Microbiota-Host Interactions in Perimenopausal Syndrome: Mechanisms and Therapeutic Strategies (Review).

Background: Perimenopausal syndrome (PMS) is common, with more than 70% of perimenopausal women experiencing symptoms such as hot flashes and anxiety. As a key regulator of host physiology, the gut microbiota may play an important role in the pathogenesis of PMS. Objective: This review aimed to synthesize clinical and preclinical evidence on alterations in the gut microbiota during perimenopause, elucidate the potential mechanisms underlying host-microbiota interactions, and summarize and critically evaluate current therapeutic strategies targeting the gut microbiota. Methods: A targeted literature search of PubMed and Web of Science was conducted for relevant studies published through July 15, 2026. Search terms covered perimenopause, menopause, gut microbiota, estrobolome, gut-brain axis, metabolomics, female microbiome, ovarian function, probiotics, and fecal microbiota transplantation. Human studies were prioritized, with high-quality animal and mechanistic studies included when clinical evidence was limited. Results: Few studies have directly examined women with PMS. Findings on gut microbial diversity and changes in specific taxa have been inconsistent across studies, and no reproducible pattern of gut dysbiosis specific to PMS has been established. Current evidence suggests that ovarian aging and fluctuations in sex hormones may reshape the gut microbial ecosystem. In turn, microbial enzymes and metabolites may interact bidirectionally with host endocrine changes by influencing the enterohepatic circulation of estrogens, immune and inflammatory responses, ovarian function, and gut-brain communication. Lifestyle interventions are supported by a relatively substantial body of evidence for symptom improvement, although whether their effects are mediated by the gut microbiota remains unclear. Certain strain-specific probiotics have shown preliminary clinical promise. However, evidence supporting prebiotics, synbiotics, traditional Chinese medicine, acupuncture, plant-derived products, and fecal microbiota transplantation is derived mainly from small clinical studies or preclinical experiments. By distinguishing direct clinical evidence from PMS populations from indirect evidence derived from other populations and experimental studies, this review reveals a central paradox in current research that strong biological plausibility coexists with insufficient clinical causal evidence. Conclusion: The gut microbiota may contribute to the pathogenesis and progression of PMS through the "gut microbiota-estrogen-ovary-immune-brain axis". However, current evidence primarily supports bidirectional associations and biological plausibility. Although microbiota-targeted interventions have potential therapeutic value, the available evidence remains insufficient to support their routine clinical use. Future research should include longitudinal cohort studies using standardized menopausal staging and multicenter randomized controlled trials. Confounding factors such as age, diet, medication use, and hormone therapy should be adequately controlled. Integrated analyses of multiple omics datasets should also be combined with mechanistic studies to establish the causal role and clinical translational potential of the gut microbiota.