The Gut Microbiota in Perimenopausal Anxiety: A Novel Therapeutic Pathway Through Diet.

Background: Perimenopause is characterized by pronounced fluctuations in ovarian steroids, which are associated with an increase vulnerability to anxiety symptoms. Growing evidence indicates that declining estrogen levels influence gut microbiota composition and microbial metabolic activity, thereby modulating neuroimmune and neuroendocrine pathways involved in emotional regulation. This review explores gut microbiota alterations occurring during the menopausal transition and critically evaluates dietary strategies targeting microbiota-gut-brain mechanisms potentially relevant to perimenopausal anxiety. Methods: A structured literature search was conducted in PubMed, Scopus, and Web of Science to identify clinical, translational, and preclinical studies addressing: (i) gut microbiota changes across perimenopause and menopause; (ii) microbiota-gut-brain pathways implicated in anxiety; and (iii) dietary patterns, nutrients, probiotics, and prebiotics with documented microbiota-modulating effects. The available evidence was synthesized narratively, with particular attention to biological plausibility and clinical relevance. Results: The perimenopause transition is associated with reduced microbial diversity, depletion of Lactobacillus, Bifidobacterium, and short-chain fatty acid (SCFA)-producing taxa, and enrichment of pro-inflammatory microbial signatures. These alterations are linked to increased intestinal permeability, altered tryptophan-kynurenine metabolism, immune activation, and dysregulated hypothalamic-pituitary-adrenal axis activity. Dietary interventions, including Mediterranean-style diets, fiber- and polyphenol-rich foods, fermented products, and selected probiotic and prebiotic formulations, have been shown to modulate gut microbial composition, enhance SCFA production, and attenuate inflammatory and neuroendocrine stress pathways. Preliminary evidence suggests potential anxiolytic benefits; however, randomized controlled trials specifically targeting perimenopausal populations remain limited. Conclusions: Gut microbiota dysbiosis may contribute to anxiety vulnerability in perimenopausal women through interconnected immune, metabolic, and neuroendocrine mechanisms. Dietary modulation of the intestinal microbiota represents a biologically plausible and low-risk complementary approach to support emotional well-being during this transitional period. Well-designed, perimenopause-specific clinical trials are needed to confirm efficacy and inform microbiome-based nutritional strategies.