyanthraquinone polyphenol diethylstilbestrol resveratrol estrogen resveratrol +43 more
organisms 32
microbiota noordeloos 2009062 noordeloos 2009062 noordeloos 2009062 rodents human unknown eubacterium paralactobacillus tissieria paralactobacillus rodents human human urospermum dalechampii stenanthemum gracilipes senecio condylus urospermum dalechampii turmeric viteus vitifoliae stachytarpheta jamaicensis thea sinensis crossopterygii noordeloos 2009062 zitter rats human human human microbiota paralactobacillus paralactobacillus rodents noordeloos 2009062

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