The review, authored by R. S. Rodrigues, P. A. Fontenele, J. C. Rocha, and A. S. Setti, was published on 22 October 2026. The authors conducted a structured PubMed/MEDLINE search covering the database from inception to December 31, 2025, and also screened reference lists of relevant reviews and key primary studies. Evidence was then synthesized thematically across clinical, immunological, and translational domains.

On the clinical side, the review finds that chronic endometritis is associated with infertility and recurrent pregnancy loss, whereas findings in recurrent implantation failure populations are heterogeneous and strongly dependent on the diagnostic criteria used. Mechanistically, the condition is characterized by plasma cell infiltration, pro-inflammatory signaling, and activation of pathways including toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB).

The gut-related component of the proposed axis rests on a separate body of work. Intestinal dysbiosis and barrier dysfunction may permit systemic translocation of microbial products such as lipopolysaccharide, thereby promoting low-grade inflammatory signaling. This mechanism could, in principle, connect gut microbial imbalance to endometrial inflammation, but the review emphasizes a critical evidentiary gap: no direct human study has yet linked gut dysbiosis or endotoxemia to histologically confirmed chronic endometritis within the same cohort.

Because of that gap, the authors caution against treating the axis as an established cause. Chronic endometritis is biologically heterogeneous and may arise from infectious, local microbial, immune-mediated, or systemic-inflammatory mechanisms that can overlap. Reverse causality and shared confounding factors are also plausible explanations for observed associations, meaning that endometrial inflammation could in some scenarios influence the measured microbial or immune markers rather than the reverse.

The review also draws a practical boundary for clinical care. At present, the proposed model does not justify routine microbiome testing or gut-directed treatment for chronic endometritis. Instead, the authors argue, the framework defines priorities for future prospective studies that integrate microbiome profiling, systemic immune markers, and standardized endometrial phenotyping.

For patients and clinicians, the takeaway is that heterogeneous treatment responses and recurrence in chronic endometritis do suggest that broader immunological mechanisms may contribute in selected patients, but the intestinal pathway remains speculative until directly tested in human cohorts. The review’s structured synthesis clarifies what is known, what is inferred, and what remains unproven about the relationship between gut health, systemic inflammation, and the uterine lining in reproductive failure.

Subject of Research: A narrative review of the proposed gut–immune–endometrial axis in chronic endometritis and reproductive failure

Article Title: The Gut–Immune–Endometrial Axis in Reproductive Failure: a Structured Narrative Review of Intestinal Dysbiosis, Systemic Inflammation, and Chronic Endometritis

Article References: Rodrigues, R. S., Fontenele, P. A., Rocha, J. C., & Setti, A. S. (2026). The Gut–Immune–Endometrial Axis in Reproductive Failure: a Structured Narrative Review of Intestinal Dysbiosis, Systemic Inflammation, and Chronic Endometritis. Reproductive Sciences. https://doi.org/10.1007/s43032-026-02182-9

Image Credits: AI Generated

DOI: 10.1007/s43032-026-02182-9

Keywords: chronic endometritis, gut–immune–endometrial axis, intestinal dysbiosis, systemic inflammation, recurrent pregnancy loss, recurrent implantation failure, infertility, lipopolysaccharide, TLR4, NF-κB, endometrium, narrative review