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

Chronic endometritis (CE) is a persistent inflammatory condition of the endometrium characterized by stromal plasma cell infiltration and is increasingly recognized in women with infertility, recurrent implantation failure (RIF), and recurrent pregnancy loss (RPL). Although traditionally considered a localized infectious process, heterogeneous treatment responses and recurrence suggest that broader immunological mechanisms may contribute in selected patients. This structured narrative review synthesizes clinical and mechanistic evidence relevant to a possible gut-immune-endometrial axis. A structured PubMed/MEDLINE search was conducted from database inception to December 31, 2025, and reference lists of relevant reviews and key primary studies were screened. Evidence was synthesized thematically across clinical, immunological, and translational domains. CE is associated with infertility and RPL, whereas findings in RIF populations are heterogeneous and strongly dependent on diagnostic criteria. CE is characterized by plasma cell infiltration, pro-inflammatory signaling, and activation of pathways including toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB). Separately, intestinal dysbiosis and barrier dysfunction may permit systemic translocation of microbial products such as lipopolysaccharide, thereby promoting low-grade inflammatory signaling. However, no direct human study has yet linked gut dysbiosis or endotoxemia to histologically confirmed CE within the same cohort. The proposed axis should therefore be regarded as a hypothesis-generating framework rather than an established causal pathway. CE 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. At present, the model does not justify routine microbiome testing or gut-directed treatment for CE, but it defines priorities for prospective studies integrating microbiome profiling, systemic immune markers, and standardized endometrial phenotyping.