The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis Original paper

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  • Karen Pendergrass ID
    Karen Pendergrass

    User avatarKaren Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.

May 24, 2025

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  • Endometriosis
    Endometriosis

    Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.

Researched by:

  • Karen Pendergrass ID
    Karen Pendergrass

    User avatarKaren Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.

Last Updated: 2025

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Karen Pendergrass

Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.

What was studied?

This study investigated the role of lactoferrin (LF) in relation to iron metabolism in women with and without endometriosis by measuring levels of LF, ferritin (FT), transferrin (TF), and iron (Fe) simultaneously in plasma and peritoneal fluid. The authors specifically explored whether the concentrations and ratios of these iron-related proteins in the two biological compartments could distinguish the presence and progression of endometriosis. The goal was to identify noninvasive or minimally invasive biomarkers that may aid in diagnosing or staging the disease based on iron metabolism, especially given endometriosis’ pro-inflammatory, iron-rich microenvironment.

Who was studied?

The study cohort included 90 women of reproductive age undergoing diagnostic laparoscopy, of whom 57 had histologically confirmed endometriosis (stages I–IV) and 33 did not. Plasma and peritoneal fluid samples were collected pre- and intra-operatively. Subjects were classified based on endometriosis diagnosis and stage, and specimens were evaluated for levels of LF, FT, TF, and Fe using ELISA, immunoturbidimetric assay, and colorimetric methods.

What were the most important findings?

Key findings highlight that ferritin and iron concentrations were significantly elevated in peritoneal fluid compared to plasma, especially in patients with advanced-stage endometriosis. In contrast, transferrin was consistently lower in peritoneal fluid. Notably, lactoferrin levels did not significantly differ between women with and without endometriosis when evaluated independently in plasma or peritoneal fluid, but the peritoneal fluid/plasma lactoferrin ratio decreased progressively with increasing disease severity, significantly distinguishing stage I from stage IV. The ferritin ratio was markedly higher in the endometriosis group, underscoring its potential as a disease marker. Correlation analyses revealed that in severe endometriosis, lactoferrin was significantly associated with ferritin and iron in the peritoneal fluid, suggesting a disrupted iron regulation mechanism localized to the disease microenvironment. Importantly, the elevated ferritin concentrations in peritoneal fluid may serve a compensatory, protective role to sequester iron and mitigate oxidative stress, while lactoferrin may lose this protective function as disease progresses.

From a microbiome perspective, this study underscores the iron-dependent ecological shifts that may select for siderophilic pathobionts. The iron overload and pro-oxidative milieu likely fosters the expansion of iron-requiring microbial taxa, potentially including Escherichia, Enterobacter, and Fusobacterium, known to be enriched in some endometriosis microbiome signatures. While microbial profiling was not performed, the metallomic dysregulation described supports the hypothesis that iron availability is a crucial factor in shaping pathogenic microbial communities in endometriosis.

What are the greatest implications of this study?

This study provides compelling evidence that iron-binding proteins—particularly ferritin and lactoferrin—play a localized and differential role in the progression of endometriosis. The findings suggest that peritoneal fluid iron metabolism, and especially the ferritin-to-lactoferrin balance, may be a critical axis of disease progression and potentially a therapeutic target. The study introduces the peritoneal fluid/plasma concentration ratio as a novel diagnostic parameter, offering a more granular assessment than conventional plasma markers. The declining lactoferrin ratio and increasing ferritin ratio with disease severity may signal a transition from iron sequestration and immune modulation toward iron-driven oxidative stress and tissue damage. This may serve as a foundation for the development of metallome-targeted diagnostics and therapies, including exogenous lactoferrin supplementation, which the authors suggest could restore iron balance in advanced disease stages. These findings also have implications for understanding how iron dysregulation may foster microbial dysbiosis, providing a mechanistic link between host iron metabolism and the pathophysiological selection of microbial communities in endometriosis.

Lactoferrin

Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein classified as a postbiotic with immunomodulatory, antimicrobial, and prebiotic-like properties.

Endometriosis

Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.

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