Microbiota–metabolite axis in endometriosis: Pathogenic mechanisms and clinical implications

Growing evidence highlights the gut, reproductive tract, and endometrial microbiota as important functional contributors in the pathogenesis of endometriosis (EM). Studies have revealed a characteristic microbial imbalance in patients with EM, marked by a reduced abundance of beneficial bacteria and an enrichment of opportunistic pathogens. These microbial communities are thought to influence disease progression primarily through metabolic activity, as demonstrated by metabolomic studies showing their capacity to modulate host immune and endocrine responses. This imbalance may contribute to several key metabolic disturbances, including decreased levels of short-chain fatty acids, particularly butyrate; a shift in tryptophan metabolism toward the kynurenine pathway; elevated β-glucuronidase activity; increased lipopolysaccharide production; and altered secondary bile acid profiles. Functionally, these metabolic alterations are thought to contribute to EM by disrupting immune homeostasis, enhancing estrogen signaling, and driving systemic inflammation, thereby creating a permissive microenvironment for ectopic lesion growth and invasion. Targeted interventions, such as probiotics, high-fiber dietary strategies, fecal microbiota transplantation, and selective modulation of microbial or host metabolic enzymes, are emerging as promising non-hormonal therapeutic approaches. Nonetheless, further studies incorporating longitudinal cohort designs and integrative multi-omics approaches are essential to establish causality and facilitate the development of precise diagnostic and personalized treatment strategies.